Progress Now Fall 2014

Research updates and clinical trials information

by Quest Staff on October 30, 2014 - 9:01am

Quest Fall 2014

Readers sometimes wonder what’s happening with research for their diseases when they don’t see news about them for a while in the pages of Quest. But keep in mind: Research that seems to be for one disorder often has spillover implications for others.

In this issue: Understanding how the CoughAssist affects clearance of secretions in congenital muscular dystrophy and limb-girdle muscular dystrophy may have implications for its use in other muscle diseases. And developing exon skipping for Duchenne muscular dystrophy is likely to provide a foundation for moving this strategy forward in other genetic disorders.

To learn more about the diseases in MDA’s program, go to the online disease directory. And to stay on top of the latest research developments and news, be sure to visit

Stem Cells Study

Determining the effects of stem cells from ALS patients’ own bone marrow cells

Israeli biotechnology company BrainStorm has begun testing adult stem cells derived from patients’ own bone marrow tissue in 48 people with amyotrophic lateral sclerosis (ALS) in three U.S. sites. ALS is a disorder in which motor neurons — cells in the spinal cord and brain that control muscle movement — degenerate, leading to weakness and, eventually, paralysis, along with difficulty speaking, swallowing and breathing. Encouraging interim results have been reported from two earlier trials of BrainStorm’s patented NurOwn stem cells conducted outside the U.S. The cells appear to be safe and well-tolerated when injected into muscle tissue or spinal fluid, and more trial participants have stabilized or improved during the after-treatment period than they did before the treatment. 

Participants in the U.S. trial must have ALS; be 18–75 years old; have had onset of symptoms within the previous two years; have a respiratory capacity that is at least 65 percent of normal; live near Boston or Worcester, Mass., or near Rochester, Minn.; and meet other criteria. For details, enter NCT02017912 in the search box at

A First for DMD

Ataluren receives conditional approval in the EU, phase 3 trial underway in the United States 

The investigational oral drug ataluren, in development to treat Duchenne muscular dystrophy (DMD) resulting from a specific type of genetic mutation, has received conditional approval in the European Union (EU), where it will be marketed under the trade name Translarna. 

This designation means patients can receive it in the EU and EU-associated countries while additional studies are being conducted. This is the first time a drug specifically developed for DMD has received an approval.

Ataluren is being developed by New Jersey-based PTC Therapeutics. MDA gave PTC a grant for $1.5 million in 2005 and has supported laboratory development of “stop codon read-through” strategies since 2003.

The drug is not available in the U.S. A multinational, 220-person, phase 3 trial of ataluren that includes several locations in the U.S. is active but no longer accepting participants. The trial includes those who have a premature stop codon in the dystrophin gene as determined by genetic testing.

For details, enter NCT01826487 in the search box at To find out about genetic testing for this and other trials, talk with your MDA clinic physician or genetic counselor.

Expectations for Eteplirsen

Sarepta to submit a new drug application to the FDA by the end of the year

After nearly three years (144 weeks) of treatment with the experimental drug eteplirsen, in development by Massachusetts-based Sarepta Therapeutics, 12 boys with DMD have continued to show benefits on tests of respiratory function and/or walking distance compared to what would be expected from the natural history of the disease. The intravenous drug also appears to be safe and well-tolerated.

A phase 3 U.S.-based trial to continue testing the drug has launched and recruitment is underway. Additionally, by the end of 2014, Sarepta intends to submit a new drug application to the U.S. Food and Drug Administration (FDA) for eteplirsen to treat patients with DMD due to specific genetic mutations. The company hopes to use the FDA’s accelerated approval pathway, which would allow qualified patients to have access to the drug before confirmatory studies are completed. 

Since the 1990s, MDA has provided funding for laboratory testing of the strategy that underlies eteplirsen. It also has provided supplemental funding for human testing of this drug. Eteplirsen targets a section of the dystrophin gene known as exon 51 and is designed to treat DMD patients with dystrophin gene mutations near this section. The disease is caused by mutations near exon 51 in about 13 percent of patients. Sarepta also is developing drugs that target exons 45 and 53 to treat patients with mutations near those sections of the dystrophin gene. Two additional U.S.-based eteplirsen trials are expected to open in 2015.

For details and a list of study sites with contact information, enter NCT02255552 in the search box at Or contact Celeste DiJohnson or Charlene Brathwaite at, or call 855-363-7547. 

Muscle Maintenance

Akashi Therapeutics’ HT-100 receives FDA ‘fast track’ designation

The experimental DMD drug HT-100, in development by Massachusetts-based Akashi Therapeutics with support from MDA, has shown encouraging preliminary results in a 17-person trial and has received “fast track” designation from the U.S. Food and Drug Administration (FDA). Fast track is a mechanism that the FDA can use to speed up its review of experimental drugs for serious or life-threatening disorders when there is early evidence that a new medication may provide benefit over available therapies. 

