Progress Now Spring 2015

Research and clinical trial updates

by Quest Staff on April 21, 2015 - 9:03am

Quest Spring 2015

MDA welcomes two new muscle disease and ALS experts

As part of MDA’s bold plan to accelerate treatments and cures for neuromuscular diseases, two new scientific program officers have joined the MDA family: Amanda Haidet-Phillips, Ph.D.,
and Laura Hagerty, Ph.D. Under the leadership of MDA Senior Vice President and Scientific Program Director Grace Pavlath, Ph.D., they will help drive discoveries for neuromuscular and motor neuron diseases.

“We are thrilled to have Amanda and Laura on our team. Their depth of clinical and scientific knowledge will enable MDA to accelerate progress for the families we serve and the larger research community,” says Valerie A. Cwik, M.D., MDA Executive Vice President and Chief Medical and Scientific Officer.

Haidet-Phillips comes to MDA from Johns Hopkins University, where she was a postdoctoral fellow in the lab of Nicholas Maragakis, a renowned ALS researcher and clinician. Prior to Johns Hopkins University, she completed her doctoral studies in The Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital in Columbus, Ohio. Her area of focus is motor neuron and nerve diseases, including ALS, SMA and spinal-bulbar muscular atrophy (SBMA).

“MDA’s mission is one that I have been working toward my entire career — to find treatments and cures to combat the devastating effects of motor neuron diseases,” Haidet-Phillips says. “I’ve had the opportunity to learn from renowned and respected leaders in the ALS research field while making significant contributions, and I look forward to helping MDA achieve its mission.”

Hagerty joins MDA from GlaxoSmithKline, where she was an investigator within its Skeletal Muscle Metabolism Discovery Unit. As a muscle physiologist with over seven years of combined research experience in the pharmaceutical and biotechnology industries, she has worked to develop treatments for DMD and other neuromuscular disorders. She earned her doctorate in pharmacology, with a certificate in biological chemistry from Duke University. Her concentration on MDA’s research team will consist of a portfolio of muscle diseases, including DMD. 

“I am honored and excited to join an organization that has played a major role in neuromuscular disease research breakthroughs,” Hagerty says. “In my work developing treatments for DMD, I have seen firsthand what a promising time this is for muscular dystrophy research. I look forward to applying my skill set in working directly with the communities who will benefit from these treatments.”

Betting on Bone Marrow

Trial testing modified bone marrow stem cells from people with ALS encourages investigators

In January, BrainStorm Cell Therapeutics announced encouraging results from its phase 2a clinical trial of NurOwn cells in amyotrophic lateral sclerosis (ALS), conducted in Jerusalem. NurOwn cells are taken from bone marrow tissue of people with ALS and then modified in a laboratory to secrete nerve-nourishing proteins. It is hoped these proteins will help protect muscle-controlling nerve cells, thereby prolonging muscle function and survival. The company said nearly all of the 14 trial participants experienced a decline in how quickly the disease progressed, as assessed by the ALS Functional Rating Scale or a respiratory measurement known as forced vital capacity. After laboratory modification, the participants received injections of their own cells into a muscle and into their spinal fluid, at a single time point.

BrainStorm is now testing its NurOwn cells at centers in Boston and Worcester, Mass., and in Rochester, Minn. Participants will be randomly assigned to receive simultaneous injections of NurOwn cells or a placebo into a muscle and into their spinal fluid, at a single time point.

Participants in the U.S. NurOwn trial must be 18–75 years old, have had ALS symptoms for no more than two years and meet other criteria. To learn more, enter NCT02017912 in the search box at For more about BrainStorm’s research, visit

Antioxidant Study

NIH testing whether FDA-approved drug also can benefit CCD 

The National Institute of Nursing Research (NINR) at the National Institutes of Health (NIH) is conducting a study to determine if an antioxidant drug that has been approved by the FDA for other indications can reduce the severity of some symptoms in people with central core disease (CCD), a disorder associated with weakness and susceptibility to dangerous anesthesia reactions known as “malignant hyperthermia.”

