CHICAGO --- Northwestern University, the University of California-San Francisco and RheoGene, Inc., have received a grant from the Michael J. Fox Foundation for Parkinson’s Research that will provide up to $4.2 million for development of a regulatable gene therapy system to treat Parkinson’s disease.
Martha Bohn, a leading authority on gene therapy approaches to treat Parkinson’s disease, is Medical Research Council Professor and director of the neurobiology program at Children’s Memorial Research Center and professor of pediatrics and of molecular pharmacology and biological chemistry at Northwestern University Feinberg School of Medicine.
Biotechnology company RheoGene, Inc., will test a novel gene regulation technology, the RheoSwitch® system, using a gene that codes for a protein known as glial cell line-derived neurotrophic growth factor (GDNF) to treat Parkinson’s disease and another gene designed to replace an enzyme in the brain that declines in Parkinson’s disease.
The Bohn lab will test the gene switch in the brain of rodent models of Parkinson’s disease. Researchers at UCSF will conduct similar studies in a different animal model.
Unlike earlier gene therapy delivery systems, the RheoSwitch® allows precise control of both the level (dose) and timing (on/off) of gene expression (protein production) to be precisely controlled through the oral administration of a so-called “activator drug” in pill form.
“The planned studies promise to make gene therapy safer for a variety of diseases, and will accelerate advancement into treating patients,” Bohn said.
Development of gene therapy as a widespread therapeutic technique has been hampered by the lack of any way to time or finely adjust doses or to “turn off” a gene once it starts expressing a protein in the brain.
With the RheoSwitch® system, production of genetic proteins can be completely shut off by withdrawal of an activator drug, providing a non-toxic mechanism to halt gene expression in the event of serious gene therapy side effects.
The National Institutes of Health estimate that up to 1.5 million Americans have Parkinson’s disease.
In Parkinson’s disease, dopamine-producing neurons in the brain degenerate, resulting in gait problems, muscle rigidity and tremors.
Bohn’s laboratory group discovered that glial cells in the embryonic brain stem secrete factors, or proteins, that promote survival and differentiation of dopamine neurons.
GDNF is a potent factor that promotes growth of not only dopamine neurons, but also motor neurons and several other types of neurons. Bohn and other researchers believe that GDNF may have therapeutic potential for several neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis, commonly known as Lou Gehrig’s disease.
Bohn’s laboratory was the first to show that introduction of a GDNF gene in a rodent model of Parkinson’s disease halts the disease process.
Founded in 2000, The Michael J. Fox Foundation for Parkinson’s Research is dedicated to ensuring the development of a cure for Parkinson’s disease within this decade through an aggressively funded research agenda. To date, the foundation has funded more than $60 million in research.