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On Wednesday night in Waco, Texas, the 2019 Division I national champion Baylor Lady Bears and the 2019 Division II national champion Lubbock Christian Lady Chaps face off in an exhibition game. Itll also be a family affair, as Baylor senior Lauren Cox takes the court against her younger sister, LCU freshman Whitney Cox.

But its also much more than a high-profile exhibition more than basketball, even.

Wednesday night is Baylors fourth annual Type 1 Diabetes Awareness Game. And in case youre doing some math in your head, yes, this is Laurens fourth season at Baylor.

My freshman year, Coach [Kim] Mulkey was really interested in my diabetes, she wanted to see my insulin pump, she wanted me to watch me test my blood sugar, Lauren told High Post Hoops. And it was kind of her idea, like, lets do a Type 1 awareness game.

Type 1 diabetes is a condition where the pancreas has trouble producing insulin, the hormone that lets glucose be used to produce energy. It typically develops in children and adolescents Lauren was seven years old when she was diagnosed.

Her sister Whitney, on the other hand, was a junior in high school when she learned she also had Type 1. She told High Post Hoops that after she came home from the hospital after her diagnosis, Lauren came home to surprise her.

We just kind of sat there, like hugging and crying, Whitney said. She just knew what I was going to be going through. She just gets it.

I think me being able to be there for her when she was first diagnosed, I think that was really important, just to show her that she can still do whatever she wants to do, Lauren said.

Type 1 diabetes can be very manageable, and both sisters take advantage of the latest medical technology to ensure it doesnt affect their game. They wear continuous glucose monitors and insulin pumps, and both devices work in tandem to avoid any issues on the court.

Having the new technology helps a ton, just making it so much more convenient, Whitney said. She and the teams trainer use an app on their phones to keep track of her blood sugar level.

Lauren felt the same way, saying the technology she uses hasdefinitely made life a whole lot easier for me, and for my trainers.

Baylor put on its first Type 1 Awareness Game in January 2017. Not much has changed since, aside from moving the game to the fall its a simple opportunity for diabetic fans to interact with someone succeeding at a high level while managing her condition. Type 1 fans will sit together during the games, then meet Lauren after.

And, this season, Whitney.

Its really special [sharing this years game with her], Lauren said. Whitney hasnt been diabetic for long, but it still means a lot that they were willing to work it out to get [LCU] here for a game, and to make it the Type 1 game, so its gonna be a really special night.

Lauren is coming up on four years of using her platform at Baylor to spread awareness of Type 1 diabetes, and Whitney, a freshman, hopes to follow in her footsteps.

In addition to wanting to start a Type 1 awareness game at LCU, in her first couple of weeks on campus, she participated in a health fair where she had the opportunity to talk about her diabetes.

They had a diabetic brunch that I spoke at, just kind of explaining day-to-day operations of being a diabetic, pretty much, Whitney said. That was the very first time I actually kind of spoke out about it. So that was pretty cool. I definitely hope to do some more things like that around campus, as well as in the basketball world.

The sisters have only faced off in a competitive game once they were on different club teams within the same organization when Lauren was in high school and met in a tournament championship game. But with the exhibition tag attached to Wednesdays game, the competition wont be the important part this time.

TAMPA, FL APRIL 05: Oregon forward Oti Gildon (32) guards Baylor forward Lauren Cox (15) in 2019 NCAA Womens National Semifinal Game One between the Oregon Ducks and the Baylor Bears at at Amelie Arena in Tampa, FL on on April 5. (Photo by Mary Holt/Icon Sportswire via Getty Images)

I think itsjust gonna be fun, Lauren said. Just because we have so many family and friends coming to that game, and everyones really excited. They got split shirts made that have the BU and the LCU colors on opposite sides and all that. Yeah, its just gonna be really fun and kind of our last time ever on the same court again.

Whitney expressed a similar sentiment at playing her first two collegiate games against two of Texas best teams (LCU visited Texas for an exhibition on Monday night).

My coach actually asked me earlier this week if I was nervous for any of it. And I told him, not at all, Whitney said. Im really excited for it.

When asked what they want people to know about being a diabetic athlete, the sisters answers were almost identical.

It cant stop you from doing whatever you want to do, Lauren said. As long as you stay on top of it and control it, then youre going to be perfectly fine and you can do anything that you set your mind to.

It doesnt stop you from doing anything, Whitney said. Its completely manageable. And its just another thing you have to take care of. At the end of the day, you can still do whatever you want to do.

Baylor hosts Lubbock Christian on Wednesday, Oct. 30, at 7 p.m. CT. The game wont be televised, but you can listen to it on Oldies 97.7 FM or follow the live stats.

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Its just gonna be really fun: Cox sisters to face off in Baylors Type 1 Diabetes Awareness Game - High Post Hoops

ATKINSON The Atkinson Lions, in partnership with the Salem Lions, will be offering free diabetes testing (A1C) on Nov. 13.

The testing will be done on a first-come, first-served basis from 4 to 7 p.m. at the Atkinson Community Center on 4 Main St.

The Lions will bring in health professionals to do the A1C testing and will also bring in a nutritionist to provide information on nutrition to the public.

The diabetes A1C test measures the average blood sugar level over the past two to three months.

Its like a memory of your blood sugar levels and shows how well your body is controlling your blood sugar levels over time, the Lions said in a news release.

The American Diabetes Association recommends an A1C level of 5.7% or less.

If you test higher than this level, you will be advised to see your primary care doctor, the news release states. Note that all information will be kept strictly confidential. The test takes about five minutes to provide results.

Fasting is not required for the A1C test.

By some accounts, 1 in 4 Americans do not know they have pre-diabetes or diabetes. Complications include eye disease, cardiovascular disease, kidney disease, nerve damage, pregnancy complications, and amputations.

Free information concerning diabetes and diabetic-appropriate refreshments will be on hand at the event.

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Free A1C diabetes testing offered in Atkinson | Health - The Union Leader

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Alzheimers disease and type 2 diabetes could be linked in ways were only beginning understand, according to scientists presenting the latest research findings at Neuroscience 2019, the annual meeting of the Society for Neuroscience. Untangling the connection could lead to earlier Alzheimers diagnosis and better treatments for both diseases.

The crux of the connection is how the brain metabolizes its energy sourceblood glucose (aka blood sugar)and the variety of factors that influence that process, including diet, sleep, and cardiovascular health.

Not much is known about the connection between dementia and the metabolic system that fuels the brain, said panel moderator David Holtzman, MD, a professor at Washington University and scientific director of the Hope Center for Neurological Disorders. Further research can help us understand how to manipulate these functions for treatment purposes, as well as better identify the underpinnings of the disease.

Researchers presented findings approaching the problem from several angles.

Sami Gabbouj, a researcher from the University of Eastern Finland, discussed a study showing that the typical Western diet, high in fat and carbohydrates, leads to decreased brain insulin signaling and eventually impaired memory in mice genetically prone to Alzheimers. Insulin signaling is key to how the brain monitors and manages insulin release to balance blood sugar. Previous research has found a link between damaged insulin signaling and the development of Alzheimer's.

The typical western diet made worse age-related memory impairment in the mice, Gabbouj said.

The results suggest the possibility that the Western diet may handicap the brains energy metabolism and serve as a trigger for worsening memory in those genetically predisposed to Alzheimers.

Steven W. Barger, PhD, from the University of Arkansas for Medical Sciences, presented research showing that Alzheimers disease mimics diabetes by impairing how the brain metabolizes blood sugar. By examining mice genetically altered to develop Alzheimer's, researchers observed that a flaw in glucose delivery to neurons leaves extra glucose in the blood.

