News

Novartis will resume clinical development of branaplam to treat spinal muscular atrophy after a two-year pause brought on by safety concerns, the Swiss company announced in a letter published by Cure SMA. The ongoing clinical trial will start enrolling patients as soon as the research team obtains approvals by health authorities and the ethics committee. The study recruits infants younger than six months with type 1 SMA. All will receive branaplam, the name Novartis chose for its compound when reopening clinical investigations. While the study originally only included four European study centers — in Belgium, Germany, Denmark and Italy — Novartis said it plans to add more sites including some in the United States, following a green light from the U.S. Food and Drug Administration (FDA). The branaplam clinical trial halted new enrollments in May 2016 after simultaneous animal studies linked branaplam to unexpected nerve damage and other injuries. Infants already enrolled continued treatment and have been closely monitored. Novartis has worked with outside experts to understand the meaning of the animal findings. The fact that enrollment has resumed signals that Novartis — which has not commented on its relevance — no longer perceives the animal data as an immediate patient hazard. Besides resuming recruitment, the company has modified its trial design after considering feedback from the babies’ parents and study investigators. For instance, infants can now receive their weekly dose of branaplam orally, instead of via a feeding tube, which was the only option when the trial started. The company also added nerve tests to the trial as an additional safety procedure. As clinical development of branaplam continues, Novartis is also working with regulators to expand drug testing to include patients with other types of SMA.

Biotech company Scholar Rock has Secured a key U.S. Patent for a Potential SMA Therapy that targets Myostatin The U.S. Patent and Trademark Office has issued a patent for antibodies that selectively bind and inhibit myostatin – a protein that naturally prevents muscle mass growth. This new patent granted to Scholar Rock will protect its drug candidate, SRK-015, which the Cambridge, Massachusetts company is developing to improve muscle strength and motor function in patients with spinal muscular atrophy and other motor disorders. Previous studies have showed that people with mutated myostatin genes also have significantly larger muscle mass. This suggests that inhibiting myostatin's activity could potentially treat several motor illnesses, including SMA. Preclinical testing in non-human primates has shown SRK-015’s potential to improve muscle cell function and strength. Animals given SRK-015 improved lean muscle mass as well as the function of some specific muscle fibers that are often simpaired in many SMA patients. Scholar Rock is working to take its lead candidate for treatment of SMA into clinical trials. The company plans to evaluate SRK-015's safety and effectiveness in combination with other therapies designed to correct the genetic defects that lead to SMA. By mid-2018, Scholar Rock also intends to address SRK-015's potential as a standalone therapy in patients with certain subtypes of the rare genetic disorder. The recently issued patent will provide broad protection for SRK-015 and other therapeutic antibodies that use the same mechanism of action. These antibodies can be explored as therapeutic strategies for several neuromuscular and other diseases.

This year's Boston Rare Disease Film Festival will Feature an SMA Documentary Gareth Burghes' documentary, Life & Atrophy, which runs 24 minutes, will be part of Disorder: The Rare Disease Film Festival — a first-of-its-kind event in Boston this early October. The festival covers more than two dozen rare diseases. The 30 films, which will be shown in seven screenings, range in length from one to 65 minutes. Life & Atrophy is billed as “a documentary following one family’s story to defy genetic fate.” Burghes said the idea for his movie stemmed from his geneticist father's involvement in  clinical trials of SMA patients. It tells the story of Miles McIntosh, a 5-year-old boy with SMA type 2, as his parents, Nikki and Tony McIntosh, sign him up for a trial to test the recently FDA-approved therapy Spinraza. Burghes said that SMA “has gone from an orphan disease with nearly nothing known about it, to now having its first FDA-approved drug on the market, as well as other treatments in the pipeline. The film represents what can be accomplished when families, researchers, and pharmaceutical companies join together to solve complex diseases.” The Boston film festival is the brainchild of two fathers --Daniel DeFabio, whose son has Menkes disease, a rare disorder that affects only one in 100,000 newborns -- and Bo Bigelow, who's daughter Tess has a genetic disease that’s even more rare. Only 23 people worldwide have it; there isn’t even a name to describe her illness. The Rare Disease Film Festival runs Oct. 2-3 in Boston. The SMA documentary Life & Atrophy will air at 2:30 p.m. on Oct. 2nd .

Cure SMA will host a webinar on spinal muscular atrophy (SMA) today at 1 p.m. EST. The event focuses on access to Spinraza — the only U.S. government-approved therapy to treat the disease, CureSMA said in a press release. Topics to be covered include the current status of dosing in individual…

Ionis Pharmaceuticals has received $40 million in milestone earnings from Biogen following Japanese regulatory approval of the price of  Spinraza, Biogen's treatment for spinal muscular atrophy. So far, Ionis has earned more than $435 million from Biogen in Spinraza-related regulatory approvals and sales royalties, it said in a press release. The market performance speaks to the overwhelming success that the drug is having in treating the SMA patient population. Spinraza has been approved by U.S, European, Canadian, Brazilian and now Japanese regulatory agencies. Ionis is now working to bring the treatment to other countries including Switzerland, Israel, South Korea and Australia, where it is now under review by regulatory agencies Biogen licensed global development, manufacturing and commercialization rights to Spinraza from Ionis in August 2016. In so doing, it assumed responsibility for all activities and costs associated with the drug. Ionis is eligible to receive tiered royalties on Spinraza sales up to a percentage in the mid-teens, in addition to up to $150 million in milestone payments based on regulatory approvals. Spinraza became the first approved SMA treatment in December 2016, when the U.S. Food and Drug Administration supported its use in children and adults. The FDA made that decision within three months of Biogen's regulatory filing. Biogen sponsors one of the largest Expanded Access Programs worldwide, offering Spinraza free of charge to patients requesting it in countries that have not yet approved its use. About 600 children with infantile-onset SMA in 24 countries began treatment under such programs, the release said.

