Progress Now Summer 2015

Research and clinical trial updates

by Quest Staff on July 14, 2015 - 3:03pm

Quest Summer 2015

MDA welcomes a neurological disease expert to the family

Lianna Orlando

As part of its continued work to enhance its research and clinical and family support programs, MDA has hired Scientific Program Officer Lianna R. Orlando, Ph.D. Orlando comes to MDA from Fidelity Biosciences Research Initiative, where, as associate director, she oversaw funding of research projects in neurodegenerative diseases, such as Alzheimer’s disease, and organized and hosted scientific conferences. Prior to her time at Fidelity, she was a junior faculty member at Massachusetts General Hospital, where her work focused on glutamate receptors and neurodegeneration. While Orlando completed her doctoral studies at Harvard University, she also earned an additional master’s in medicine from Harvard Medical School in order to better understand human pathophysiology and more effectively translate findings from basic scientific research to the treatment of human disease. 

Orlando will provide leadership for MDA through interactions with federal agencies, international neuromuscular disease partners, philanthropists, investors, drug development groups and biopharmaceutical companies, as well as with patient advocacy groups and other neuromuscular disease stakeholders. Her concentration on MDA’s research team will be managing the grant portfolios for muscle diseases including myotonic dystrophy, congenital myopathies and mitochondrial myopathies.

“I am thrilled to join MDA at such an exciting time, when research is taking center stage,” Orlando says. “MDA has had a hand in nearly every neuromuscular disease research breakthrough, and I look forward to applying my experience supporting research efforts in other areas to help MDA continue to achieve its mission.”     

Orlando joins recently hired Scientific Program Officers Amanda Haidet-Phillips, Ph.D., and Laura Hagerty, Ph.D. All three will work alongside MDA Senior Vice President and Scientific Program Director Grace Pavlath, Ph.D., and together will lead MDA as it accelerates new front-line discovery in search of treatments and cures for muscular dystrophy, ALS and other life-threatening diseases that limit strength and mobility.

“As we continue to build a powerful research team here at MDA, we are lucky to have Lianna be a part of it. She brings an incredible amount of expertise to the field of research development in the neurological space,” says Valerie A. Cwik, M.D., MDA’s executive vice president and chief medical and scientific officer. “MDA remains committed to pursuing lifesaving discoveries, and I’m looking forward to working with Lianna and the team to ensure that MDA continues to prioritize progress for the families we serve and the larger research community.”

MDA has an aggressive plan in place to significantly increase and refocus its research investments; forge new partnerships with biopharmaceutical companies and others; facilitate more clinical trials; improve the quality of care, services and therapies for families; and open new channels to connect with people who need MDA’s assistance. Currently, MDA is funding about 250 research projects in 16 countries. It also operates a network of more than 150 clinics nationwide, assisting more than 100,000 individuals registered with MDA. 

Co-funded MDA and AANEM grants seek to support new investigators and accelerate research

All MDA grants have the same basic goal: moving promising treatments through the drug development pipeline, from early discoveries in the lab, to clinical trials, to actual therapies that can be prescribed in the clinic. But some MDA grants are designed to accomplish this goal not only by funding research itself but also by encouraging the best and brightest young scientists to become future neuromuscular disease researchers. 

Now MDA and the American Association of Neuromuscular & Electrodiagnostic Medicine Foundation for Research and Education (AANEM) have partnered to fund neuromuscular disease research — with the goal of helping young researchers establish themselves and commit to the neuromuscular disease field.

The partnership allows both groups to leverage donor dollars to advance key research objectives.

“We are very excited to work with the AANEM Foundation,” says MDA Executive Vice President & Chief Medical and Scientific Officer Valerie A. Cwik, M.D. “There are many important research projects in need of funding, and this collaboration will allow us to expand opportunities to accelerate the search for treatments and cures.”

Read Seeding the Field for more on MDA’s efforts to encourage young scientists to become future neuromuscular disease researchers.

Stanford University collecting research tissue samples from families with neuromuscular disorders 

Ever wonder how someone with a neuromuscular disorder in his or her family might contribute to research efforts in that field? One very powerful way is to donate samples to a tissue bank, such as the Stanford Neuromuscular Biobank at Stanford University. 

The Stanford Biobank collects and organizes samples of blood, muscle, skin, spinal fluid and other tissues from people with neuromuscular disorders and their unaffected family members. Samples can be collected with the patient’s consent during routine clinic visits, during scheduled surgical procedures or after death with the family’s consent. The Biobank stores these samples so that they can be shared with researchers seeking to understand how neuromuscular conditions affect the body and what might be the most meaningful treatments. 

The Biobank is overseen by John Day, a physician-scientist who specializes in neuromuscular disorders. Day has received MDA research funding and directs the MDA Neuromuscular Disease Clinic at Stanford.

Researchers do not receive any personal identifying information about the donor. The Biobank takes care of all arrangements and any associated costs.

For more information, see You also can request information by emailing or calling (650) 497-9807.