Alzheimers mice show diabetes traits on a normal diet, [with the] same physical activity levels and same feeding habits, Barger added. The findings shed light on why human Alzheimers patients often have higher blood sugar levels, and further confirm a link between the diseases.

Sleep research has also revealed connections between blood glucose metabolism and Alzheimers.A study presented by Shannon L. Macauley, PhD, from the Wake Forest School of Medicine, showed that glucose resistance and abnormal sleep patterns are prevalent in Alzheimers [predisposed] mice prior to the appearance of any other disease symptoms, such as cognitive decline.

This research points to the early role sleep loss seems to play in the development of Alzheimers, and suggests that poor sleep combined with type 2 diabetes may be especially dangerous for those at genetic risk for dementia.

The researchers were careful to note that the cause and effect across all of these studies isnt entirely clear. We dont yet know whether diabetes is a precursor to Alzheimers or if impaired blood sugar metabolism is a side-effect of Alzheimers. Its just too early to know either way. Ultimately we may find that both are true. And since much of the research to-date relies on animal models, were also not sure how closely these results will translate in humans.

What we do have is a strong starting point for understanding the link between these diseases that affect millions, and that may eventually lead to improved diagnosis and treatments.

Research was presented at Neuroscience 2019, the annual meeting of the Society for Neuroscience in Chicago. Studies are considered preliminary prior to being published.

Read more from the original source:
Untangling The Link Between Alzheimers Disease And Diabetes: What The Latest Science Tells Us - Forbes

November is National Diabetes Month, with World Diabetes Day on Nov. 14.

Conemaugh Health System encourages all individuals to learn more about diabetes and potential symptoms that could point to a problem.

More than 30 million Americans have diabetes, and 84 million adults have prediabetes, according to the Centers for Disease Control and Prevention. Diabetes is the seventh-leading cause of death in the United States.

Diabetes is a medical condition in which the body does not make insulin or has a reduced response to insulin, causing sugar levels to be too high. Symptoms of diabetes including urinating often, blurry vision, being very thirsty, losing weight unexpectedly, being very hungry, experiencing more fatigue than usual, and being irritable.

Individuals at risk for diabetes or pre-diabetes include being over 45 years of age, having high blood pressure, being overweight, low physical activity, family history of diabetes or history of diabetes during pregnancy.

While people with diabetes can exhibit noticeable symptoms, most patients diagnosed with type 2 diabetes do not show overt warning signs that they have developed the disease.Unfortunately, many do not know they have diabetes until they have developed one or more of its serious complications.

Conemaugh Diabetes Institute provides extensive education and support services to patients diagnosed with diabetes and individuals at risk for developing diabetes.

Staff members of the institute work with family members and primary care physicians to coordinate an effective plan of care for each patient. Individual and group education and appointments are available.

Conemaughs education programs are recognized by the American Diabetes Association and are led by Certified Diabetes Educators including registered nurses, registered dietitians, and additional healthcare professionals.

One of the key components of preventing and managing diabetes is following a healthy meal plan that focuses on achieving good nutrition, said Ashley Staruch, registered dietitian at the Conemaugh Diabetes Institute and Certified Diabetes Educator. Its not about following a fad diet that is popular at the current moment. Its about finding the right balance between eating the foods we enjoy and maintaining optimal blood-sugar control. Quality of life is such an integral part of healthy nutrition.

All foods, in moderation, can fit into a healthy meal plan.

Education for diabetes patients includes understanding healthy and unhealthy food options, meal planning, reading food labels, tips for grocery shopping, the best options when eating out and how to make the foods they enjoy fit into their daily meal plan.

We show patients that diabetes is manageable and they can still eat great tasting foods, Staruch said.

Its about balance and finding the healthiest ingredients for meals they are preparing. Once they experience small successes of seeing their blood sugars improve, feeling great and having more energy, it makes sustaining the healthy lifestyle easier.

One main concern for a person with diabetes is carbohydrates, which come primarily from starch, fruit and milk.

Carbohydrates are broken down into sugar by an individuals digestive system and cause an increase in blood glucose.

The more carbohydrates eaten, the higher the patients blood sugar.

A person with diabetes should focus on consuming healthy sources of carbohydrate found in fruit, vegetables, whole grains, beans and low-fat milk.

Foods that should be limited are those that provide calories, but have little nutritional value. These foods include sugary beverages such as soda and juice, sweetened breakfast cereals, desserts and snack foods.

Its important to be aware of the foods we are eating and to keep track of what goes into our bodies, Staruch said.

Eating too many calories, specifically too many calories from carbohydrates, can cause the blood sugar level to significantly increase.

We need to focus on choosing healthy options, especially when it comes to carbohydrates.

Patients that appropriately manage diabetes and their blood sugar levels can lead normal lifestyles with limited or no complications. However, uncontrolled or unmanaged diabetes can lead to serious, irreversible long-term health conditions such as damage to blood vessels in the heart, brain, legs, eyes, kidneys, feet and nervous system.

Prevention and management are key, Staruch said. Whether trying to prevent diabetes or manage diabetes, we can help patients get back on track and enjoy their daily lives.

Diabetes meal planning tips and related informationare available on the CDC website at CDC.gov, and the American Diabetes Association at diabetes.org.

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Family Life | Health tips: Know the risks of diabetes and follow a healthy meal plan - TribDem.com

For many, including myself, this syndrome is an invisible but real burden. For some, it is even a disability. When we are forced to live out of sync with our internal clocks, our health suffers. The mismatch between internal time and environmental time has been linked to problems including depression, diabetes, obesity and poor cardiovascular health. Our immune systems become a mess. Many night-shift workers have similar problems; for us, a traditional 9-to-5 schedule is the equivalent of night-shift work.

This happens because, even if we force ourselves to wake up early, our metabolism is not ready to perform simple tasks such as properly digesting a meal, for example we do not produce as much insulin in the morning as normal people do. Our core body temperature also follows an internal rhythm, producing sleepiness or alertness much later. This is true as well for the release of cortisol, melatonin and other hormones essential to the sleep-wake cycle. In the morning, our eyes might be open, but, for all intents and purposes, we are still sleeping.

And its no use getting exhausted and deliberately undersleeping with the intention of falling asleep early the next day a recommendation Ive heard a lot, including from doctors. Circadian rhythms operate independently of the sleep-pressure system. This is the case even among normal people: Even if you slept miserably last night and woke up very early, it is unlikely that youll fall asleep at 6 p.m.; thats because your circadian rhythms are cycling on as usual, unaffected by your lack of sleep. Your attempt to hit the sack would clash with something called the wake-maintenance zone, a three- to four-hour interval of maximum physiological alertness. (In normal sleepers, it occurs from 6 p.m. to 9 p.m.)

Delayed sleep phase syndrome has a genetic basis, as my own unscientific sample demonstrates: My mom also has it, though her case is not so extreme. Apart from that, other mechanisms can account for the disorder. Some studies indicate that our built-in circadian period might be unusually long (say, 25 hours instead of 24); others find dysfunction in our homeostatic sleep drive, a reduced response to the phase-resetting effects of daylight, or an excessive response to the sleep-delaying effects of artificial evening light. There is, as of yet, no cure only short-term fixes that include the use of a light therapy box and the administration of well-timed melatonin pills. But in the long run, most of us fail to adapt.

Heres the thing, though. If left to our own devices if allowed to follow our own biological clocks we sleep just fine.

Individuals with extreme cases of the syndrome are unable to work conventional jobs. We are also famously unreliable at keeping appointments and participating in diurnal social activities. We learn to make excuses and tell lies. I often say that I work nights, which is true its just not the whole story. Most people respect work-related excuses, but sneer at health conditions theyve never heard of.

