Parent Project Muscular Dystrophy: Advocacy and Support

The diagnosis of Duchenne muscular dystrophy (DMD) is devastating for patients and their families. There is no standardized treatment and no cure, and boys with this disorder typically die by age 25 years because of respiratory failure or failure of the heart muscle. Until 13 years ago, parents of boys with DMD had nowhere to turn for support and no concerted efforts in clinical research were being made. This changed in 1994 with the founding of Parent Project Muscular Dystrophy (PPMD), a grassroots organization started by parents with the goal of creating awareness of DMD and generating interest and funding for research.

Since its inception, PPMD has grown from being a support and advocacy group to an organization that provides various services for parents and children with DMD. Services include an annual meeting, education, a quarterly newsletter, and a comprehensive Web site (www.parentprojectmd.org). The group also has formed partnerships with industry to encourage drug development and research funding.

GENESIS OF PPMD
DMD is the most prevalent form of muscular dystrophy, affecting about 1 in 3500 male newborns.¹ It is one of the most lethal genetic disorders diagnosed during childhood. Pat Furlong, director and founder of PPMD, knows firsthand about the disease and its aftermath. The genesis of the parent-centered organization was spurred by her frustration in finding support resources for her 2 sons. Both had DMD and died at ages 15 and 17.

When DMD was diagnosed in her children in 1984, Furlong began traveling to clinics across the United States to learn more about standards of care and ongoing research for this disease. "I kept coming up against a wall," she said. "There was no money and no federal investment in research. Doctors told me there was nothing they could do for my sons and that they would ultimately die in adolescence of the disease." Furlong refused to accept this prophecy and was galvanized into action.

Even though the gene for DMD and the virus that triggers its expression were identified in 1986, no treatments were developed over the next several years. Furlong was amazed and disgruntled by the lack of communication about DMD. Scientists were not talking to clinicians and clinicians were not talking to patients and families. She believed that parents of patients should mobilize and lobby for research on DMD. Thus, the PPMD was formed.

INAUGURAL MEETING
For the first meeting of PPMD, Furlong cajoled French Anderson, a Nobel Prize winner for genetic discoveries, to attend, thinking he would be a drawing card. "He stirred the pot and introduced the idea of viral gene therapy. He started the crosstalk and made people think about creating centers of excellence to concentrate on DMD," she said.

By 1995, the University of Pittsburgh Medical Center in Pennsylvania had a critical mass of patients with DMD. This facility became the first center of excellence, providing imaging and research on basic science and the feasibility of adult-derived stem cell treatment for DMD. Two core laboratories for animal research were doing complementary studies-one at the University of Buffalo and the other at the University of Missouri. The University of California at Los Angeles soon became a second center of excellence, focusing on the inflammatory component of DMD.

"These centers of excellence served as catalysts for research funding," Furlong explained.

ADVOCACY EFFORTS
The community of PPMD members began advocacy efforts in earnest, writing letters to Congressmen and hiring lobbyists in Washington. As a result, the federal government passed the Muscular Dystrophy Community Assistance, Research, and Education Amendments (MD CARE) Act in 2001, calling for centers of excellence and a surveillance program for persons with muscular dystrophy. This law led to an infusion of new funding and the establishment of 6 research centers of excellence, and a surveillance program through the CDC, with the goal of creating a registry of boys with DMD. A Muscular Dystrophy Coordinating Committee was formed based on recommendations from the Department of Health and Human Services; the committee had a mandate to design and implement a research and care plan.

In addition to advocacy efforts, PPMD provides a virtual community for parents of boys with DMD. "This is a devastating and rare disorder, and for at least 40% of boys, there is no family history of the disorder," Furlong said. "The diagnosis hits you like a ton of bricks. Parents of these children need support."

Currently, there is no standard of care for DMD, but PPMD is working with Cincinnati Children's Hospital Medical Center to develop a standard of care that will help boys live longer, walk better, and have an improved quality of life. PPMD, in collaboration with the Cincinnati Children's Hospital, has developed an evidence-based DVD on the care and management of DMD, which has been approved by the CDC.

EDUCATION
PPMD's Web site, www.parentprojectmd.org, presents breaking news and information on research, treatment, care, emotional and educational issues, advocacy, and resources.