HT-100 is an oral compound that is intended to reduce inflammation and scar tissue formation and promote regeneration in DMD-affected muscles. The drug appears to be safe, and signs that the drug may be working as intended have been seen. HT-100 does not target specific mutations in the dystrophin gene, making it potentially useful for all patients with DMD.

The current trial of HT-100 is closed to new participants, but Akashi can be contacted with questions at or (617) 431-7250. Email is preferred.

Steroids Without Side Effects?

MDA-supported drug VBP15 aims to replicate corticosteroids without unwanted effects

Funding from MDA and three other organizations to ReveraGen BioPharma of Silver Spring, Md., will support a planned phase 1 trial in healthy volunteers of Reveragen’s experimental drug for DMD, VBP15. VBP15 is intended to replicate the benefits of corticosteroid drugs like prednisone, prednisolone and deflazacort, which are widely used to prolong walking ability in DMD but which have many unwanted effects. The goal of VBP15’s developers is to keep the benefits of corticosteroids but reduce or eliminate the side effects.

Benefits of corticosteroids (also known as glucocorticoids) in DMD are thought to be dampening of muscle inflammation and stabilization of muscle-fiber membranes. Among the unwanted side effects that accompany chronic use of corticosteroids are: slowing of growth, weight gain, thinning of the bones and skin, high blood pressure, cataracts, suppression of the immune system and mood changes.

If VBP15 is found to be safe and well-tolerated in healthy people, the next step is likely to be a trial of the drug in people with DMD.

Check and for updated information on VBP15 testing.

Immune System Suppression

Arthritis drug in phase 2 trial for MG application

A multicenter, phase 2 trial of the intravenous drug rituximab (Rituxan) in adults with myasthenia gravis (MG) is underway and open to new participants. Rituximab suppresses a specific part of the body’s immune system and is approved by the U.S. Food and Drug Administration (FDA) to treat rheumatoid arthritis and other disorders. 

In MG, an “autoimmune” disease, the body’s immune system mistakenly attacks the parts of muscle cells that receive signals from nerve cells, resulting in fluctuating weakness that ranges from mild to severe and can even be life-threatening.

MG is currently treated with medications that prolong chemical signals from the nervous system and with drugs that suppress the immune system, particularly corticosteroid medications, such as prednisone. However, corticosteroids often only partially control the disease and can have serious side effects when used for long periods of time. The goal of this new study is to see whether rituximab can reduce the amount of the corticosteroid prednisone that MG patients require and do so safely. The trial is supported by the NeuroNEXT research network, part of the U.S. National Institutes of Health (NIH).

Participants in the rituximab trial must be 21–90 years old, have generalized MG, have been on a stable dose of prednisone for at least four weeks prior to screening and meet other criteria. For details and a list of study sites with contact information, enter NCT02110706 in the search box at Or contact Hong Vu at Yale University at or (203) 737-6385.

Making ‘Antisense’

Experimental MMD1 drug ISIS-DMPKRx being tested in healthy volunteers

California-based Isis Pharmaceuticals is testing its experimental drug for type 1 myotonic muscular dystrophy (MMD1 or DM1) in healthy volunteers and plans to begin testing it in people with MMD1 in late 2014.

The drug, known as ISIS-DMPKRx, targets the underlying molecular defect (an abnormal expansion in the DMPK gene) that is the root cause of MMD1. Isis is developing the compound in collaboration with Massachusetts-based Biogen Idec.

MDA has funded multiple studies to understand the underlying cause of MMD1 and has supported laboratory development of the strategy — “antisense” technology for MMD1 — on which ISIS-DMPKRx is based. Antisense can be made to target and then block or destroy harmful genetic instructions, such as those that cause MMD1.

Information about the ISIS-DMPKRx trial in people with MMD1 will be posted on and on as it becomes available.

Better Genetic Instructions

Isis to test experimental SMA drug ISIS-SMNRx in infants with the disorder

Isis Pharmaceuticals, the same company that is developing ISIS-DMPKRx for MMD1, is now testing its experimental drug ISIS-SMNRx in a phase 3 trial in infants with spinal muscular atrophy (SMA), a muscle-weakening disease that results from loss of nerve cells in the spinal cord.

ISIS-SMNRx, like ISIS-DMPKRx, is based on “antisense” technology. In SMA, however, the purpose of the antisense drug is a bit different from its purpose in MMD1. In SMA, the goal of the antisense compound is to change the way genetic instructions are read so that a useful form of the SMN protein — deficient in SMA-affected cells — can be produced. 

MDA has funded laboratory development of antisense for SMA, as well as many studies to understand the genetic underpinnings of this disease.

ISIS-SMNRx has shown encouraging results in two earlier (phase 2) studies in infants and children with SMA. Both these studies are closed to new participants, but Isis plans to start a large-scale trial of ISIS-SMNRx in SMA-affected children (not infants) later in 2014.

Participants in the phase 3 trial of ISIS-SMNRx in infants must be 7 months old or younger, have two copies of the SMN2 gene, live near a study site and meet additional criteria. For details, including study sites and contact information, enter NCT02193074 in the search box at Additional information can be found on the Isis site at, particularly at Watch, and for updates.

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