Thats the worst thing about having a circadian rhythm disorder: living in a society that places a moral value on the time your alarm clock goes off. Most cultures emphatically equate early rising with righteousness: As we say in Brazil, God helps those who wake up early.

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Early to Bed, Early to Rise Makes Me Exhausted, Depressed and Sick - The New York Times

Type 2 diabetes is a condition in which the body cant control the amount of glucose in the blood. The body doesnt respond to insulin properly and may not produce enough, causing a person's blood sugar levels to become too high. If blood glucose isnt controlled properly and stays too high, it can lead to a number of serious health problems, including kidney failure, nerve damage, heart disease and stroke.

Regularly eating a poor diet can increase your risk of developing type 2 diabetes, but diet can also play a part in lowering and controlling blood sugar.

Experts say theres nothing you cannot eat if you have type 2 diabetes, but certain foods should be limited.

As some general rules, the NHS advises eating a wide range of foods - including fruit, vegetables and some starchy foods like pasta.

Sugar, fat and salt should also be kept to a minimum, and its important to eat breakfast, lunch and dinner every day and not to skip meals.

READ MORE: Type 2 diabetes: Best fruit to include in your breakfast to lower blood sugar

But certain food and drink have also been found to hold blood sugar lowering properties, and when it comes to the first meal of the day, breakfast, one food proven to have a positive impact on blood sugar levels is eggs.

According to a 2015 study in men aged between 42 and 60 years, those who ate the most eggs were 38 percent less likely to develop type 2 diabetes than those who ate the fewest eggs.

The explanation for this may be that eggs provide essential nutrients that can benefit overall health, and can help replace higher-carb or more processed breakfast choices.

Another study found participants who ate two eggs a day for 12 weeks saw a significant reduction in their body fat and body mass index (BMI) compared with those who ate no eggs during this period.

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Excessive egg consumption should be avoided as research suggests eating a high number of eggs may raise the risk of developing type 2 diabetes and heart disease.

While the connection isnt clear, researchers believe excessive cholesterol intake, when it comes from animal foods, may increase those risks.

Eggs are high in cholesterol, but whether or not this negatively effects the body is still being debated.

If you have type 2 diabetes and find it hard to change your diet, a dietician may be able to help.

Read more:
Type 2 diabetes: Eating this food for breakfast could lower blood sugar - Express

I do think the data are so clear about what this benefit can be, said Matt Longjohn, the former chief medical officer of the Y, whose pilots of the diabetes prevention program established the benefits of the program for CMS actuaries. Longjohn, who ran for the House of Representatives as a Democrat from Michigan last year, said it seems like regulators are making decisions that are penny-wise and pound-foolish.

The program, approved late in the Obama administration and carried out in the Trump era, targets patients on the verge of developing diabetes. It provides weight loss training and education proven methods of prevention. Rules set in 2017 projected widespread popularity for the benefit, estimating that between 50,000 and 110,000 people would take advantage of it each year from 2018 to 2027. The resulting weight loss and fewer cases of type 2 diabetes would improve health and lower Medicare health care spending by $182 million during that period, the agency estimated.

But the first year of the program appears to have fallen dramatically short of the agencys estimates: Claims data from the Centers for Medicare and Medicaid Services for 2018 shows that only 202 people used the program, according to an analysis conducted exclusively for POLITICO by open data startup CareJourney, which has access to the agencys chronic care claims database. The pace has accelerated somewhat in the first quarter of 2019, with 396 using the service.

The statistics come with some caveats suggesting they may underestimate the true numbers of Medicare beneficiaries using the program. They dont include Medicare Advantage beneficiaries and dont reflect lags in paid claims. Some providers have said CMSs contractors have been slow to pay claims as they adjust to the new program; for example, the Y, which includes YMCAs nationwide, told POLITICO that claims submitted in 2018 still havent been paid.

CMS would neither confirm nor deny the figures and said its data would not be complete until 2020. It did not answer other questions about its implementation of the program.

But the paltry figures come as a disappointment to the diabetes prevention programs most vocal advocates. The American Medical Association, for example, says half of all Medicare beneficiaries have prediabetes, and has argued that CMS action would be helpful in promoting the success of the new benefit.

The benefit has added challenges as suppliers include community-based organizations that need training in applying and billing Medicare, said the associations president, Patrice Harris, in a statement.

The timing of the new benefit introduced at the end of the Obama administration may have slowed its impact. HHS had a huge amount of turnover from folks who understood the benefit, the rationale, the cost-saving and life-saving benefits, said Matt Longjohn.

Longjohn says he believes Trump administration officials appreciate the program, but I think they got caught flatfooted. I think they had a couple bureaucratic false starts, he said.

He attributed the slow growth of the program to a lack of providers and a lack of promotion that might have stoked demand for the services of the 600 program providers thus far authorized by CMS.

But the figure obscures significant holes in the network. Ten states have zero providers, said Brenda Schmidt, the CEO of Solera Health, a network of diabetes prevention and social providers. Many major metropolitan areas have few or no providers: Dallas has no providers within a 100-mile radius, according to CMSs provider finder, to take one example. The closest providers for a Philadelphian might well be a thirty-mile schlep to Wilmington, Del.; a Washington resident might need to go to Baltimore.

The lack of providers can be traced back to a pair of CMS decisions restricting supply. The agency has not yet authorized digital providers, and imposes numerous regulations on bricks-and-mortar-based providers to prevent fraud. The latter have been medicalized, Schmidt said, saddled with regulations befitting medical doctors.

Providers have to run a gauntlet of requirements, including gathering the Social Security numbers of all board members, hiring a full-time privacy director, conducting penetration to test their organizations cybersecurity and building IT infrastructure to handle billing, Schmidt and the Ys Heather Hodge said. Complying with just one of those requirements penetration testing can cost $30,000, Schmidt said.

Non-profits just throw up their hands, said Longjohn, whos been consulting with providers on CMS requirements. The cost of keeping up with regulatory requirements leads them to leave the market. Pharmacies and supermarkets showed interest at one point but have opted out of the program, Schmidt said.

Twenty Y locations are qualified to provide diabetes prevention program services to Medicare recipients, said Hodge, the Ys lead on the program. But none, so far, have broken even, she said.

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Researchers have come to similar conclusions about the programs economics. In 2018, two studies examining programs based in Denver and the Bronx concluded that Medicares proposed reimbursements were hundreds of dollars per beneficiary lower than the costs of running the program.

Meanwhile, the agency has also shut out a class of startups seeking to offer a digital version of the program. Numerous companies like Omada Health, Livongo, Canary Health, and Noom offer virtual prevention programs that have won over private payers and employers. But Medicare hasnt even agreed to a demonstration model to test their products.

No progress, Canary health co-founder Neal Kaufman said of Medicares interest.

Interest groups have tried to convince the agency: in May 2018, the AMA sent a letter to Adam Boehler, then director of CMSs innovation center, arguing that a demonstration of virtual diabetes prevention, or DPP, would be helpful. That letter was followed by comments on two subsequent rules pushing virtual DPP in both traditional Medicare and Medicare Advantage. The main goal of allowing virtual DPP in traditional Medicare has proven elusive, however.

Schmidt said her Medicare Advantage clients collectively had hundreds of thousands of beneficiaries who qualify for the benefit, but are unable to use it.

The programs lack of success so far has implications that extend beyond individuals at risk for developing Type 2 diabetes. Although CMS and the private health sector frequently declare their interest in addressing social determinants of health and some state Medicaid programs have started such programs CMSs approach to DPP suggests it may have trouble reimbursing even simple things like pest abatement to lower asthma risks.

