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New DMD exon-skipping therapy on the way

Following positive results obtained in Phase I/II trial of SRP-4053 (Golodirsen), Sarepta Therapeutics has announced a plan to submit a new drug application (NDA) for accelerated approval of Golodirsen in patients with Duchenne muscular dystrophy (DMD).

According to the results of the clinical study, Golodirsen significantly boosted dystrophin protein production in 25 boys with confirmed deletions of the DMD gene amenable to exon 53 skipping. This mutation affects about 8 percent of all DMD patients.


What is Golodirsen?

Golodirsen uses exon-skipping technology and works by binding to exon 53 of the dystrophin sequence to exclude, or skip, this part of the line. This helps produce a smaller but functional form of dystrophin protein.


Positive results

Golodirsen showed the potential to treat Duchenne muscular dystrophy (DMD) in the first clinical trial of DMD patients. Press release


Why do we need to skip an exon?

DMD is caused by specific errors (mutations) in the gene that codes for dystrophin. Dystrophin is a protein that plays a crucial role in the function of muscle cells and protects them from damage as muscles contract and relaxes. These mutations in the dystrophin gene lead to a lack of dystrophin protein in muscles. Without enough dystrophin, muscles gradually grow weaker until they can’t move at all, and eventually, breathing and heart function are lost.

The condition is universally fatal, and death usually occurs before the age of 30, generally due to respiratory or cardiac failure.


More about Golodirsen

Golodirsen uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO)* chemistry and exon-skipping technology to skip exon 53 of the DMD gene. Golodirsen is designed to bind to exon 53 of dystrophin pre-mRNA, resulting in exclusion, or “skipping,” of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. Exon skipping is intended to allow for the production of an internally truncated but functional dystrophin protein.

Golodirsen is one of the investigational candidates currently being evaluated in the ESSENCE study, a global, randomized, double-blind, placebo-controlled study evaluating efficacy and safety in patients amenable to skipping exons 45 or 53.

*a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule (colloquially, an oligo) used in molecular biology to modify gene expression. 


More about the clinical trial

 ESSENCE: Phase III Study

Purpose: The main objective of this study is to evaluate the efficacy of SRP-4045 and SRP-4053 compared to placebo in Duchenne muscular dystrophy (DMD) patients with out-of-frame deletion mutations amenable to skipping exon 45 and exon 53, respectively.

Location: United States, Europe, Canada, Israel

For more information, please visit www.clinicaltrials.gov or www.essencetrial.com



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Portrait of Duchenne – Exon skipping and gene therapy – Blog

Microdystrophin gene transfer trial on Hold

Solid Biosciences announces a clinical hold on SGT-001 microdystrophin gene transfer the clinical Phase I/II clinical trial for Duchenne muscular dystrophy. 

Solid Biosciences Inc. announced it had received notification from the U.S. Food and Drug Administration (FDA) that IGNITE DMD, its Phase I/II clinical trial for microdystrophin gene transfer in Duchenne muscular dystrophy (DMD), has been placed on Clinical Hold.

What happened?

The first patient dosed in the clinical trial was a non-ambulatory adolescent. Several days after administration, the patient was hospitalized due to laboratory findings that included a decrease in platelet count, followed by a reduction in red blood cell count and evidence of complement activation. *The complement system is an enzyme cascade that helps defend against infection. 

How is the patient now?

The patient was admitted to the hospital, received treatment, and he is home with his family with no symptoms.

What is a clinical hold?

Solid reported the event to the FDA and, because it was unexpected, classified it as a Suspected Unexpected Serious Adverse Reaction (SUSAR).

What’s next?

The team at Solid will be working with the principal investigator and FDA to fully understand the cause and nature of this event, as well as identify appropriate next steps as soon as possible.


In case you don’t remember the specifics about the microdystrophin and gene therapy we invite you to watch the interview we conducted in London with Dr. Jeffrey Chamberlain PH.D.:  Here


About the clinical trial:

The Phase I/II clinical trial, called IGNITE DMD, is a randomized, controlled, open-label, single ascending dose study that will evaluate the safety and efficacy of SGT-001 in both ambulatory and non-ambulatory patients with DMD.  IGNITE DMD, adaptive in nature, will allow Solid Biosciences to adjust dose and number of patients as the study progresses to characterize the safety and efficacy of SGT-001 efficiently. The patient screening will begin at their first participating study in one location in the United States in the coming days. Solid Biosciences is working to bring on additional sites in the United States and abroad.

About SGT-001

SGT-001 is a novel adeno-associated virus* (AAV) vector-mediated gene transfer under investigation for its ability to address the underlying genetic cause of DMD. SGT-001 is a systemically administered* candidate that delivers a synthetic dystrophin gene, called microdystrophin, to the body. This microdystrophin encodes for a functional protein surrogate that is expressed in muscles and stabilizes essential associated proteins.


  • Clinical trial: Here
  • Letter to the Duchenne Community About the Status of the IGNITE DMD Clinical Trial: Here
  • Link to the press release: Here
  • More info on our previous blog post: Here

Canadian Research osteoprotegerin (OPG)

Meeting with professor Jérôme Frenette about osteoprotegerin (OPG).

We are producing a video series of interviews with Canadian researchers working on DMD. We have met many professors, and our videos will be coming up soon.  We wish to connect you, the DMD community, with the professors. You will be delighted to know their deepest motivation and devotion. They love to know your face; you are the people that will be impacted by their discovery. Also, the video is a very good medium to offer an understanding of scientific concepts which are not always so easy to grasp.


Video series coming up…

We met and interviewed professor Jérôme Frenette of the Rehabilitation Department of Laval University who is currently working on a potential treatment for Duchenne muscular dystrophy. He presented some very promising work with his team at the University Hospital Center of Quebec on osteoprotegerin (OPG).


Interesting information about OPG

• OPG is a protein well known for its protective role against osteoporosis, where its name comes from, osteoprotegerin.
• OPG reduces damage and inflammation.
• OPG eases Duchenne muscular dystrophy, especially in fast-twitch skeletal muscle.
• OPG can simultaneously treat osteoporosis and muscle degeneration in patients with DMD.
• Dystrophic muscles can be protected without correcting the dystrophin gene. The team from the Faculty of Medicine at Laval University in Quebec City has just demonstrated that this protein could be a new avenue of treatment for Duchenne muscular dystrophy (DMD).


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