The antioxidant study, which is being conducted in Bethesda, Md., involves three outpatient visits of four to six days each to the NIH campus during the course of a year. Each participant will be assigned to receive either the study drug or a placebo three times a day for six months. Costs for all study-related tests, as well as travel and accommodations, are covered by the study. Antioxidants interfere with a chemical reaction called “oxidation,” which can damage cells.

Participants in the antioxidant trial must have a diagnosis of CCD, be at least 7 years old, be able to walk, have had a muscle biopsy and meet other criteria. For details, contact Irene Arveson at NIH at or (301) 451-4881.

New Guideline for CMD Diagnosis and Care

A committee convened by the AAN has published new recommendations

This spring, the American Academy of Neurology (AAN) released a guideline for the diagnosis and care of children with congenital muscular dystrophy (CMD), a group of early-onset, genetic disorders that can involve skeletal (including respiratory) muscle weakness, heart problems, brain and eye abnormalities, and contractures (frozen joints).

Traditionally, CMD was defined as a form of muscular dystrophy in which symptoms develop within the first year of life, but the AAN suggests that the term be broadened to include muscular dystrophies with symptoms that begin within the first two years of life.

The guideline advises doctors to monitor CMD patients for heart and respiratory abnormalities, as well as mobility impairment, swallowing difficulties and the possible need for special education, and to take precautions when a child with CMD requires anesthesia.

The new guideline for CMD diagnosis and care is based on a review of the medical literature by a panel of specialists that included several MDA-associated clinicians. It was published March 30, 2015, in the journal Neurology and is posted on the AAN website.

Cautious Optimism

BioMarin acquisition of Prosensa may accelerate development of exon-skipping drugs for DMD

Dutch biotechnology company Prosensa, developer of exon 51-targeting drisapersen and other exon-skipping drugs for Duchenne muscular dystrophy (DMD), began submitting its new drug application for drisapersen to the FDA in October 2014, via the agency’s accelerated approval process. Exon-skipping drugs are designed to allow muscle fibers to make functional dystrophin protein, which, it is hoped, will prolong muscle function and possibly survival. A phase 3 extension study of drisapersen in boys with DMD who have been in a previous drisapersen trial is open in the U.S. and Canada.

In November, Prosensa also announced that it had been acquired by the multinational company BioMarin, which may accelerate movement of its experimental compounds through
the drug-development pipeline. Prosensa also is testing PRO045, which targets exon 45 of the dystrophin gene, and PRO053, which targets exon 53, outside the U.S.

For details of the North American extension study of drisapersen in boys with DMD who have been in a previous drisapersen trial, enter NCT01803412 in the search box at For details of the non-U.S. PRO053 trial, enter NCT01957059. For the non-U.S. PRO045 trial, enter NCT01826474. 

Exon-Skipping Drug Trials Open

Sarepta testing two drugs, targeting dystrophin gene exons 51 and 53, respectively

In January, Sarepta Therapeutics reported that six boys with DMD who were treated continuously with the company’s experimental drug eteplirsen for three years walked farther in six minutes than those who had received a placebo for the first six months of the study and then got eteplirsen. Continued stability of respiratory muscle function also was reported. Eight boys were originally in the continuous treatment group, but two stopped walking very early in the study, so they could not be included in walking distance results. All 12 trial participants were included in the respiratory evaluations.

Eteplirsen is an exon-skipping drug, designed to target and block a section of the dystrophin gene known as exon 51. In patients with mutations near (but not in) dystrophin exon 51, it has the potential to allow production of functional dystrophin protein, a lack of which is the underlying cause of DMD.

Principal investigator Jerry Mendell is a longtime MDA research grantee and directs the MDA Clinic at Nationwide Children’s Hospital in Columbus, Ohio.

Sarepta plans to submit an application for approval of eteplirsen to the FDA in mid-2015. In the meantime, it is conducting a phase 3, confirmatory trial of eteplirsen in boys with DMD who can walk and have specific mutations near dystrophin exon 51, as well as a safety study in boys and young men who are no longer walking and have mutations near this exon.