If those services get reimbursed, I wouldnt want to see them apply the same standards, said Schmidt.

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Medicare diabetes prevention program helps a few hundred instead of hundreds of thousands - Politico

UniQure has started screening patients for its phase 1/2 trial of gene therapy AMT-130 for Huntingtons disease, and says it hopes to start treating the first subject in late 2019 or early 2020.

The start of the trial will give the Dutch biotech a second gene therapy in clinical trials to go along with AMT-061 (etranacogene dezaparvovec), its one-shot therapy for haemophilia B which is in phase 3 testing.

Huntingtons disease is a rare, devastating neurodegenerative genetic disorder that affects motor function and causes severe cognitive decline, eventually leading to total physical and mental deterioration.

The disease is caused by a mutation in the gene coding for huntingtin which causes the formation of an abnormally long and unstable form of the protein that is chopped up by cellular repair mechanisms into smaller, toxic fragments.

AMT-130 consists of an adeno-associated virus (AAV) vector carrying a micro-RNA that is designed to switch off the huntingtin gene and prevent it from producing the mutant form of the protein.

In annual models, a single dose of AMT-130 was shown to reduce huntingtin levels, initially in deep structures of the brain like the striatum that are affected first by the disease and spreading to higher structures such as the cerebral cortex that come into play later in the course of Huntingtons.

The phase 1/2 trial will be conducted in around 26 patients at several clinical sites, who will be treated either with a single dose of the gene therapy directly into the striatum or an imitation procedure with no drug.

The main outcome measures will be safety and the persistence of AMT-130 in the brain, but the trial will look at clinical outcomes including motor, cognition, and behavioural function over a five-year period. First results should be available in 2022.

Other companies notably Wave Life Sciences/Takeda and Ionis/Roche are developing antisense drugs to switch off production of huntingtin, but these would require continuous dosing in order to be effective.

The announcement was made in UniQures third-quarter results update, at which it also said it had completed enrolment of 62 patients into its HOPE-B trial of haemophilia B therapy AMT-061, setting it on course for a readout in 2020 and possible filing in early 2021.

In July, UniQure reported phase 2b results with AMT-061 showing that it could restore Factor IX levels into the normal range for two out of three subjects.

UniQure was the first company to launch a gene therapy onto the market in Europe, introducing Glybera (alipogene tiparvovec) for familial lipoprotein lipase deficiency (LPLD) in 2012, but the product was a commercial flop and was withdrawn from sale in 2017.

Read more from the original source:
UniQure presses go on Huntington's gene therapy trial - - pharmaphorum

PTC Therapeutics gene therapy candidate PTC-AADC (formerly AGIL-AADC) provided clinically meaningful and sustained improvements in motor, cognitive, and language milestones in children with aromaticl-amino acid decarboxylase (AADC) deficiency up to five years following the one-time treatment, trial analyses show.

A single dose of PTC-AADC delivered into the brain lowered the number of oculogyric crises (involuntary upward eye movement) and recovered childrens weight, as well as improved their ability to sit, walk, and talk over a five-year period.

PTC Therapeutics will request marketing approval soon, with plans to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration later this year.

The new findings were shared at the 48th Annual Meeting of the Child Neurology Society (CNS), held recently inCharlotte, NC. Data were presented in two posters titled AGIL-AADC gene therapy results in sustained improvements in motor and developmental milestones through 5 years in children with AADC deficiency (page S136), and Safety and Improved Efficacy Outcomes in Children With AADC Deficiency Treated with AGIL-AADC Gene Therapy: Results From Three Clinical Trials (page S148).

We are excited to see the transformational effects in AADC deficiency patients in this long-term study as patients with severe AADC deficiency never achieve the ability to sit, walk or talk, Stuart Peltz, PhD, PTC Therapeutics CEO, said in a news release.

We are on track to submit a BLA to the FDA by the end of the year and are proud to be on the verge of bringing the first commercial treatment for AADC deficiency patients which is in line with our mission of bringing clinically differentiated treatments to patients with rare disorders, he added.

PTC-AADC is an investigationalgene therapy designed to deliver a healthy copy of the DDCgene the faulty gene in patients with AADC deficiency to nerve cells. The goal is to restore the production of AADC enzyme which is missing because of this genetic defect and counter the symptoms caused by this deficiency.

A working copy of DDC is passed on to cells through an adeno-associated virus that is modified to be non-infectious.

The gene therapy is injected via a surgical procedure into an area of the brain called the putamen. This region is crucial for producing chemical messengers (neurotransmitters) such as dopamine and serotonin, which are involved in movement control but fail to be produced in patients with the disease.

In one of its presentations, PTC Therapeutics provided the most extensive study of PTC-AADCs efficacy and safety to date. It conducted a joint analysis of three open-label clinical trials, which together enrolled 26 children with AADC deficiency, ranging in age from 21 months to 8.5 years.

At the beginning of these studies, children had no full head control and were unable to sit, stand, or walk. They were given a single dose of PTC-AADC (total dose, 1.81011 vector genomes, vg) which was injected into the patients putamen during a single surgery session.

One year after treatment, the patients mean body weight had increased from 12.0 kg to 15.2 kg, and there was a reduction in the frequency of involuntary upward eye movements characteristic of the disease (oculogyric crises).

Dyskinesia (uncontrolled erratic movements) was a common adverse event, affecting 23 of 26 patients, but most events were mild or moderate in severity, and all cases had resolved within 10 months from dosing.

In addition to failing to reach key developmental milestones, such as walking and talking, children with AADC deficiency can experience severe symptoms that affect their everyday lives. These symptoms can include episodes of oculogyric crises, which can last for minutes or hours and involve sustained upward movement of the eyes, involuntary movements of the neck, tongue protrusions and jaw spasms, which can be very distressing for patients and their families, said Claudio Santos, MD, senior vice president of global medical affairs at PTC Therapeutics.

The post-treatment data presented at CNS confirm reductions in the number of patients experiencing oculogyric crises, suggesting that this gene therapy treatment has the potential to make a real difference in the lives of patients with AADC deficiency, he added.

A second analysis demonstrated that PTC-AADCs benefits can hold up to five years after treatment, the longest data available for any investigational therapy for AADC deficiency.

The findings came from the latest follow-up data of two open-label clinical studies: AADC-1601 (NCT02926066), a trial in which patients were enrolled under individual compassionate use consents, and AADC-010 (NCT01395641).

Together, the studies enrolled 18 patients who were 21 months to 8.5 years old. None had full head control or could sit unassisted or stand. In this update, all patients had two years of follow-up data, and eight of these patients had five years of post-treatment data.

Prior results shared by PTC Therapeutics showed that at two years, eight patients (44%) had achieved full head control, six (35%) were able to sit unassisted, and three (17%) could stand without support. Among the eight patients followed for five or more years, four (50%) had full head control, four (50%) could sit unassisted, and two (25%) could stand without support.

The latest results continue to support these meaningful improvements in motor, cognitive, and language skills, and importantly, show that effects from a single dose of PTC-AADC can last at least five years post-treatment.

In addition, all treated patients continued to demonstrate sustained production of dopamine in the body, one of the neurotransmitters missing in patients with AADC deficiency.

No new safety signals were observed during these long-term evaluations.

Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.

Continued here:
AADC Improvements Sustained with Gene Therapy PTC-AADC, Data Say - AADC News

It's a very early report, from just two patients, only a few months after treatment. But UMass Medical School Dean Terence Flotte this week shared at a conference what could be landmark news about a terrible genetic disease: Two young patients with Tay-Sachs disease showed no ill effects from a new gene therapy that aims to correct the defect at the heart of the disease.