PPMD has developed additional educational materials for parents and other laypersons. A short animated video called "BrainPOP" sensitizes viewers about what to expect in boys with the disorder and explains the diagnosis. PPMD also publishes a free quarterly newsletter for parents, which presents updates of ongoing programs and information about new PPMD initiatives.

Physician education takes the form of workshops on topics such as preserving bone density, cardiac protection, treatment, and behavioral issues. The Annual Meeting of PPMD is a gathering point for scientists, clinicians, parents, and affected young adults. Presentations at the meeting are focused on state-of-the-art treatments, clinical trials, and research. This year for the first time, the meeting will feature a panel discussion with young adults with DMD. PPMD is also pursuing CME accreditation for the meeting to encourage clinicians and health care professionals to gain expertise about care and research.

"Trying to create programs where we can offer the highest quality clinical care is a challenging and exciting opportunity," said Giovanna M. Spinella, MD, who recently took on the role as PPMD's first medical director. "I think we can raise the bar on the care, health, and quality of life for boys with DMD," she said. Spinella, a pediatric neurologist at the NIH who previously worked as a staff neurologist at Walter Reed Army Medical Center, explained that care for boys with DMD is currently irregular and inconsistent. A standardized approach is needed to ensure that data on the benefits of treatment are accurate. Once a standard of care is developed, the medical community will be better able to identify effective treatments.

INDUSTRY COLLABORATION
PPMD is pursuing relationships with industry in hopes of moving basic science to treatment development. The group established Project Catalyst in 2003, a research initiative with PTC Therapeutics, a company dedicated to the development of small-molecule drugs for genetic disorders as well as for oncological and infectious diseases. The goal is to identify and characterize compounds that modulate expression of 5 target proteins. In 2005, PTC Therapeutics and PPMD moved into the second part of Project Catalyst's Lead Optimization, with the goal of improving compound efficiency, minimizing toxicity, and fine-tuning pharmacological properties.

"It is believed that DMD in approximately 15% of affected boys is caused by a nonsense mutation in the dystrophin gene," explained Furlong. "PTC 124 is a novel drug that allows the cellular machinery to bypass the nonsense mutation and continue the translation process, restoring the production of full-length, functional protein. Phase 2 clinical trials are currently under way," she added. "Preliminary results have been encouraging.

"This is the first time that an oral medication has been shown to restore dystrophin production in boys with DMD," Furlong continued. "We now have our first glimpse that DMD can and will be treated."

GLOBAL INITIATIVE
Because DMD is such a rare disease, collaborating with advocacy organizations in other countries can spur research efforts by enlarging the pool of patients. In January, 4 of the world's leading muscular dystrophy organizations-PPMD, Association Francaise Contre Les Myopathies (AFM), the Muscular Dystrophy Association, and the Netherlands advocacy group United Parent Project Muscular Dystrophy-met to form a coalition to pool knowledge and resources to jump-start development of promising treatments and perhaps even a cure for DMD. Together, they launched the Duchenne Research Collaborative International (DRCI).

DRCI members will support projects to accelerate translational research into therapeutic options to treat DMD, explained Lou Kunkel, PhD, professor of genetics and pediatrics at Harvard Medical School in Boston. Kunkel is head of the team that identified the gene for DMD in 1986.

The DRCI has 3 immediate goals: (1) to develop a clearinghouse for research investments and research resources for the international community; (2) to form a global patient registry that will serve as a super database for researchers, giving patients the opportunity to be selected for clinical trials that are potentially lifesaving; and (3) to create a global clinical trial network, bringing translational research to the clinical setting, thus avoiding duplication of effort by different countries.

The president of the AFM, Laurent Tiennot-Herment, said that the DRCI represents a significant step forward for the DMD community and provides a model for other rare diseases. "We are confident that the framework we are putting into place can be widely replicated for the benefit of patients with other neuromuscular conditions all over the world," he said.

The DRCI has several challenges to address, including development of better animal models for DMD, establishment of improved evidence-based standards of care, greater engagement of industry partners, and reduction in fragmentation of research.

REFERENCE1. Van Essen AJ, Kneppers ALJ, van der Hout AH, et al. The clinical and molecular genetic approach to Duchenne muscular dystrophy: an updated protocol. J Med Genet. 1997;34:805-812.