Also in January, Sarepta announced that it had begun dosing trial participants with DMD caused by specific mutations near (but not in) exon 53 of the dystrophin gene with its experimental drug SRP-4053. This trial is being conducted in Europe.

For details about the phase 3 trial of eteplirsen in ambulatory boys, enter NCT02255552 in the search box at For details about the safety study of eteplirsen in boys and young men who are no longer walking, enter NCT02286947. For details about the SRP-4053 trial in Europe, enter NCT02310906. For more about Sarepta’s drug development work targeting exon 51 and other parts of the dystrophin gene, visit

Releasing A Brake on Muscle Growth

Pfizer testing its experimental myostatin inhibitor in a phase 2 trial in DMD

Pharmaceutical company Pfizer is testing its experimental compound PF-06252616 in a phase 2 trial involving 105 boys with DMD who are 6–9 years old, able to walk and meet other criteria. The drug is designed to block a protein called myostatin that limits muscle growth. By blocking it, Pfizer hopes it will increase muscle mass and improve function for boys with DMD. Test sites are open in Baltimore and Cincinnati, and additional U.S. and non-U.S. sites are planned. 

The Pfizer trial is not funded by MDA, but MDA is a longtime supporter of myostatin inhibition as a potential treatment for DMD and other muscular dystrophies. A current MDA grant to Tom Thompson at the University of Cincinnati for studies of how proteins neutralize myostatin may reveal additional possibilities for this approach.

For details about the PF-06252616 trial, enter NCT02310763 in the search box at For more about MDA-supported research to inhibit myostatin, read
In Focus: Preserving and Building Muscle Fibers.

Determining Deflazacort’s Effects

A corticosteroid drug similar to prednisone receives FDA ‘fast track’ designation

Marathon Pharmaceuticals announced in January that it has received FDA “fast track” designation for development of the corticosteroid drug deflazacort to treat DMD. Fast track is a mechanism the FDA uses to speed up its review process. Deflazacort is a drug that is approved in a few countries outside the U.S. It’s similar to prednisone, which is widely used to treat DMD, but some believe Deflazacort’s side effects are less severe than those associated with prednisone.

A phase 1 study to determine how deflazacort is handled by the body (“pharmacokinetics” of the drug) is open at two U.S. sites in boys with DMD who are 4–16 years old and meet study criteria. A second phase 1 study for boys with DMD who have participated in the pharmacokinetic study of deflazacort is testing the safety and tolerability of the drug.

For details about the deflazacort pharmacokinetics study, enter NCT02251600 in the search box at For details about the trial for those who have previously participated in the deflazacort pharmacokinetics study, enter NCT02295748. For more about corticosteroids, read Charting a Corticosteroid Course.

Comparing Corticosteroids

An ongoing, multinational trial to study the optimum dosing schedule of prednisone or deflazacort remains open

A large-scale study comparing two dosing schedules (“regimens”) of prednisone and one of deflazacort in boys with DMD who are 4–7 years old and meet other study criteria remains open to new participants. The trial, named Finding the Optimum Regimen for Duchenne Muscular Dystrophy (FOR-DMD), aims to find out which drug and which regimen provides the most benefit with the lowest level of side effects. It’s taking place at some 40 sites in the U.S. and elsewhere. “It’s important to determine the best corticosteroid regimen,” the investigators say, “since boys will be able to take corticosteroids along with new treatments now in development.”

For details about the FOR-DMD trial comparing regimens of prednisone and deflazacort, enter NCT01603407 in the search box at Or call study project manager Kimberly Hart at (585) 275-3767.

Extinguishing the Flame

Drug designed to suppress inflammation in DMD-affected muscles

Catabasis Pharmaceuticals, which has received MDA support for development of its experimental compound CAT-1004, says it expects to open a trial of this experimental compound in boys with DMD during the first half of 2015. CAT-1004 is designed to reduce disease-contributing inflammation in the muscles of people with DMD.