One of them, treated at just 7 months, has appeared to stabilize instead of following the typical quick slide toward death by age 4.

"It seems right now that she's not degenerating," Flotte said. "But I would say it's too early to say that definitively."

Tay-Sachs is a fatal disorder that tends to affect babies of Eastern-European Jewish ancestry, along with other ethnicities including Cajun and Irish. They usually seem to develop normally for the first few months, but as the disease kills off their nerve cells, they lose the ability to move or breathe on their own.

Flotte says the brain MRI of the baby treated at 7 months looks encouraging, and a clinical trial in more than a dozen patients is expected to begin soon.

Edited highlights of our conversation follow.

You've just presented at a gene therapy conference. What did you report?

We reported the first two patients ever treated with gene therapy for Tay-Sachs disease two infants treated at UMass Memorial Medical Center. What we presented was that these two patients were both treated safely. The vector[the engineered virus that delivered the genetic fix] was administered directly into the brain.

We saw bio-activity, which basically means that we partially restored the enzyme that is missing in Tay-Sachs disease. And the patients were able to tolerate that safely. Also, in one of the cases, with the patient treated early in the course of the disease, we've seen some stabilization of the patient's condition.

What do you mean by stabilization?

One of the patients was treated at 2-1/2 years of age, and that patient had really advanced disease. And we've seen the biochemical effect, but really no clinical effect.

The second patient was treated between 6 and 7 months of age, and in that patient, it appears, although it's still very early, that the patient may be having some continued preservation of her ability to sit up and control her muscles. She's basically seeming to have a more gradual progression at the current time, really being stable at a time point when we might be expecting her to lose some of these developmental milestones.

The best way to explain it is that if a normal infant begins to sit up at around six months of age, Tay-Sachs babies do that, but then they tend to lose the ability to sit up some time between 10 months of age and maybe 15 months of age. The last time we assessed the patient, at 10 months of age (and she's now close to 12 months of age), she seems to not be losing any of the strength required to sit up. We have her older siblings for comparison, and it's encouraging that she seems to be progressing less than they did. We also saw some encouraging signs on her brain MRI.

It seems right now that she's not degenerating. But I would say it's too early to say that definitively. If you think about the progression of development as the slope of a line, the line is flat at this point. It's not going up or going down. The next assessment will be very important, to see whether she's continuing to be flat, which would be a major benefit, or whether she's regressing but just a little bit more slowly.

When you say flat, she's also not advancing as a typical child would?

That is right. It looks like preservation of function rather than gaining. But her oldest sibling died before his third birthday. So considering how fast these patients can decline, a preservation or stabilization could be very important.

It's important to note, too, that we are just at the very beginning. The first patient got the vector injected just into the fluid around the brain, the cerebro-spinal fluid, not into the brain tissue. The second patient got a portion of it injected into the thalamus, which projects out to the entire brain tissue. It's kind of the relay center of the brain, and it can actually ship enzyme out all over the brain.

No one's ever tried that in a humans before, so that was really an important milestone, that intra-thalamic injection. As the trials progress, a larger dose will be injected into the thalamus.

Why has there never been an injection into the thalamus in humans before? What's the challenge?

One challenge is that it is a completely irreplaceable structure. Effectively, all motor and sensory function relays through the thalamus. So if you were to have bleeding or injury to the thalamus, it could cause a stroke or a persistent pain syndrome. So it is somewhat risky. On the other hand, when you're dealing with the infantile form of Tay-Sachs, it's so tragic that it warrants a rather risky approach.

It's been done many times in animals, but this was the first time doing it in patients.

What's next? A full clinical trial?

Yes, Axovant has licensed the program. This first program was done all at UMass Medical School and UMass Memorial Medical Center, and the program is now licensed to Axovant, and they are planning in the near future to do a Phase 2 trial, which we will still be involved in.

It will entail increasing the proportion of the vector injected into the thalamus, so that we will get to the exact proportional dose that was used to correct all of the different animal models that have been treated: a mouse, a sheep and a cat model.

UMassMed Magazine has more on the school's Tay-Sachs gene therapy work here.

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Early Report: Baby Treated With Gene Therapy For Deadly Tay-Sachs Disease Appears To Stabilize - WBUR

The U.S. National Institutes of Health (NIH) wants to cure HIV and sickle cell disease with gene therapies, and will invest $100 million over the next four years towards that goal, the agency announced today (Oct. 23).

For this effort, the NIH will partner with The Bill & Melinda Gates Foundation, which will also invest $100 million.

Critically, the partnership aims to make the therapies affordable and accessible to people around the world, particularly in developing countries, where the burden of these diseases is greatest.

"This is a very bold goal, but we have decided to go big," Dr. Francis Collins, director of the NIH, said in a news conference today.

The effort aims to have the therapies ready for testing in clinical trials in the U.S. and sub-Saharan Africa within the next seven to 10 years.

Related: 10 Amazing Things Scientists Just Did with CRISPR

The majority of the 38 million people with HIV live in developing countries, with two-thirds living in Sub-Saharan Africa. For sickle cell disease, the majority of cases also occur in Sub-Saharan Africa.

The NIH has been trying to find a cure for HIV for "decades and decades," said Dr. Anthony Fauci, director of The National Institute of Allergy and Infectious Diseases. Although current treatments with antiretroviral therapy (ART) are effective at suppressing the virus in the body, they are not a cure, and must be taken everyday. What's more, there are millions of people with HIV who don't have access to ART treatment.

Although scientists are working to develop gene-based cures for HIV, these approaches are often costly and would be difficult to implement on a large scale, Fauci said. For example, some of these therapies take cells out of a patient's body and then re-infuse them, an expensive and time-consuming intervention.

For this reason, the new collaboration will focus on developing cures that use "in vivo" approaches, meaning they happen inside the body, Fauci said. One example of this could be to remove the gene for the CCR5 receptor, which HIV uses to get inside cells. Another idea is to excise the HIV "proviral" DNA that has copied itself into the human genome and lurks in the body even after years of treatment.

Similarly, for sickle cell disease, the goal would be to develop an in vivo therapy that could repair the genetic mutation that causes the disease. This would require a gene-based delivery system that could selectively target the mutation.

"Beating these diseases will take new thinking and long-term commitment. I'm very pleased to see the innovative collaboration announced today, which has a chance to help tackle two of Africa's greatest public health challenges," Matshidiso Rebecca Moeti, the World Health Organization's Regional Director for Africa, said in a statement.

Still, much work would be needed to make sure these therapies are safe and effective.

"It is very clear we have a ways to go, which is why this is a 10 year effort to try and take that promise and turn it into a reality," Collins said.

Earlier this year, the Trump Administration announced a plan to end the HIV epidemic in the U.S. in 10 years.

Originally published on Live Science.

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Can Gene Therapy Cure HIV? US Gov't. Is Banking $100 Million On It. - Livescience.com

The National Institutes of Health (NIH) announced a partnership with the Bill and Melinda Gates Foundation on Wednesday to fund the development of targeted cures for HIV and sickle cell disease with a view to helping people in developing countries using gene therapy. With most of the populations affected by each disease residing in sub-Saharan Africa, treatments are being sought with regional conditions in mind.

The NIH and the Gates Foundation are investing $100 million in the initiative to develop low-cost gene therapies. The announcement follows President Donald Trump's pledge in his 2019 State of the Union address that the United States would eradicate HIV within the next decade. The Trump administration has also tried to draw more attention to sickle cell disease (SCD) in the past few years, according to a press release from NIH.

