WHAT DISEASE IS MDA STRIVING TO DEFEAT

What Does MDA Do?
MDA works in Wisconsin to combat neuromuscular diseases through:
(1) basic and applied scientific investigation,
(2) local comprehensive programs of medical services and clinical care
(3) widespread professional and public health education. 

Thanks to the MDA Labor Day Telethon, brought to you and thousands of other viewers by a “Love Network” TV station, and many other local fund-raising projects involving all sectors of the community, MDA has been able to organize and maintain a variety of programs and services.

MDA-supported research marked rapid and significant progress on a number of fronts in 2005-2006. Here are some of the highlights.

In a major milestone in the history of MDA research, the U.S. Food and Drug Administration approved the marketing of Myozyme, the first definitive treatment for a genetic neuromuscular disease in MDA's program. Myozyme, an enzyme replacement therapy, has been tested in infants and young children born with Pompe's disease (acid maltase deficiency). These children, without Myozyme, faced a life expectancy of about two years; with the treatment, their strength and life expectancy were significantly extended.

MDA supported early-stage research that led to the development of Myozyme, and partnered with biotech company Genzyme during the clinical phases of development. The partnership continues to evolve as the drug is tested in those with late-onset Pompe's.

MDA launched two programs in amyotrophic lateral sclerosis (ALS) research: Map ALS, an intense all-out effort to uncover molecular changes associated with ALS and identify compounds that may affect those changes; and the ALS translational research program, to fast-track promising findings into human clinical trials.

In addition, researchers have identified a genetic "missing link" that supports the theory that ALS is caused by both genetic predisposition and environmental toxins.

Gene therapy also took an historic step in Duchenne muscular dystrophy (DMD) research. Several other diseases under MDA's umbrella saw research advances or explorations of potential drug therapies.

Duchenne Muscular Dystrophy
March 28, 2006, marked the start of the first U.S. human gene therapy trial in DMD, made possible by incremental advances over years of MDA-funded research. The trial at Columbus (Ohio) Children's Hospital, to include six boys with DMD, tests the safety of Biostrophin, developed with an MDA grant by Asklepios Biopharmaceutical of Chapel Hill, N.C. Biostrophin delivers miniaturized functional dystrophin genes in viral carrier shells to muscle cells. The dystrophin protein is missing in DMD.

A new "two-gene" technique developed by MDA grantees at Stanford University significantly boosted production and distribution of dystrophin in mice. The technique inserts a "naked" corrected dystrophin gene without a virus carrier shell, and a second gene that coaxes new genes to integrate into an existing chromosome. Dystrophin production in mice muscles was eight times higher than that yielded by using dystrophin genes alone.

The potential for a DMD treatment at the genetic level also is being pursued at PTC Therapeutics of South Plainfield, N.J., with the help of an MDA grant. The company has moved to phase 2 clinical trials of the drug PTC124, which permits cells to "read through" muscle cell genetic errors found in about 15 percent of children with DMD.

MDA grantees at Carolinas Medical Center in Charlotte, N.C., and the University of Western Australia in Perth, were on a team that achieved encouraging results using a strategy known as exon skipping to repair mutated dystrophin genes in mice with a disease resembling Duchenne MD. The strategy causes cells to remove (skip) the mutation in the dystrophin gene and splice together surrounding genetic instructions. It can be targeted toward several types of mutations seen in DMD.

Three university-affiliated labs, all supported by MDA, reported success creating miniaturized dystrophin genes that improve muscle function and life span in mice with a disease resembling DMD. Miniaturization of the very large dystrophin gene is necessary for gene therapy strategies. Knowing which parts of the gene can be left out is crucial for the development of treatments that involve skipping over genetic mutations.

ALS
Two research teams, each with strong MDA connections, have independently verified a link between sporadic ALS and certain variations in genes for paraoxonase enzymes (PONs). PON enzymes handle toxins like pesticides, nerve gas and anti-nerve gas medications. Sporadic ALS, which occurs with no known family history, affects some 90 percent of those with the disease.

