Throughout 2019, Muscular Dystrophy News Today brought you daily coverage of important discoveries, treatment developments, clinical trials, and other important events related to muscular dystrophy.
As we look forward to bringing you more news this year, we present the 10 most-read stories of 2019.
In May, Muscular Dystrophy News Today reported Sarepta Therapeutics’ acquisition of an investigational gene therapy program focused on calpain-3 for the treatment of limb-girdle muscular dystrophy type 2A (LGMD2A). Calpain-3 is an enzyme that does not work properly in people with LGMD2A, leading to the accumulation of toxic waste proteins within skeletal muscles, which ultimately compromises their function. The calpain-3 gene therapy program uses a rhesus monkey-derived viral vector to deliver a functional copy of the calpain-3 gene (CAPN-3) to the patients’ skeletal muscles, with the intention of preventing further deterioration. This program was originally developed by the Research Institute at Nationwide Children’s Hospital.
In August, Muscular Dystrophy News Today interviewed Claudia Senesac, PhD, a physical therapist who has been working with boys with Duchenne muscular dystrophy (DMD) for nearly 40 years, to discuss the benefits and importance of physical therapy for DMD. Senesac noted the importance of being reasonable about the amount, intensity, and type of exercises that boys with DMD should perform to slow muscle degeneration. She said that stretching exercises, swimming, and night splints (braces worn overnight) are particularly helpful to improve range of motion, and recommended that parents look for physical therapists who are experienced in working with children with DMD.
We covered the release in October of new nine-month data from a Phase 1/2 trial (NCT03652259) investigating the safety, tolerability, and efficacy of SRP-9003 (MYO-101), a form of gene therapy developed by Sarepta Therapeutics, in children with limb girdle muscular dystrophy type 2E (LGMD2E). SRP-9003 uses a viral vector to deliver a functional copy of the beta-sarcoglycan gene (SGCB), which is defective in people with LGMD2E, directly to their muscles to halt and possibly reverse the symptoms of the disease. Nine-month data from the study showed that a single administration of SRP-9003 at a low dose of 5×1013 vg/kg reduced the levels of creatine kinase (a marker of muscle damage) by 82%, and led to significant improvements in several functional measures in three children with LGMD2E who were part of the study’s first patient group. Sarepta is planning to test a higher dose of SRP-9003 in the second cohort of patients participating in the trial. The study is expected to enroll a total of nine children with LGMD2E, ages 4 to 15, and to conclude on Dec. 31, 2020.
In February, we covered preliminary data from a Phase 1/2 trial (NCT03368742) investigating the safety, tolerability and efficacy of the experimental gene therapy SGT-001 in children and teenagers with DMD. SGT-001, developed by Solid Biosciences, uses a viral vector to deliver a gene producing a short, artificial form of dystrophin, called microdystrophin, into muscle cells. Microdystrophin has the key components of the normal protein missing in those with DMD. Three-month data from the IGNITE DMD study showed that a single administration of SGT-001 at the lowest planned dose (5E13 vg/kg) led to the detection of microdystrophin in some muscle fibers of the first three boys treated. The study has since been placed on a second clinical hold by the U.S. Food and Drug Administration (FDA) after a boy who received SGT-001 in the study experienced a severe adverse event. Solid is now working closely with the FDA to lift the hold.
Fulcrum Therapeutics announced in April that it had acquired the global rights to develop and potentially market losmapimod, an investigational treatment for facioscapulohumeral muscular dystrophy (FSHD). Losmapimod, originally developed by GlaxoSmithKline for other indications, is currently being investigated as a treatment for FSHD due to its ability to reduce the abnormal the activity of DUX4, the gene that causes the disease. Two Fulcrum-sponsored Phase 2 trials — NCT04003974 (still recruiting) and NCT04004000 — are currently underway to investigate the safety and efficacy of losmapimod in patients with FSHD1.
In May, Grace Pavlath, MD, chief research officer at the Muscular Dystrophy Association, and Barry Byrne, MD, a pediatric cardiologist and director of the University of Florida’s Powell Gene Therapy Center, discussed the therapeutic potential of gene therapies to treat DMD. Experts believe that a cure for DMD may be found soon in a gene therapy similar to Novartis‘ Zolgensma, which was the first gene therapy approved by the FDA to treat all types of spinal muscular atrophy in newborns and toddlers up to age 2. They also noted the high manufacturing costs of these therapies are a major drawback that must be addressed to make them more broadly available.
Investigators from the University of Texas Southwestern Medical Center showed that the CRISPR-Cas9 gene editing tool could be used to correct a common mutation in the dystrophin (DMD) gene that is associated with DMD. In the study, this gene editing tool was able to correct defects in DMD known to occur in patients, and to restore the production of dystrophin in heart muscle cells (cardiomyocytes) derived from stem cells of DMD patients and in mice with the disease. Based on these findings and other achievements, Parent Project Muscular Dystrophy awarded a grant worth $250,000 in 2017 to the team of scientists led by professor Eric Olson to advance their research into CRISPR as a DMD treatment strategy. Olson, supported by Cure Duchenne Ventures and others, also co-founded a company aiming to use this gene editing tool in developing a therapy.
Researchers from Duke University found that a single dose of a gene therapy based on the CRISPR-Cas9 gene editing technology could be sufficient to treat DMD in the long term or even permanently. In their study, they injected a single dose of the therapy into adult and newborn mice with DMD. Using this approach, they managed not only to stimulate the production of functional dystrophin in the animals’ muscles as early as eight weeks after treatment, but also to keep it stable for at least one year. Some adult animals ended up developing an immune response against the therapy’s constructs, which was avoided in newborn animals that were treated with immunosuppressive agents while they received the gene therapy. According to the researchers, these preliminary findings demonstrate that gene therapies based on the CRISPR-Cas9 gene editing tool may correct genetic defects permanently.
In February, Muscular Dystrophy News Today interviewed several men living with DMD after the age of 30 to gain insight into their day-to-day lives and the personal challenges they faced since being diagnosed. While luck seems to play a role in their longevity, access to adequate treatment and medical professionals, support from caregivers and friends, and a positive attitude towards life also had significant impacts on their lifespan.
Nine-month data from a Phase 1/2 trial (NCT03375164) testing Sarepta Therapeutics’ microdystrophin gene therapy showed that the treatment increased the levels of dystrophin by 81.2% in the muscles of four boys with DMD without signs of adverse effects. The therapy also led to significant improvements in motor function, including the ability to stand and to shift from a lying to a sitting position. The gene therapy, called AAVrh74.MHCK7.micro-dystrophin, uses a viral vector to deliver microdystrophin, a short form of dystrophin, to muscle cells. Following the promising findings in this trial, called Study 101, Sarepta will conduct a Phase 2 trial known as Study-102 (NCT03769116). This trial is currently recruiting participants at two sites in the U.S. It is expected to enroll approximately 24 boys with DMD, ages 4 to 7.
At Muscular Dystrophy News Today, we hope these stories and our reporting throughout 2020 contribute to informing and improving the lives of everyone affected by MD.
We wish all our readers a happy 2020.