Sickle cell disease is a blood disorder that can cause anything from mild pain to heart failure. Human immunodeficiency virus (HIV) is a communicable disease that, if left untreated, wipes out the immune system. People with SCD inherit the disease from their parents, whereas HIV is acquired through blood contamination with certain bodily fluids of an infected person. While the mechanisms of transmission are different, both diseases are carried in the genome of infected individuals. Globally, both diseases also disproportionately impact individuals in lower-income communitiesand scientists believe that both could be combatted with gene-based treatments.

The past few years have seen unprecedented strides toward cures for these two diseases using gene therapy, which the NIH defines as experimental technique wherein doctors insert genes into a patient's cells so their body can more effectively resist a disease. It can include inserting a healthy variant of a gene to replace the unhealthy copy that causes a disease, or placing an entirely new gene in the body to fight the disease.

"Dramatic advances in genetics over the last decade have made effective gene-based treatments a reality... Yet these breakthroughs are largely inaccessible to most of the world by virtue of the complexity and cost of treatment requirements, which currently limit their administration to hospitals in wealthy countries," the press release states. The new initiative will focus on developing treatments that can be delivered in "low-resource settings."

Speaking on the initiative's viability, Dr. Ronald Mitsuyasu, a professor of medicine in hematology-oncology at the University of California, Los Angeles with more than 25 years of experience in HIV clinical trials research, told Newsweek that this sort of solution has been attempted in the past, but gene therapy hasn't yet proved successful in treating HIV.

"There have been several attempts to use gene therapy for HIV by either incorporating genes that suppress HIV genes, producing decoys for various viruses required processes needed for viral replication, or substituting inactive genes for functional genes of HIV," he said.

But those living in developing countries have not had as many chances to benefit from these solutions as those living in places like the U.S., according to the press release.

"SCD and HIV are major burdens on health in low-resource communities around the world," the press release read. "Approximately 95% of the 38 million people living with HIV globally are in the developing world, with 67% in sub-Saharan Africa, half of whom are living untreated. Fifteen million babies will be born with SCD globally over the next 30 years, with about 75% of those births occurring in sub-Saharan Africa."

Further, the prediction indicates that three-quarters of those infants will be born into low-income countries and communities. Between 50 and 90 percent of babies born with the disease in sub-Saharan African countries will die before the age of five, according to the release.

So, the NIH and the Gates Foundation's initiative aims to identify potential cures for both diseases as well as partner with groups in Africa to identify candidates on whom these new cures can be tested.

We are losing too much of Africa's future to sickle cell disease and HIV. Beating these diseases will take new thinking and long-term commitment. I'm very pleased to see the innovative collaboration announced today, which has a chance to help tackle two of Africa's greatest public health challenges." Matshidiso Rebecca Moeti, M.B.B.S., the World Health Organization's regional director for Africa said of the initiative.

Mitsuyasu said he agreed that continued investigation into gene-based cures would eventually yield worthwhile results. "I personally believe that it should be possible to ultimately develop a gene therapy approach to overcome ... HIV," Mitsuyasu said. "Continued scientific developments in the field of gene therapy will eventually allow for the conquest of most genetic and viral gene integrated diseases."

See more here:
Gates Foundation, NIH Bet on Gene Therapy To Bring Cheap HIV and Sickle Cell Cures to Sub-Saharan Africa - Newsweek

Gene therapy is a promising therapeutic procedure for genetic disorders or diseases in which defective genes are corrected, replaced, or inactivated.

In the case of adrenoleukodystrophy (ALD) a genetic disorder caused by mutations in the ABCD1 gene that damages the myelin sheath around nerve cells gene therapy may benefit patients prior to the onset, or during the early stages, of the disease by stopping the progression of demyelination. However, the therapy cannot be beneficial after the disease has worsened significantly.

Gene therapy works by introducing the correct gene sequence into cells. Since genetic material cannot enter the cell on its own, the correct gene sequence needs to be delivered using a vector. This vector can be a modified virus that has been engineered to remove its pathogenic genetic material so that it cannot cause disease, but is still able to transfer the correct gene sequence to the host cell.

The vector can be directly injected into the patients body or into host cells grown in the laboratory and then transplanted back into the patient. Upon successful viral transfer, the host cell should be able to produce the functional protein.

In ALD, the clinician first takes out the patients own stem cells (autologous) and then inserts the correctABCD1 gene sequence into these cells using a viral vector in the laboratory. The corrected stem cells that are able to produce the functional ALD protein are then implanted back into the patients body so they may develop into nerve cells in the brain. Since the patients own cells are being used, there are fewer risks than when donor stem cells are used.

Lenti-D,an investigational gene therapy developed by Bluebird Biois currently being studied in a Phase 2/3 clinical trial (NCT01896102) in the U.S., the U.K., and France. The study aims to evaluate the safety and effectiveness of Lenti-D in boys, up to 17 years old who havecerebral adrenoleukodystrophy (CALD). Based on the preliminary data from this study,the U.S. Food and Drug Administration (FDA)designated Lenti-D a breakthrough therapy for the treatment of CALD in May 2018.

A Phase 1/2 clinical trial (NCT02559830) is recruiting patients with ALD at the Shenzhen Second Peoples Hospital in Guangdong, China. The study aims to assess the safety and effectiveness of transplanting patient-derived bone marrow stem cells, which have been genetically-corrected using a lentiviral vector, for the treatment of ALD.

Another Phase 1/2 clinical trial (NCT03727555) at the Shenzhen Geno-Immune Medical Institute also in Guangdong, China is recruiting 10 patients with ALD. The study aims to evaluate the safety and effectiveness of a lentiviral vector carrying the healthy ABCD1 gene (TYF-ABCD1) injected directly into the patients brain for the treatment of ALD.

***

Adrenoleukodystrophy News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.

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zge has a MSc. in Molecular Genetics from the University of Leicester and a PhD in Developmental Biology from Queen Mary University of London. She worked as a Post-doctoral Research Associate at the University of Leicester for six years in the field of Behavioural Neurology before moving into science communication. She worked as the Research Communication Officer at a London based charity for almost two years.

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Gene Therapy - Adrenoleukodystrophy News

Sigmund Freud never uttered the word neuroscience. Neither did Santiago Ramn y Cajal. It was biophysicist Francis Schmitt who grafted neuro with science in 1962 when he established the Neurosciences Research Program at MIT. The new moniker was intended to encompass a merging of relevant neuro disciplines, ranging as far afield as physiology, psychology, immunology, physics and chemistry.

Brains and behaviors have been scrutinized for millennia. But as psychology blogger Vaughn Bell has pointed out, the 1960s marked a shift in perspective. Neuroscience was the formal name given by Schmitt. But the period represented the beginnings of a neuroculture, that put brain science on a pedestal even leading to the familiar meme proclaiming my brain made me do it. One example was rooted in pharmaceutical companies development of psychiatric drugs that resulted in their investing millions both into divining the neurochemistry of experience and into massive marketing campaigns that linked brain functions to the psyche, Bell notes.

The field received an adrenaline boost precisely 50 years ago with the founding of the Society for Neuroscience, allowing Schmitts collaborative vision to be globally shared. SFNs first annual meeting in 1971 drew 1,395 attendees to Washington, D.C. This years wrapped up on October 23, bringing more than 27,500 to Chicagoand the annual numbers have occasionally topped 30,000. SFN now boasts 37,000 members from more than 95 countries.

Anything to do with the topic brain found a place among the more than 14,500 abstracts of unpublished work presented in 2019 on themes ranging from the mechanisms of sleep to cocaine craving. But the society has had to adapt its U.S.-based get-together this year to respond to a world of closing national borders.