Identifying genetic targets for drug intervention is the goal of MDA's new program, Map ALS, which seeks to move forward in record time by pooling talent, technology and money.

As one of the first projects, the nonprofit Translational Genomics Research Institute (TGen) in Phoenix received an MDA grant to identify differences in the genes of people with and without ALS, in hopes of unlocking secrets to early ALS diagnosis and providing new targets for drug development.

MDA research grantees at Massachusetts General Hospital in Boston were part of a group that identified possible biological indicators of ALS in spinal fluid. These "biomarkers" are useful for diagnosis and as indicators of treatment efficacy.

MDA grantees at Wayne State University in Detroit and the University of Wisconsin-Madison reported increased life span and motor function in ALS-affected mice after injecting "naked" insulinlike growth factor 1 (IGF1) genes under pressure. The strategy makes it possible to deliver genes without using viruses, which improves patient safety.

A clinical trial of the compound arimoclomol began under the auspices of the biotech firm CytRx and the MDA/ALS Center at SUNY Upstate Medical University in Syracuse, N.Y. Arimoclomol helps cells survive under stress and may prevent abnormal protein clumping.

A compound dubbed GPI-1046, developed with MDA support at Johns Hopkins University in Baltimore, increases removal and recycling of the central nervous system chemical glutamate in mice. Glutamate has been implicated in nerve cell death in ALS.

A clinical trial of ceftriaxone, an antibiotic approved to treat certain types of infection, and also found to increase glutamate recycling, began at multiple MDA clinic sites in the summer of 2006.

Mouse embryonic stem cells were coaxed into becoming functional motor neurons in the spinal cords of paralyzed rats, a success that could one day lead to treatments for ALS and spinal muscular atrophy, as well as spinal cord injuries. An MDA-supported research team reports their four-step process restored functional nerve-to-muscle connections and movement in the back legs of rats paralyzed by a virus.

A large-scale MDA-funded study of genetics and disease patterns in ALS entered phase 2 at the Eleanor and Lou Gehrig MDA/ALS Center at Columbia University Medical Center in New York. The study seeks relationships between ALS and genetic makeup or environmental exposures.

MDA funded the online national ALS registry, ALS Connection (www.alsconnection.com), coordinated by the Forbes Norris MDA/ALS Center at California Pacific Medical Center in San Francisco. The registry gathers data useful in determining risk factors for ALS, as well as beneficial interventions and educational strategies.

Other Research Progress
An MDA grantee at the University of Massachusetts Medical School at Worcester has uncovered more pieces of the puzzle of facioscapulohumeral muscular dystrophy (FSHD), by determining that mice developed to overproduce a protein called FRG1 display severe muscle symptoms closely resembling those of FSHD. The hypothesis is that the genetic mutation known to cause FSHD in humans does so in part by increasing FRG1 production.

In the fight against spinal muscular atrophy (SMA), an MDA grantee at Stanford University was part of a research team demonstrating that the drug hydroxyurea increased the production of full-length SMN, the vital protein deficient in SMA. Also, an MDA grantee at the University of Missouri at Columbia found that drugs in the aminoglycoside family put a molecular "tail" on shortened SMN proteins produced by flawed cells, yielding more normal full-length SMN molecules.

The well-established drug valproate, used for seizure control, migraines and bipolar disease, significantly increased strength in six people with type 3 or 4 (relatively mild) SMA, according to a pilot study by a team that included an MDA grantee at the University of Washington School of Medicine in St. Louis. A larger trial that includes more severely affected patients is under way.

The protein erythropietin, known to boost red blood cell production, also increases levels of the protein frataxin, which is deficient in people with Friedreich's ataxia. This finding by a team led by an MDA grantee at the Medical University of Vienna (Austria) may provide a direction for future drug development in Friedreich's.

In research on sarcoglycan-deficient limb-girdle muscular dystrophy, MDA grantees at the University of Pittsburgh were on a team that successfully transferred genes for delta-sarcoglycan to hamsters. The gene transfer significantly improved the hamsters' cardiac and whole-body functioning, and extended their lives.

