Nav: Home

New drug for Duchenne muscular dystrophy clears phase 1 clinical trial testing in boys

February 21, 2019

Amsterdam, February 21, 2019 - Patients with Duchenne muscular dystrophy (DMD) have few treatment options. Medications currently available or in development either target only a subset of DMD patients with a particular genetic mutation or cause significant side effects. The investigational drug edasalonexent, an oral NF-κB inhibitor, has the potential to slow the progression of the disease for all patients with DMD. The results of a Phase I clinical trial published in the Journal of Neuromuscular Diseases indicate that the drug was well tolerated with no safety issues in boys with DMD, paving the way for further clinical testing.

"In addition to being well tolerated in pediatric patients with DMD, our Phase 1 data demonstrated that edasalonexent (CAT-1004) inhibited NF-κB. This is important because NF-κB is a key link between the loss of dystrophin and disease progression in DMD. This would mean that edasalonexent has the potential to limit disease progression for all patients affected by DMD, regardless of their underlying mutation," explains Joanne Donovan, MD, PhD, Chief Medical Officer of Catabasis Pharmaceuticals, Inc. (Cambridge, MA, USA).

Edasalonexent is an orally administered small molecule that contains two active substances, salicylic acid and the omega-3 fatty acid docosahexaenoic acid (DHA), which are linked together to produce a unique molecule. Both of these molecules are inhibitors of NF-kB, but edasalonexent inhibits NF-kB much more potently than either of the base molecules alone.

In a previous study, edasalonexent was well tolerated and absorbed in adults and inhibited NF-κB. The goal of the current study, a Phase 1/2 study known as MoveDMD, was to evaluate the effects in children with DMD. In this one-week, open-label, multiple-dose Phase 1 clinical trial, 17 boys (mean age 5.5 years) were administered three sequential ascending doses of edasalonexent (33, 67, and 100 mg/kg/day). All doses were found to be well tolerated with no serious adverse events, dosing interruptions, dose reductions or discontinuations due to adverse events. Most adverse events were mild and gastrointestinal.

Importantly, for the two higher doses (67 and 100 mg/kg/day), seven days of treatment resulted in decreased levels of NF-κB-regulated genes, as measured by whole-blood mRNA sequencing. The treatment also reduced levels of serum proteins thought to originate from damaged muscles. "This shows that with short-term dosing, edasalonexent can directly reduce the levels of elevated NF-κB in circulating DMD mononuclear cells prior to any changes observable in muscles," notes Dr. Donovan.

Because of the potential universal benefit of edasalonexent for all types of DMD, Dr. Donovan suggests it could be used either alone or in combination with other medications including gene therapeutic approaches currently under development. Edasalonexent can potentially reduce muscle inflammation and degeneration and enhance muscle regeneration. She also suggests that inhibition of NF-κB may have disease-modifying effects.

"The data from the Phase 1 MoveDMD clinical trial reinforce the good tolerability and safety profile of edasalonexent that we have now also observed in the Phase 2 trial and open-label extension," adds Erika Finanger, MD, Associate Professor of Pediatrics, Division of Neurology, School of Medicine at Oregon Health & Science University and principal investigator for both the MoveDMD and PolarisDMD trials. "I am pleased to continue to evaluate edasalonexent as a potential novel therapy for those affected by Duchenne, and I am excited to participate in the Phase 3 Polaris DMD study."

DMD is the most common genetic neuromuscular disease, affecting one in 3,500-6,000 male births. The disease is characterized by progressive muscle weakness and degeneration with loss of contractibility. It is caused by one of several mutations in the DMD gene. No matter what the particular mutation, a key driver of muscle degeneration and suppression of muscle regeneration in DMD is chronic activation of the transcription factor NF-κB, which causes loss of dystrophin, a protein which helps keep muscle cells intact.
-end-


IOS Press

Related Genetic Mutation Articles:

New research uncovers how common genetic mutation drives cancer
A new, multicenter study led by Fred Hutchinson Cancer Research Center and Memorial Sloan Kettering Cancer Center determined how a single mutation in splicing factor 3b subunit 1 (SF3B1), the most frequently mutated splicing factor gene, drives the formation of many cancers.
Genetic mutation appears to protect some people from deadly MRSA
An inherited genetic tendency appears to increase the likelihood that a person can successfully fight off antibiotic-resistant staph infections, according to a study led by Duke Health researchers.
Genetic mutation linked to flu-related heart complications
For the first time, research in mice has shown a link between a genetic mutation, flu and heart irregularities that researchers say might one day improve the care of flu patients.
Treatment targeted at a genetic mutation relieves psychosis symptoms
Treatment of psychosis can be targeted to a specific genetic mutation in patients with psychotic disorders, according to a study in Biological Psychiatry, published by Elsevier.
Cardiac genetic mutation may not always predict heart disease
One in 10 people with this condition were born with a mutation in the TTN gene, but -- until now -- it has been unclear whether everyone with these mutations will inevitably develop dilated cardiomyopathy.
Researchers discover genetic mutation behind serious skull disorder
An international collaboration has identified a new genetic mutation behind the premature fusing of the bony plates that make up the skull.
NUP160 genetic mutation linked to steroid-resistant nephrotic syndrome
Mutations in the NUP160 gene, which encodes one protein component of the nuclear pore complex nucleoporin 160 kD, are implicated in steroid-resistant nephrotic syndrome, an international team reports March 25, 2019, in JASN.
Study identifies genetic mutation responsible for tuberculosis vulnerability
Scientists discovered a genetic variant that greatly increases a person's likelihood of developing tuberculosis.
Scientists develop method to visualize a genetic mutation
A team of scientists has developed a method that yields, for the first time, visualization of a gene amplifications and deletions known as copy number variants in single cells.
Genetic mutation drives tumor regression in Tasmanian Devils
Washington State University scientists have discovered genes and other genetic variations that appear to be involved in cancerous tumors shrinking in Tasmanian devils.
More Genetic Mutation News and Genetic Mutation Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.