Scientists from around the nation have come together through the initiative of the University of Rochester Medical Center in a coordinated national effort to pursue a new treatment for Parkinson's disease.
The five-year program to lay the groundwork for a gene therapy treatment for the disease is funded with $8.8 million from the National Institute of Neurological Diseases and Stroke (NINDS), which took the unusual step of requesting the application for the project after Rochester neuroscientists first sketched out the idea.
The program aims to pioneer a new way to treat Parkinson's disease. Although a variety of treatments exist today, including different forms of surgery as well as several medications, none halts the inevitable decline caused by the disease. The one million patients with the disease in North America typically have tremors, rigid movements, problems with swallowing, and a variety of other symptoms that worsen over a period of years or even decades.
The team pulled together by Rochester neuroscientist Howard Federoff, M.D., Ph.D., has brought many of the world's Parkinson's experts together to embark upon a new approach. Scientists and physicians are working together to identify the most promising strategies for manipulating genes to alleviate and perhaps even reverse symptoms in patients. Researchers from seven institutions around the country -- an all-star team of Parkinson's researchers -- are pursuing several avenues of research.
"Our goal is to bring forward, in the most rigorous possible fashion, a gene therapy for patients with Parkinson's disease," says Federoff, chief of molecular medicine and gene therapy and director of the Center for Aging and Developmental Biology. "We're proceeding deliberately and cautiously to develop and test new treatments, in a coordinated progression from basic research to preclinical evaluation to clinical testing. Our intention is to lay the groundwork for a future study where new approaches can actually be tested in people."
The new group, known as the Parkinson's Disease Gene Therapy Study Group, is made up of researchers from the University of Rochester, Northwestern, Rush-Presbyterian Medical Center in Chicago, Yale, and University of California campuses in Irvine, Los Angeles, and San Francisco
"This is an unprecedented comprehensive program, and everyone involved has made a substantive commitment to this effort," says Federoff. "These investigators have demonstrated a remarkable willingness to set personal agendas aside and work within an organization designed to support the common goal of advancing gene therapy for Parkinson's disease."
Neuroscientists will work on ways to shuttle genes into cells, along with methods to turn on and off those genes exactly when and where they want. Viruses that cause cold sores and the common cold and other maladies are among the molecular tools scientists are developing for this purpose. Such viruses are at the heart of a "molecular toolbox" that scientists hope will enable them to alter brain cells to counter in Parkinson's patients the effects of the shortage of a brain chemical known as dopamine.
By the time a patient notices symptoms of the disease and goes to the doctor, more than 80 percent of the brain cells that produce dopamine have already died. Gene therapy might be used to generate more dopamine in the brain of a patient, or to create chemicals that help injured brain cells live longer than they otherwise would. It could also help doctors deliver crucial brain chemicals precisely where they want, decreasing patients' reliance on medicines and reducing side effects.
While the idea of manipulating genes to boost human health -- gene therapy -- has been around for more than two decades, actually implementing the idea has proven difficult for researchers. Only a handful of patients worldwide have been treated with the technique. Yet with the human genome mapped, most scientists believe that manipulating genes to treat or prevent disease will be common in the future. This study is the first to focus on gene therapy as a treatment for a disease where neurons die, such as Parkinson's, Alzheimer's, Huntington's, or Lou Gehrig's diseases.
While neuroscientists do the fundamental molecular research, other researches will study the issues that lead people to volunteer for the early phases of medical research studies. Bioethicists will explore why people consider participating in such studies, how much risk they find acceptable, and whether they overestimate the benefits of participation.
The five-year study is the result of more than three years of planning by Federoff and colleagues. In the past Federoff has advised Federal officials on the best ways to use funding dollars to spur research on Parkinson's disease, and he has helped the U.S. Army formulate its approach to funding for the disease. He has appeared before a Congressional Committee and last year organized a major national meeting for the New York Academy of Sciences. He has been a pioneer in learning how some pesticides destroy brain cells in the same way as Parkinson's disease does, and recently his laboratory created some of the first mice that mimic the disease in humans. He was also the first to discover a way to manipulate and exert pinpoint control over genes in the nervous system.
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