Some members were unable to get visas to enter the U.S., in part because of the U.S. travel ban, which includes broad restrictions on visits from Iran,Libya,Syria,Yemen,Somalia,North KoreaandVenezuela. In response, SFN initiated a program called Science Knows No Borders in which would-be attendees had a PDF printed out and posted or else PowerPoints and a recorded talk proferred in their absence. An Iranian doctoral student, Shahrzad Ghazisaedi, from University of Toronto, a neuropathic pain researcher, was one among about a dozen people who took advantage of the program (not all of them necessarily subject to the travel ban). Her poster entitled Sex specific DNA methylation pattern in spinal cord and periaqueductal gray (PAG) before and after peripheral injury could be seen Monday afternoon by attendees during a session entitled Central Nervous System Mechanisms in Pain.

For those who actually were able to make it, a range of topics caught the eye: research on nervous system immune cells implicated in a range of disorders, a gene therapy for converting the brains support cells to neurons for treating Alzheimers, a prosthetic forearm that provides a sense of touch and synchronization of brain waves between two people holding hands. Also, a group of scientists got together to start planning a test in humans to determine which of two theories of consciousness is more likely to be correct.

Another theme that stood out was the challenge of working with miniaturized brain facsimiles, called organoids, that show promise of more faithfully replicating what goes on in the human organ than a mouse brain can. Organoids, though, are too close to a Mary Shelley creation for some people. At the conference, members of the Green Neuroscience Laboratory in San Diego called for a research moratorium on organoid tissue implanted into mice or other animals, a technique already in use. In an abstract for their talk, they ventured that the technology is perilously close to crossing an ethical Rubicon in which organoids may experience sentient activity and behavior. The group advocates that methods should be developed to ascertain whether any given organoid has the ability to sense and react to its surroundings.

At a press conference of scientists who grow the five-millimeter-diameter mini brains, ethical debate was welcomed, but the researchers also tried to place their work in context. Paola Arlotta from Harvard showed a video of organoids, at most the size of small peasnothing resembled an imagined brain-in-a-dish. The brain bits are also difficult to work withchallenging to grow reproducibly and their cells do not mature to become an exact replica of human cells, but instead end up with a confused identity. Researchers think the kinks can be worked out, but, even then, that may not pave the way for growing full-sized organs.

Most scientists are not interested in figuring out how to grow a human brain in a dish, says Arnold Kriegstein, of the University of California, San Francisco. They are more interested in a particular disease mechanism or a certain process they want to study. And that really requires a reductionist system. It's too complicated to study an intact human brain. What you really want are the important elements, which you can dissect and delve into in great detail in the laboratory.

Everyone agreed that discussion about mini-brain ethics is warranted. But as far as existential threats, tiny tissue nuggets run amok may not be at the top of a list that includes antibiotic resistance, climate change and self-driving cars engineered with internals that produce a loss of control that resembles a wayward 737 MAX.

Read the original here:
Society for Neuroscience at 50 Delves into Mini Brains, Gene Therapy, Prosthetics and All Else Related to Our Three-Pound Wonder - Scientific American

Dive Brief:

The EMA's green light for Bluebird's manufacturing removes a final hurdle standing in the way of marketing the gene therapy, which costs $1.8 million per patient.

A requirement from European authorities to narrow drug product specifications for Zynteglo forced the company to delay the gene therapy's launch later than when Wall Street analysts had expected.

In a statement, Apceth said it's ready for the challenge to bring Bluebird's treatment to market. Between 2,000 and 3,000 patients in the European Union would be eligible under the conditions approved by regulators for Zynteglo's use.

Bluebird has cautioned investors to take a long view of the new treatment's prospects, and to expect a slow start. In addition to winning approval for the new manufacturing specifications, Bluebird has to navigate through healthcare systems that aren't used to paying large sums for a one-time treatment.

In hopes to alleviating those problems, the company has offered an installment plan that would require later payments only if the treatment continues to benefit patients. The hope is that Zynteglo saves healthcare dollars by sparing beta-thalassemia patients the need for regular blood transfusions and the complications that can go along with them.

Patients with the blood disorder carry a genetic mutation that hinders the body from effectively producing the crucial oxygen-carrying protein hemoglobin. As a result, they often require transfusions every two to five weeks to fight anemia.

"This is one step along the commercial journey as we advance our ongoing launch and market access activities on a country-by-country basis," said Alison Finger, Bluebird's chief commercial officer, in the company's statement on the EMA's nod.

In a September company presentation, Bluebird said it wants to make sure to "get the model right" as it looks toward future gene therapies it's developing in its pipeline. The company is initially planning to offer Zynteglo through treatment centers in Germany, Italy, the U.K. and France, with a drug manufacturing facility in Munich.

Read more:
Bluebird gets European green light for gene therapy production - BioPharma Dive

A gene therapy for a rare blood disorder has shown what the manufacturer calls the first evidence of long-term improvement associated with the disease.

New York-based Rocket Pharmaceuticals said Thursday that it had presented long-term follow-up data from the Phase I/II study of RP-L102, its gene therapy for Fanconi anemia, at the annual congress of the European Society of Cell and Gene Therapy in Barcelona, Spain. The company said it represented the first evidence of long-term improvement and stabilization in blood counts and durable mosaicism among patients who received the therapy without the use of the conditioning regimens normally used for allogeneic stem cell transplants, which the company calls Process A.

Shares of Rocket were up slightly on the Nasdaq following the news. RP-L102 is a lentiviral vector-based gene therapy. Most other gene therapies in development, and both of the currently marketed ones Spark Therapeutics Luxturna (voretigene neparvovec-rzyl) and Novartis Zolgensma (onasemnogene abeparvovec-xioi) are adeno-associated viral vector-based.

According to the data, representing four of nine patients, there were improved blood counts and long-term bone marrow mitomycin C (MMC) resistance, thereby indicating durable phenotypic correction. The data met or exceeded a 10 percent threshold that the company said the Food and Drug Administration and European Medicines Agency had agreed to for its upcoming Phase II registration study, for which it plans to start enrolling patients by the end of the year.

FA is a rare, genetic bone marrow failure disorder, half of whose patients are diagnosed before the age of 10, while about 10 percent of patients are diagnosed as adults, according to the National Organization for Rare Disorders. It is often associated with progressive deficiency of production of red and white blood cells and platelets in the bone marrow and can eventually lead to certain solid and liquid tumor cancers. It occurs in 1-in-136,000 births and is more common among Ashkenazi Jews, Spanish Roma and black South Africans.

These results indicate the feasibility of engraftment in FA patients using autologous, gene corrected [hematopoietic stem cells] in the absence of any conditioning regimen, said Dr. Juan Bueren, scientific director of the FA gene therapy program at Spains Center for Energy, Environmental and Technological Research, in a statement. This indicates the potential of this therapeutic approach as a definitive hematologic treatment, while avoiding the burdensome side effects associated with allogeneic transplant, including the risk of post-transplant mortality and a substantially higher risk of head and neck cancer.

Photo: virusowy, Getty Images

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Rocket's gene therapy shows long-term efficacy in rare blood disorder - MedCity News

In Junedata on three subjects in a phase II trial of Krystal Biotechsepidermolysis bullosa gene therapy sent the group's share price up 41%. Today a final update from the trial, including results from two new patients, left investors unmoved.

This might have something to do with the updated data showing that two lesions that had been successfully treated with Krystals therapy at 90 days had reopened a month later, raising questions about whether the treatment works in the long term.