MDA clinic directors from across the United States attended a conference called Translating Basic Research Knowledge into Clinical Strategies at MDA headquarters in Tucson in November. The three-day conference updated participants on trends in the diagnosis and medical management of neuromuscular diseases.

Three new muscular dystrophy Centers of Excellence were created this year in Washington, D.C., Philadelphia and Iowa City, Iowa, as part of the MD-CARE Act passed by Congress in 2001 with support from MDA.

MDA sponsored a seminal meeting in Washington on challenges in drug development for muscular dystrophy. Representatives of the Food and Drug Administration, the National Institutes of Health, academic institutions and eight for-profit companies participated.

Health Care and Community Services

MDA's medical and support services provided a lifeline to individuals and families across the United States and Puerto Rico who are affected by neuromuscular disease.

The Association opened new MDA/ALS centers in Oklahoma City, Portland, Ore., and Memphis, Tenn. The 37 MDA/ALS Centers feature highly focused programs of ALS research and medical management and a multidisciplinary approach to care.

Tens of thousands of individuals with muscle-wasting diseases received diagnostic and follow-up medical care through MDA's national network of 235 hospital-affiliated clinics. Staffed by neuromuscular disease experts, the clinics also offer assessments for several types of therapy, genetic counseling and referrals to other specialists.

MDA provided financial support for the purchase of nearly 3,400 wheelchairs and leg braces and hundreds of communication devices, and paid for more than 5,300 repairs to wheelchairs and leg braces.

MDA loan closets had a record year, increasing their distributions by 15 percent, thanks to increased public awareness that MDA accepts donations of used equipment. The closets were able to give out some 5,000 pieces of durable medical equipment such as lifts, walkers and hospital beds.

MDA's health care services program also offered emotional support, through some 290 professionally facilitated support groups helping families better cope with challenges, and through local educational seminars and workshops providing the latest information on living with muscle disease.

Help is only a call away thanks to MDA's toll-free lifeline, (800) 572-1717, which automatically routes callers to the MDA offices serving their areas. The lifeline handled 28,555 calls in fiscal 2006, providing referrals, services, information and support.

MDA summer camp worked its magic at 90 camp sessions at 78 locations last summer, at no cost to campers' families. In addition to enjoying physical activities geared to their interests and abilities, more than 4,200 campers ages 6 to 21 made arts and crafts, friends and memories at wheelchair-accessible camps across the country. Campers were assisted and cared for by some 5,000 volunteers (319 serving as medical staff) who selflessly gave of their time and talent.

Professional and Public Health Information

As part of its mission, MDA provides information in a wide variety of formats for individuals and families affected by neuromuscular disease, caregivers, health care and medical professionals, researchers and the general public.

Publications

MDA's booklet for parents, "Learning to Live with Neuromuscular Disease," was updated and revised, in order to help families better cope with the impact of a child's neuromuscular disease on their lives. The revised booklet contains expanded information and resources, as well as photos of and quotations from families served by MDA and children's artwork from the MDA Art Collection.

In addition, "A Teacher's Guide to Duchenne Muscular Dystrophy" was expanded and revised to become "A Teacher's Guide to Neuromuscular Disease." The revised booklet provides teachers with up-to-date medical information about all the muscle diseases that affect children, educational strategies, suggestions for accommodation and inclusion, resources and answers to such delicate questions as "What should I say to other students about the neuromuscular disease?"

These and other MDA publications are offered in both English and Spanish.

Several MDA publications earned awards in national media competitions. Issues of the bimonthly magazine Quest and the monthly MDA/ALS Newsmagazine, and "A Teacher's Guide to Neuromuscular Diseases," were honored in the Communicator Awards competition. In addition, Everyday Life With ALS: A Practical Guide, a book-length project released in 2005, was recognized by the Society of National Association Publications and the APEX Awards for Publication Excellence from Communications Concepts.

