SGT-001 Showing Positive Trends in Duchenne Muscular Dystrophy

The microdystrophin gene transfer therapy from Solid Biosciences has shown protein expression in the first 3 patients dosed. As a result, the company is expediting the planned dose-escalating activities.

Ilan Ganot

Ilan Ganot, MBA, the co-founder, chief executive officer, and president of Solid Biosciences

Ilan Ganot, MBA

Preliminary findings from the IGNITE-DMD trial have shown positive signs for Solid Biosciences’s microdystrophin gene transfer therapy, SGT-001, which have led to the company’s desire to dose escalate as planned and as soon as possible, Solid announced.1

The phase 1/2 dose-ascending trial is evaluating the safety and efficacy of the gene therapy in Duchenne muscular dystrophy (DMD). The initial 3-month biopsy data from the first 3 patients dosed showed levels of micro-dystrophin protein expression. Solid is currently “engaging with the appropriate parties” to move things forward.

“We believe that SGT-001 will be a meaningful treatment for patients with DMD and are confident we have the right approach in place to evaluate its potential at higher doses. We have already begun working to expedite the planned dose escalation strategy outlined in our clinical trial protocol,” Ilan Ganot, MBA, the co-founder, chief executive officer, and president of Solid Biosciences, said in a statement. “This strategy is further supported by our scalable manufacturing process, from which we have sufficient drug product available to dose escalate without delay. We have the financial resources to execute on our plan and look forward to communicating additional data later this year.”

All 3 patients were dosed with 5E13 vg/kg of SGT-001, the lowest dose in the study protocol. In a single patient, microdystrophin was detected via western blot below the 5% level of quantification of the assay, and via immunofluorescence in approximately 10% of fibers.

A spokesperson from Solid Biosciences told NeurologyLive that SGT-001 is based on more than 30 years of research by researchers Jeffrey S. Chamberlain, PhD, a professor in the Departments of Neurology, Medicine, and Biochemistry, the McCaw Endowed Chair in Muscular Dystrophy at the University of Washington School of Medicine, and the director of the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center of Seattle, and Dongsheng Duan, PhD, the Margaret Proctor Mulligan Professor in Medical Research at the University of Missouri.

“Specifically, only our SGT-001 microdystrophin transgene includes the binding domain for neuronal nitric oxide synthase, or nNOS. This is a key differentiator because in preclinical studies the proper localization of nNOS has been demonstrated to prevent exercise-induced fatigue, ischemia, and edema,” the spokesperson said.

There were signs of co-localization of nNOS and beta-sarcoglycan related to microdystrophin expression in the first patient. In the second and third patients, microdystrophin was detected via immunofluorescence at low levels but was undetectable via western blot.

SGT-001 is a novel adeno-associated viral (AAV) vector-mediated gene therapy which is a systemically administered candidate that delivers microdystrophin to the body. SGT-001 utilizes AAV9, which has an affinity for muscle and is currently being evaluated in multiple clinical programs in other indications.

IGNITE DMD is a randomized, controlled, open-label, single-ascending-dose clinical trial, and is the only clinical trial for a systemic microdystrophin gene therapy that is evaluating safety and efficacy in both ambulatory children and non-ambulatory adolescents, according to Solid Biosciences. Participants in the trial will be randomized to either the active treatment group or the delayed treatment control group, where those who continue to meet the study’s treatment criteria will receive active treatment after 12 months. Thus far, 6 patients have been enrolled, 3 in the active group and 3 in the delayed treatment group.

The primary objectives of the study are to assess the safety and tolerability of SGT-001, as well as its efficacy, as defined by microdystrophin expression. According to the Solid spokesperson, IGNITE-DMD will also explore “muscle function and mass, respiratory and cardiovascular function, serum and muscle biomarkers associated with microdystrophin production, patient-reported outcomes, and quality of life measures, among other endpoints.”

“The patients who have received SGT-001 as part of the IGNITE DMD clinical trial are all doing well, and we are encouraged to explore higher doses moving forward,” said Barry Byrne, MD, PhD, a professor of pediatrics at the University of Florida, the director of the UF Powell Gene Therapy Center, and principal investigator for IGNITE DMD. “It is extremely important to advance innovative research with the ultimate goal to bring therapies to patients with Duchenne muscular dystrophy.”


1. Solid Biosciences Announces Preliminary SGT-001 Data and Intention to Dose Escalate in IGNITE DMD Clinical Trial for Duchenne Muscular Dystrophy [press release]. Cambridge, MA: Solid Biosciences; Published February 7, 2019. Accessed February 7, 2019.

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