The two new patients with severe recessive dystrophic epidermolysis bullosa (RDEB) had beenadded to the trial in June 2019, after the initial data release(Krystal plays down dropout to claim a mid-stage win, June 25, 2019). Bercolagene telserpavec or B-Vec for short, formerly called KB103, was administered to one wound on each patient every other day for two weeks, or until the wound closed completely. The other wound was treated with a placebo gel.

This differs slightly from the earlier phase II patients, who had B-Vec administered to two wounds each and placebo to a third.In its press release Krystal trumpeted that, of all 10 wounds treated in the phase I and phase II trials, nine had healed at 90 days.

The unhealed 90-day lesion was a chronic wound, reported to have been open for over four years, in one of the patients in the first phase II cohort. It was still only 42% closed at 90 days following the initial administration of B-Vec. The wound was re-dosed with B-Vec approximately three and a half months later, and healed within a week of this second dose.

Reopening

But the company glossed over the fact that, at four months, two of the healed B-Vec-treated wounds in cohort 1 had reopened: at 120 daysa lesion on one patients back had returned to only 77% closure, and another patient had a lesion on their left upper arm return to 85% closure.

Moreover, one of the placebo-treated wounds that had not healed at 90 days did heal at 120. At the four-month point, across both phase II cohorts, the success rates are 63% for B-Vec versus 20% for placebo not quite emphatic as the earlier 90% versus 14%.

One question iswhich time point is the more important? On clinicaltrials.gov the primary endpoint cutoff is listed as wound healing at 24 weeks a completely different point, and one that has not yet been reached, despite Krystals statement that this would be the final update from the phase II trial.

EB is a cyclical disease. Wounds open, close and reopen in the natural course of the condition even without treatment, so it can be tricky to show a drugs effect. Krystal intends to move B-Vec into phase III, and investors might want to take careful note of the time point regulators pick for the primary endpoint.

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Gene therapys duration is less than Krystal clear - Vantage

Cobra Moradian, Fatemeh Rahbarizadeh

Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Correspondence: Fatemeh RahbarizadehDepartment of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Jalal AleAhmad Highway, Tehran 14115-111, IranTel +98 21 82883884Fax +98 21 82884555Email rahbarif@modares.ac.ir

Background: Breast cancer stem cells (BCSCs) are cells with a higher ability to metastasis and resistance to conventional treatments. They have a phenotype of (CD44high/CD24low) and the unlimited ability for proliferation. Development of strategies to target the BCSC population may lead to the establishment of more effective cancer therapies. Pseudomonas exotoxin A (PE) is a potent cytotoxic protein. CXCR1 promoter provides BCSC and HER2 specificity on transcription level. 5UTR of the basic fibroblast growth factor-2 (bFGF 5UTR) provides tumor specificity on translation level. Here, we utilized a mutant form of PE encoding DNA PE38, CXCR1 promoter and bFGF 5UTR to target BCSCs.Methods: The stemness of SK-BR-3, MDA-MB-231 and MCF10A cell lines were evaluated based on the expression of the CD44high/CD24low stem cell signature and the ability to form mammospheres. Then, the cell lines were transfected with constructs encoding luciferase/PE38 under the control of the CMV/CXCR1 promoter with or without bFGF 5UTR. Luciferase protein expression was evaluated using dual-luciferase reporter assay. PE38 transcript expression was measured by real-time PCR, and the cytotoxic effect of PE38 protein expression was determined by MTT assay.Results: The percentage of CD44high/CD24low population did not correlate to mammosphere forming efficiency (MFE). Given that the percentage of CD44 high/CD24 low is not a conclusive BCSC profile, we based our work on the mammosphere assay. However, in comparison with MCF10A, the two tumorigenic cell lines had higher MFE, probably due to their higher BCSC content. Reporter assay and real-time PCR results demonstrated that CXCR1 promoter combined with bFGF 5UTR increased BCSC-specific gene expression. Meanwhile, tightly regulated expression of PE38 using these two gene regulatory elements resulted in high levels of cell death in the two tumorigenic cell lines while having little toxicity toward normal MCF10A.Conclusion: Our data show that PE38, CXCR1 promoter and bFGF 5UTR in combination can be considered as a promising tool for killer gene therapy of breast cancer.

Keywords: breast cancer stem cell, PE38, CXCR1 promoter, bFGF-2, HER2, mammosphere

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Targeted Toxin Gene Therapy Of Breast Cancer Stem Cells Using CXCR1 Pr | OTT - Dove Medical Press

During the third-quarter financial call, Vasant Narasimhan, CEO of Novartis, noted that questions from European and Japanese regulators regarding chemistry, manufacturing and controls (CMC) were behind expected decision dates on Zolgensma (onasemnogene abeparvovec) being pushed back into 2020.

At present, the company expects to receive opinions from the European Medicines Agency (EMA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) in the first quarter and the first half of 2020, respectively.

Narasimhan revealed few other details regarding the questions, only that there were an extensive set of questions with respect to manufacturing, to which it had submitted responses. Reuters stated that he also confirmed that the decision delay was not due to the revelation of data manipulation in August.

Despite the setback on potential approval date, the company was able to confirm that the product had achieved US sales of $160m (143m), arriving higher than analyst predictions of $98m (88m).

When questioned on the patient numbers this related to, on paid programs, Narasimhan confirmed that approximately 100 patients had been treated though other patients had received the gene therapy through treatment in clinical trials.

Once approved in elsewhere in the world, Narasimhan predicted such number could increase rapidly: I think in some countries in Europe, as well in the Middle East, there could be very strong demand coming very quickly after approval.

He cited pent-up demand as a reason that sales would increase quickly, and also pointed to early access programs being made available in France, Portugal and Germany as another positive long-term sign for the product.

The company will need to see substantial return on the product, after investing $8.7bn in the AveXis acquisition to gain access to the technology.

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Novartis gene therapy held up by manufacturing questions - BioPharma-Reporter.com

PTC Therapeutics has presented new long-term outcome data from its investigational gene therapy, PTC-AADC, in patients living with aromatic L-amino acid decarboxylase (AADC) deficiency.

The one-time gene therapy was found to give patients the ability to sit, walk, and talk, from data representative of up to five years of follow up post-treatment.

The new analysis evaluated outcomes of 26 patients with AADC deficiency across three separate clinical trials, and found that 12 months post-treatment with PTC-AADC, patients mean body weight had increased from 12.0 kg to 15.2 kg, and the frequency of oculogyric crises (involuntary upward eye movement) was reduced.

The data, presented at the Child Neurology Society 48th Annual Meeting, is a result of the most comprehensive analysis of patients treated with PTC-AADC to date.

Unfortunately, there are currently no approved therapies that address the underlying cause, and as such patients with severe AADC deficiency have a high risk of death during childhood.

The company is excited to see the transformational effects in AADC deficiency patients in this long-term study as patients with severe AADC deficiency never achieve the ability to sit, walk or talk, said Stuart Peltz, chief executive officer of PTC Therapeutics.

He also announced that PTC is on track to submit a biologics license application (BLA) to the FDA by the end of the year and are proud to be on the verge of bringing the first commercial treatment for AADC deficiency patients, which is in line with our mission of bringing clinically differentiated treatments to patients with rare disorders.

AADC deficiency is a rare genetic condition caused by a mutation in the dopa decarboxylase (DDC) gene, resulting in a lack of functioning AADC enzyme, which is responsible for the final step in the synthesis of key neurotransmitters dopamine and serotonin.

It results in delays or failure to reach developmental milestones such as head control, sitting, standing, walking, or talking, low muscle tone, severe, seizure-like episodes involving involuntary eye movement, autonomic abnormalities, and the need for life-long care.

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Investigational gene therapy shows long-term success in AADC - PharmaTimes