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takyon writes:

A U.S. Food and Drug Administration advisory panel has recommended against the approval of Sarepta's eteplirsen, a drug intended to treat Duchenne muscular dystrophy (DMD). Two other experimental DMD drugs have already been rejected. The recommendation came despite the emotional testimony of children who had apparently seen improvements due to the experimental treatment. Representative Mike Fitzpatrick, R-Pa. also spoke on behalf of a constituent with DMD. However, concerns were raised about the small sample size of the trial:

"I am very sorry to say that approval of eteplirsen based on today's data would set a dangerously low bar for all drugs in the future," said Gottschalk, a senior fellow at the National Center for Health Research, a nonprofit in Washington, D.C. "Treatments for rare diseases can be proven on small samples, but not based on 12 patients in a poorly designed study with ambiguous results. These boys and their families deserve better."

The problem, FDA scientists said earlier in the day, is that, due to its small size and design, the study Sarepta submitted to the agency cannot prove that eteplirsen deserves credit for the boys' ability to remain on their feet. Although the company says dozens more boys are now taking the drug, its case with the FDA rests on only the study involving the 12 boys in the orange t-shirts. Except for the first 24 weeks, all of the boys in that study have been taking the drug. With no long-term placebo group, Sarepta chose to compare them to untreated boys from a registry of DMD patients. These types of studies tend to have more favorable results than studies that randomly assign participants to the active treatment or a placebo, Dr. Robert Temple, deputy director of the FDA office that evaluates nervous system drugs, told the advisory committee.

The advisory panel's 7-3 recommendation (with three abstentions) is not the final word on eteplirsen, but the FDA generally follows such recommendations. Sarepta's shares plummeted on the news.

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An Anonymous Coward writes:

Dr. Derek Lowe, from In the Pipeline, writes:

So since drug pricing and FDA regulations are so much in the news, it would seem like the perfect time for a small company to game the system for big profits, right? That's apparently what Marathon Pharmaceuticals believes. They just got approval for deflazacort, a steroid, as a treatment for Duchenne Muscular Dystrophy.

[...] So what's not to like? Well, this drug has been around since the early 1990s. Marathon most certainly did not invent it. Nor did they think of applying it to DMD patients – the biggest clinical trial of the drug for that indication was done over twenty years ago, by someone else. DMD patients in the US were already taking the (unapproved) drug by importing it from Canada. Marathon just dug through the data again and ran a trial in 29 patients themselves, from what I can see. I should note that this is not any sort of cure, nor does it address the underlying pathology of the disease. The steroid treatment makes muscle strength in DMD patients stronger – barely. But even for that benefit, US patients will now have to get it from Marathon at something like 50 to 100 times the former price.

[...] So while I defend the FDA's function of making it tough on new drugs (making them prove safety and efficacy), I cannot stand how loose they are with old generic compounds. The agency hands out extremely valuable rewards like lollipops in these cases – a priority review voucher can be sold for hundreds of millions of dollars

[...] And they're also allowing the likes of Marathon to make the rest of the drug industry look like greedy sociopaths. Marathon, Catalyst, T*ring and all the rest of the people who are pulling these tricks have the word "Pharmaceuticals" in their name, but they are not drug companies. They discover nothing. They do no research. They take virtually no risks. They exist only to play legal games and watch the money roll in.

[...] As for the FDA, the agency probably can't change this on its own, though, even if it wants to – Congress has to act to give them the authority to deny market exclusivity or priority review vouchers under some conditions. Either that, or we should rethink these incentives entirely, because they are (clearly) too easy to exploit for fast bucks.

https://en.wikipedia.org/wiki/Deflazacort

Also at ArsTechnica.

Original Submission

An Anonymous Coward writes:

Dr. Lowe, from In the Pipeline, writes an update on a story we covered earlier this year:

http://blogs.sciencemag.org/pipeline/archives/2017/04/25/marathon-pharmaceuticals-cashes-out

https://en.wikipedia.org/wiki/Deflazacort

The priority review voucher is an incentive program that provides companies, that get a drug approval for a neglected or rare disease, a voucher that entitles them to a more speedy review (under six months instead of ~10 months) for a future drug. This is a great program; however, Marathon Pharmaceuticals deliberately exploited this program by conducting a very small trial using a generic drug (another loophole).

Previous Story: https://soylentnews.org/article.pl?sid=17/02/11/2116252

Original Submission

An Anonymous Coward writes:

Brain involvement in Duchenne muscular dystrophy was described by Duchenne de Boulogne himself in 1886. It has been largely ignored.

Duchenne muscular dystrophy (DMD) is a fatal genetic disorder that predominantly affects male children. There is no cure. Besides severe muscle wasting, the disease also affects the brain.

DMD is caused by DNA mutations that result in the body-wide loss of a protein called dystrophin. Dystrophin is essential for muscle strength and function. It acts like a shock absorber, without it muscles become weak and break down. Most affected children will be in wheelchairs by their early teens with death typically occurring in early adulthood because of complications with the heart or lungs.

Duchenne is first and foremost a muscle disorder, but the intelligence of individuals with the disease is lower than the general population. Intellectual disability, epilepsy, autism and attention deficit hyperactivity disorder are also common. Mounting evidence links these symptoms to the loss of dystrophin in the brain. But given the more urgent need to treat the muscles, brain involvement in DMD has been ignored.