Today is thursday, September 14. I'm Mike Nace, Executive Editor of SMA News today A cocktail of two microRNAs and two transcription factors is enough to transform human skin cells directly into motor neurons, scientists report — an achievement of potentially considerable importance in understanding such motor neuron diseases as spinal muscular atrophy. Damage to motor neurons underlies several devastating and paralyzing diseases, from SMA to ALS. Scientists have struggled to grow human motor neurons in the lab for research purposes, which is one reason this work is so notable. Researchers were able to convert skin cells from healthy adults into motor neurons. Importantly, this process also didn’t require skin cells to change into stem cells before becoming motor nerve cells. In the current study, the research team further investigated the role of these microRNAs and how they help convert skin cells into motor neurons. It found that the microRNAs identified in the study assist cells in holding at a stage where they are ready to convert to neurons. But they were inactive and need more help. After extensive research, researchers identified two transcription factors — ISL1 and LHX3 — were the missing link. Once added to the mix, skin cells turned into spinal cord motor neurons in about 30 days. The four factors — microRNA-9, microRNA-124, ISL1 and LHX3 — help cells shed their skin cell “genetic identity” and embrace instructions that lead them to becoming motor nerve cells, scientists said. The converted motor neurons showed a similar genetic profile — in terms of gene activation and how they work — to mouse motor neurons. How well their genetic profile compares to human motor neurons is still a question, because these cells are very difficult to obtain from living adults. Future studies will let researchers determine how well their converted motor neurons match natural human motor neurons.

Some discouraging news for the SMA community, as, according to the results of the CARNIVAL clinical trial, Valproic acid, also known as VPA, combined with L-carnitine does not improve the survival of SMA type I patients Previous studies suggested that VPA is a potential therapeutic candidate for SMA. In the CARNIVAL Type I trial, researchers led by Boston's Massachusetts General Hospital set out to investigate the safety and therapeutic potential of VPA, combined with L-carnitine, in infants with SMA. L-carnitine is a compound involved in cellular energy production. The Phase 2 study enrolled 37 infants with SMA type I aged two weeks to 12 months from seven clinics in the United States and Canada, and one in Germany. Cure SMA and Cure SMA Canada funded the study for the North American sites. Patients completed two screening visits within a two-week period to establish disease parameters at baseline. The babies then received two daily doses of L-carnitine and VPA. Researchers measured treatment effects at three and six months and compared them to an untreated, matched disease group of 57 type I infants. They chose controls retrospectively from a larger cohort of 151 SMA type I infants enrolled in the  University of Utah's Project Cure SMA database. The study's primary endpoint was to determine the treatment's safety and adverse effects. Secondary endpoints included survival, time to death or ventilator dependence, defined as more than 16 hours of ventilator support per day. Researchers detected 245 adverse effects, mostly related to respiratory problems, in 95 percent of patients. These resulted in 14 deaths. Overall, the CARNIVAL Type I trial proves no survival benefit for infants with SMA type I treated with L-carnitine/VPA.

Spotlight Innovation has entered into a sponsored research agreement with Indiana University to develop safe and effective therapeutic options for the treatment of spinal muscular atrophy. The partnership will seek to continue development of STL-182, the company’s lead product candidate for treating SMA. STL-182 is an orally-available small molecule that has been shown to have potential therapeutic effect in the treatment of SMA. Spotlight has previously reported that STL-182 has shown the potential in SMA mouse models to restore neuromuscular function by stabilizing such SMN protein levels. Dr. Elliot Androphy, inventor of the therapy, is also the chair of the Department of Dermatology of Indiana University School of Medicine. At Indiana, Androphy has used a novel, cell-based high throughput screen for compounds that increase SMN protein levels – work that has led to the identification of pre-clinical drug candidates for SMA.

According to a new study, a molecule known as A15/283 being developed to treat SMA , has shown significant efficacy in male mouse models of the disease. A15/283 is a DNA sequence that binds to mRNAs, which are the intermediary molecules between the DNA and the protein. Since mRNAs must be single-stranded in order to become “translated” into proteins, the binding of this DNA sequence to mRNA molecules renders the mRNA unable to be turned into a protein, as the molecule is now double-stranded. Using this technique against a degradation protein that would otherwise degrade SMN will likely boost SMN levels. Researchers gave A15/283 to mouse models of SMA lacking the SMN protein once and again three days after birth. Results showed gender-specific improvement of tail necrosis in male mice. Researchers also observed a modest increase in SMN protein levels, leading to significant improvement in certain symptoms specific to SMA in mice. Researchers also concluded that early administration of A15/283 led to a near-total correction in expression levels due to increases in the SMN protein. “These results in the mouse model are very promising for the possible treatment of mild spinal muscular atrophy cases in children,” Dr. Ravindra Singh, a professor of biomedical sciences at Iowa State's College of Veterinary Medicine, said in a press release. “We’re hoping this line of research could someday lead to clinical trials, but more work remains before that can happen.”

At nine months of age, Brianna Albers was diagnosed with spinal muscular atrophy (SMA) type 2. As a 22-year-old college senior from Rosemount, Minnesota, she also struggles with social anxiety, dysthymia (mild depression), and disordered sleep. In society’s view, she says, that makes her a bit of a monster. “Disabled…