Web Sites
MDA's primary Web site changed its address from http://www.mdausa.org/  to http://www.mda.org/  during fiscal 2006. Approximately 5.5 million visits were logged from people seeking information about MDA programs and online access to MDA's many publications. The site provides up-to-date information on research findings and clinical trials relevant to people with any of the neuromuscular diseases in MDA's program.

The site also drew hundreds of chatters to dozens of regularly scheduled, hosted chats for those with specific neuromuscular diseases, as well as for caregivers, teens, young adults and others. Special pages provided the media with access to PSAs, photos, press releases and fact sheets. Donors were able to give through the site's "quick click" feature.

MDA continues to host specialized Web sites for people with ALS (www.als-mda.org) and people who speak Spanish (www.mdaenespanol.org).

An intensive Web site redesign was undertaken and launched in 2006. The redesign improved the site's accessibility by making all information available in fewer mouse clicks.

Media
Public service announcements (PSAs) about neuromuscular diseases and the Association's programs were carried by a large number of newspapers, magazines and television stations. The MDA message also was broadcast through news, feature stories and opinion pieces in local and national media, including "Live with Regis and Kelly," "The Today Show," "Larry King Live," "NBC Nightly News," CNN, Fox News, the Los Angeles Times and Parade magazine. Public service announcements featuring Jerry Lewis and National Goodwill Ambassador Luke Christie were distributed nationwide.

MDA's Television Production Division produced informational and motivational materials for the general public, health professionals and the 2005 Telethon. The department's productions were honored with five awards in the prestigious 2005 Telly Awards, which recognizes outstanding video and film production.

In fiscal 2006, MDA produced a 30-minute television special titled "Play After Every Storm: Remembering Mattie Stepanek," a tribute to the poet, peacemaker and MDA National Goodwill Ambassador who died in 2004. The special, which was hosted by MDA Telethon co-host Jann Carl and featured Mattie's mother, Jeni Stepanek, was broadcast nationally by more than 100 stations.

Key Volunteer Leaders
Early in 2006, MDA National Chairman Jerry Lewis was featured alongside National Goodwill Ambassador Luke Christie in an MDA-produced television public service announcement campaign titled "Luke's Dreams," which also was disseminated in versions for radio and print media.

MDA continued to focus public awareness on the fight against neuromuscular diseases through the efforts of volunteer ambassadors, National Task Force on Public Awareness members and Personal Achievement Award recipients.

The 12 members of the National Task Force on Public Awareness are valuable volunteer consultants for the Association, particularly on issues of interest to people with disabilities. These adults affected by neuromuscular diseases are leaders in their communities and professionals in many fields such as law, education, communications, engineering and computer technology.

Twins Kelly Buonaccorsi and Kristen Connors of Cranston, R.I., 34, received MDA's 2006 National Personal Achievement Award. The twins, who have type 2 spinal muscular atrophy, are active leaders within their communities and in local MDA events.

As co-chairs of MDA's ALS Division, Augie and Lynne Nieto of Corona del Mar, Calif., helped raise awareness through public appearances, speaking engagements, media interviews and public service announcements.

In his fourth year of service, MDA National Youth Chairman Billy Gilman spearheaded the efforts of thousands of teenagers and young adults who help the Association's lifesaving mission. He performed and spoke at conferences for MDA sponsors DECA and ERA and at special events.

The 2006 National Goodwill Ambassador, 13-year-old Luke Christie of Due West, S.C., has type 2 spinal muscular atrophy. An eighth-grader, Luke is an excellent student who loves country music, reading, writing stories, acting and journalism. Luke and his family were profiled and interviewed on the national broadcast of the 2005 MDA Jerry Lewis Telethon, and since then have traveled the nation to thank volunteers and organizations for their support and spread the word about the Association's programs.

Selected pieces from the MDA Art Collection were exhibited at several locations across the country. The Collection includes more than 330 pieces from every state plus the District of Columbia and Puerto Rico, all by artists who have neuromuscular diseases. When not on tour, the Collection is on display at MDA National Headquarters in Tucson, illustrating to staff and visitors alike that physical disability is no barrier to creativity.