So what does dystrophin do in the brain and why is its loss linked to cognitive and behavioural problems? We understand very little. Unlike muscle, the brain produces several different types, or isoforms, of dystrophin. These are found in different regions of the brain, and in different parts of the cell. Proposed functions are therefore diverse and range from a scaffolding function in the nucleus to roles in synapse activity.

[...] The lack of understanding of how dystrophin functions in the brain is a major roadblock to the development of effective whole-body treatments. There is an urgent need for fundamental research in this area. My postgraduate research student, Amanda Ash, and I have this month launched a crowdfunding campaign to raise awareness and funds to help kick start such work. The platform, Experiment, recently surpassed £1,000,000 in total funding raised. Scientists using the platform have been featured in The Economist, Forbes, Nature, and The New York Times.

https://thebiochemistblog.com/2017/09/07/what-is-a-muscle-protein-doing-in-the-brain/

Original Submission

takyon writes:

Gene editing of dogs offers hope for treating human muscular dystrophy

Fighting fire with fire, researchers working with dogs have fixed a genetic glitch that causes Duchenne muscular dystrophy (DMD) by further damaging the DNA. The unusual approach, using the genome editor CRISPR, allowed a mutated gene to again make a key muscle protein. The feat—achieved for the first time in a large animal—raises hopes that such genetic surgery could one day prevent or treat this crippling and deadly disease in people. An estimated 300,000 boys around the world are currently affected by DMD.

The study monitored just four dogs for less than 2 months; more animal experiments must be done to show safety and efficacy before human trials can begin. Even so, "I can't help but feel tremendously excited," says Jennifer Doudna of the University of California, Berkeley, who heard the results last week at a CRISPR meeting she helped organize. "This is really an indication of where the field is heading, to deliver gene-edited molecules to the tissues that need them and have a therapeutic benefit. Obviously, we're not there yet, but that's the dream."

[...] The study offers little evidence that dogs regained muscle function, however, and that, coupled with the short duration of the study and the small number of animals studied, left some scientists less enthusiastic. One researcher in the tight-knit DMD field who asked not to be named wonders whether the study was rushed to help draw investment in Exonics Therapeutics, a Boston-based company Olson launched last year to develop the potential treatment.

[...] Another challenge was to alter billions of muscle cells throughout a living animal. So the team enlisted a helper: a harmless adeno-associated virus that preferentially infects skeletal muscle and heart tissue. Two 1-month-old dogs received intramuscular injections of the virus, engineered to carry CRISPR's molecular components. Six weeks later, those muscles were making dystrophin again. Those results led the researchers to give an intravenous infusion to two more dogs, also 1 month old, to see whether the CRISPR-carrying viruses could add the genome editor to muscles throughout the body. By 8 weeks, Olson told the meeting, dystrophin levels climbed to relatively high levels in several muscles, reaching 58% of normal in the diaphragm and 92% in the heart. But because the dogs were euthanized, Olson could show little evidence that they had avoided DMD symptoms, save for a dramatic video of a treated dog walking and jumping normally.

Also at Science News.

Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy (DOI: 10.1126/science.aau1549) (DX)

More about Duchenne muscular dystrophy at Wikipedia.

Related: Scientists Create Extra-Muscular Beagles
FDA Panel Recommends Rejection of Duchenne Muscular Dystrophy Treatment
Nonviral CRISPR-Gold Editing Technique Fixes Duchenne Muscular Dystrophy Mutation in Mice
CRISPR Used to Epigenetically Treat Diseases in Mice

Original Submission

takyon writes:

Mammoth Biosciences adds the final piece of the CRISPR diagnostics puzzle to its toolkit

With the announcement today that Mammoth Biosciences has received the exclusive license from the University of California, Berkeley to the new CRISPR protein Cas14, the company now has the last piece of its diagnostics toolkit in place.

Cas14 is a newly discovered protein from the lab of Jennifer Doudna, a pioneer in gene-editing research and a member of the first research team to identify and unlock the power of CRISPR technology. Doudna and Mammoth Biosciences co-founder Lucas Harrington were part of the team of researchers to identify the new Cas14 protein, which can identify single-stranded DNA. The journal Science published their findings [DOI: 10.1126/science.aav4294] [DX] in October 2018.

"With the addition of this protein that is DNA binding and target single strands, it really means we can target any nucleic acid," says Mammoth chief executive Trevor Martin. "It's an extension of the toolbox." The licensing deal moves Mammoth one step closer toward its goal of low-cost, in-home molecular diagnostics for any illness. "The idea is we want to make this test so affordable that you can imagine going down to your CVS or Walgreens so you can bring this access to molecular level information [to questions like] if my kid has strep or flu before dropping them off to school."

See also: CRISPR-Cas14: a family of small DNA-targeting enzymes enabling high-fidelity SNP genotyping

Related (all involving Dr. Jennifer Doudna): The Rapid Rise of CRISPR
Compact CRISPR Systems Found in Some of World's Smallest Microbes
Nonviral CRISPR-Gold Editing Technique Fixes Duchenne Muscular Dystrophy Mutation in Mice
CRISPR Used to Cure Duchenne Muscular Dystrophy in Dogs... by Further Damaging DNA
CasX Protein Works for Gene Editing in Bacterial and Human Cells

Original Submission