Allied Against ALS 

MDA joins forces with a group of other organizations to fight the disease

MDA is pleased to announce its involvement in the first-ever ALS Collaboration for a Cure — a group of nearly 20 organizations dedicated to fighting ALS (amyotrophic lateral sclerosis) that are uniting this year to accelerate progress. 

Together with the ALS Association, ALS Therapy Development Institute (ALS TDI), and numerous other ALS organizations and partners, MDA is joining forces to revolutionize the fight against this debilitating disease. The first three areas of focus include:

  • elevating the national ALS registry so scientists can better understand and treat the disease;
  • bringing new therapies to families more easily and efficiently by developing a guidance document to help companies and researchers involved in ALS drug development navigate the regulatory process and speed drug development; and
  • improving access to, and communications about, treatments in development that show potential to fight this devastating disease. 

Representatives from participating organizations will work together to follow up on and drive progress for everyone fighting ALS.

People with ALS and/or their caregivers are encouraged to register at, where they will be asked to fill out short surveys about their and their families’ health, their military background and their environmental and occupational exposures. And be sure to check out MDA’s ALS disease information center

Faulty Disposal System

Defects in cellular ‘garbage-clearing’ pathway could be at fault for some forms of ALS

The gene for a protein called TBK1 can, when flawed, lead to ALS, adding to the approximately 30 genes that have been linked to the disease so far. The ALS-causing flaws (mutations) identified by Axel Freischmidt at Ulm University in Germany, and colleagues, appear to reduce the function of TBK1, a protein that normally helps break down defective cellular proteins in a cellular cleanup and disposal pathway known as “autophagy.”

The identification of genes associated with ALS may suggest biological targets at which to aim potential therapies. The authors say the findings emphasize the importance of TBK1, and possibly autophagy, in maintaining the health of nerve cells over a lifetime. To learn more, read the full study results

Getting Back Into Shape

A strategy to help proteins fold normally could help treat SOD1-related ALS

It’s been known since the early 1990s that mutations in the gene for the SOD1 protein can cause human ALS, as well as an ALS-like disorder in mice. Mutations in the SOD1 gene cause the SOD1 protein to fold into abnormal shapes, making it toxic to nerve cells. Now, scientists funded in part by MDA have shown that a protein called MIF can act as a “chaperone” for the SOD1 protein, counteracting the misfolding that occurs with this protein in ALS, thereby reducing the damage it does to cells. 

MDA research grantee Adrian Israelson at Ben-Gurion University of the Negev in Beer Sheva, Israel, and colleagues, note that, “Identification of MIF as an intracellular chaperone that stimulates folding/refolding of misfolded SOD1 suggests a new avenue for therapy development in ALS.” To learn more, read the full report (paywall). 

Viral Triggers

Abnormalities in senataxin gene lead to excessive response to viral infection, may cause ALS

Back in 2004, an international research group supported in part by MDA found that flaws in the gene for the senataxin protein could cause a slowly progressive juvenile-onset form of ALS. However, the normal functions of the senataxin protein were barely understood. Now, Matthew Miller at McMaster University in Hamilton, Ontario, Canada, and colleagues, have found that the senataxin protein normally plays a role in controlling the body’s response to viral infection, helping to ensure that the response is appropriate and not so extreme that it could be harmful. 

Abnormalities in senataxin could, the evidence suggests, result in an excessive response to a viral infection and, over time, progressive deterioration of tissues. The findings also suggest a possible link between viral infections and senataxin-linked ALS and support the idea that infection has an important role in the initiation or progression of this juvenile-onset form of ALS. To learn more, read the full study results.

Getting Closer

Two exon-skipping drugs move closer to U.S. market availability

Two experimental drugs in development for the treatment of Duchenne muscular dystrophy (DMD) are moving forward in the regulatory approval process.

BioMarin Pharmaceutical announced April 27, 2015, that it has completed the rolling submission of a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for its investigational drug drisapersen for the treatment of DMD. Sarepta Therapeutics then announced May 19 that it has begun submission of a rolling NDA for its investigational drug eteplirsen and plans to complete the submission by mid-year.

The loss of a protein called dystrophin is the underlying cause of DMD, which causes progressive loss of muscle strength and severe weakening of respiratory and cardiac muscle. Both drisapersen and eteplirsen are “exon-skipping” drugs, designed to target and block a section of the dystrophin gene known as exon 51. In people with mutations near (but not in) dystrophin exon 51 — about 13 percent of DMD patients — these drugs may allow production of functional dystrophin protein.

“This is very encouraging news for the DMD community,” says MDA Scientific Program Officer Laura Hagerty, Ph.D. “MDA has supported research in exon skipping for DMD since the 1990s, and we are more committed than ever to bringing safe and effective treatments and cures to kids and adults living with neuromuscular diseases as quickly as possible.”