CAT-1004 recently received FDA orphan drug designation, which provides financial incentives to companies developing treatments for rare disorders. MDA awarded $120,000 to Catabasis in 2012 to develop and test CAT-1004 and a related compound.

The Heart of the Matter

Cells that give rise to heart tissue may move to testing in people with DMD

Capricor Therapeutics says it has seen encouraging results in dystrophin-deficient mice with a DMD-like disorder after they were treated with its CAP-1002 cardiac stem cells. These cells are derived from donor heart tissue. The company said the findings raise the possibility that these cells may be useful therapeutically to treat heart failure in people with DMD.

No-Cost LGMD Genetic Testing

MDA clinics to offer testing for those with weakness in proximal muscles who do not have a confirmed genetic diagnosis

Limb-girdle muscular dystrophy (LGMD) is a disorder with more than 30 genetic subtypes that results in a weakness of the muscles surrounding the shoulders and hips. These are also sometimes referred to as “proximal” muscles because they are located near the center of the body.

In the past, supportive treatments for LGMD did not differ based on subtype. More recently, clinicians have worked to consider the subtype of LGMD in monitoring and treating people because some subtypes are more likely than others to involve cardiac or respiratory muscles. In some cases, weakness of the proximal muscles is associated with a metabolic muscle disorder known as Pompe disease (acid maltase deficiency), for which disease-altering enzyme replacement therapy is available. Proper diagnosis can help people access appropriate care faster.

With support from Genzyme, a Sanofi company, and in collaboration with Emory University, MDA clinics are now offering testing for people who have weakness in proximal muscles and who do not have a confirmed genetic diagnosis. Based on testing of a saliva sample collected at an MDA clinic and sent to the Emory Genetics Laboratory, the results are returned to physicians and communicated to participants within two to three months.

For more information about testing related to weakness in proximal muscles, please speak with your MDA health care service coordinator or clinic physician. To learn more about LGMD and its many forms, read In Focus: Limb-Girdle Muscular Dystrophy, which includes a helpful Q&A with genetic counselor Christina Trout.

Aiming Antisense at MMD

Testing underway for drug targeting the underlying molecular defect in MMD1

A phase 1-2 trial of ISIS-DMPKRx, an experimental compound for the treatment of type 1 myotonic muscular dystrophy (MMD1 or DM1), is now underway in the U.S. in adults with this disorder who are 20–55 years old and meet other study criteria. Isis Pharmaceuticals, which is developing the drug in collaboration with Biogen Idec, announced the opening of the new trial in December 2014.

MDA supported much of the foundational research that led to understanding this phenomenon and developing antisense-based strategies to counteract its effects.

The phase 1–2 trial of ISIS-DMPKRx will enroll approximately 36 adults with MMD1 at seven U.S. sites. Participants will be randomly assigned to receive injections of the drug under the skin or a placebo for six weeks. They will receive multiple injections of the drug at a specific dose, with different groups receiving different doses, to help establish the safety and tolerability of ISIS-DMPKRx.

For details of the ISIS-DMPKRx study, enter NCT02312011 in the search box at You also can contact Isis Pharmaceuticals at (800) 679-4747 or For more about antisense and related strategies to treat myotonic dystrophy, read MMD Research: Seeking to Free Proteins from a ‘Toxic Web' at

Olesoxime Moving Forward

Roche developing compound designed to protect SMA-stressed mitochondria

Swiss pharmaceutical company Roche announced in February that it will acquire French biotechnology company Trophos, which has been developing the drug olesoxime as a potential treatment for spinal muscular atrophy (SMA). The experimental compound, also known as TRO19622, is designed to preserve the structure and function of the energy-producing parts of cells known as mitochondria, despite the presence of adverse conditions like SMA.In April 2014, Trophos announced that a two-year study of olesoxime compared to a placebo in patients with type 2 or 3 SMA showed those treated with the drug maintained motor function, while those treated with the placebo did not.

“We will build on the work done by Trophos and the French Muscular Dystrophy Association to advance the development of olesoxime and to bring it to people who live with this devastating condition as quickly as possible,” said Sandra Horning, chief medical officer and head of global product development at Roche.

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