Breathe Easier 

Phase 3 trial in DMD suggests idebenone preserves respiratory function

Santhera Pharmaceuticals published results April 21, 2015, from a yearlong phase 3 clinical trial, indicating that the experimental drug idebenone slows the decline of respiratory function in people who have DMD.  

In the trial, people with DMD ages 10–18 years old received either treatment with idebenone (currently marketed for other disorders under the brand names Raxone and Catena) or a placebo for a period of one year. Results demonstrate that idebenone was safe and well-tolerated. In addition:

  • Treatment with the drug significantly reduced the decline in an important respiratory measurement called Peak Expiratory Flow.
  • Positive effects on several other measures of respiratory function were noted. 

Study investigators note idebenone may represent a new treatment option for people with DMD. In slowing the rate of decline in respiratory function, the drug may decrease the need for ventilator assistance and result in improved quality of life.

Idebenone has been granted orphan drug designation for DMD in Europe and the U.S. The FDA recently granted it Fast Track designation, which hastens the review process through which it may be approved as a treatment for DMD.

To read the full trial results, search for “NCT01027884” at Clinical For additional information on idebenone trials in DMD, read DMD: Idebenone Slows Decline of Respiratory Function.

Adding Eplerenone

The drug, which increases water excretion, may inhibit heart muscle degeneration in DMD

Investigators at three U.S. centers studied 42 boys with DMD who were at least 7 years old, had signs of cardiac damage and were being treated with heart medications (specifically, angiotensin converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs)). Study participants were randomly assigned to continue receiving their current heart medications plus the drug eplerenone, or their current heart medications plus a placebo. Eplerenone increases water excretion. After a year, those in the eplerenone group showed a slower decline in heart function than those who received the placebo.

Subha Raman and colleagues said that use of drugs like eplerenone in DMD might be worth considering early in the disease course but that further studies are needed. For more details, search “NCT01521546” at

Rituximab Trial Recruiting

Drug aims to reduce or eliminate need for prednisone and its unwanted side effects

A trial of the immunosuppressant rituximab remains open to participants who have myasthenia gravis (MG), are 21–90 years old, are on prednisone and meet other study criteria. The phase 2 trial will help determine whether rituximab, an intravenous medication that targets specific cells in the immune system, can help patients reduce or eliminate their prednisone dosage, which though effective can cause serious side effects. 

Promising results could lead to further study of the experimental drug in a phase 3 efficacy trial. For details about the rituximab trial, search “NCT02110706” at

Cabaletta Fast-Tracked

The FDA designation hastens the regulatory review process

BioBlast Pharma announced April 9, 2015, that the FDA has granted Fast Track designation for its investigational drug Cabaletta for the treatment of oculopharyngeal muscular dystrophy (OPMD)

The Fast Track designation hastens the review process through which the FDA may approve Cabaletta as a treatment for OPMD. 

“OPMD is a rare and debilitating muscular dystrophy for which there is currently no cure or approved drug therapy, so this is particularly encouraging news,” notes MDA Senior Vice President and Scientific Program Director Grace Pavlath, Ph.D.

BioBlast currently is conducting a phase 2-3 clinical study for OPMD at trial sites in Jerusalem and Montreal. An additional trial site has opened in Los Angeles but is not yet recruiting. 

For more information on Cabaletta, check out Taking Aim at Protein Clumps, or search “NCT02015481” at

A Preventive Measure

New trial seeks to prevent disease progression in presymptomatic infants with genetic diagnosis of SMA

Biogen Idec plans to run a phase 2 clinical study of the experimental drug ISIS-SMNRx in infants with spinal muscular atrophy (SMA) who are less than 6 weeks old and have a genetic diagnosis of the disorder but are not yet showing symptoms. 

ISIS-SMNRx is being developed by Isis Pharmaceuticals in collaboration with Biogen Idec. Developed using a gene-modifying strategy known as antisense, it targets the SMN2 gene and encourages production of the full-length SMN protein that is needed but deficient in SMA-affected cells. It is hoped that administering this drug very early in life may prevent the development of SMA-associated weakness. MDA-funded laboratory research contributed to the development of ISIS-SMNRx.

The new phase 2 exploratory clinical study — dubbed NURTURE — is being conducted in presymptomatic infants with a genetic SMA diagnosis to see whether early treatment with ISIS-SMNRx, before signs of SMA are evident, could delay or even prevent the development of the disease, as well as to further investigate the safety and tolerability of the drug. The trial is expected to include up to 25 infants from around the world, with participating sites at centers in the U.S., Taiwan and other countries.

ISIS-SMNRx is also being tested in ongoing, open phase 3 trials in infants with SMA who are up to 7 months old and showing symptoms (ENDEAR), and in children with SMA who are 2–12 years old (CHERISH).

For details and contact information for these studies, visit — search “NCT02386553” for the presymptomatic infant study of ISIS-SMNRx (NURTURE); search “NCT02193074” for the symptomatic infant trial (ENDEAR); and search “NCT02292537” for the trial in children ages 2–12 (CHERISH). 

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