Growth Factor Promotes New Neuron Growth and Increased Survival in Mice with Huntington's Disease

Buck Institute study shows potential for new avenue of treatment for
incurable, hereditary brain disorder

November 28, 2005 Mice with Huntington’s disease (HD) grew a significant number of new neurons and lived longer after treatment with a well known growth factor. The research, to be published the week of November 28, 2005 in the on-line edition of the Proceedings of the National Academy of Sciences (PNAS), highlights a potential new therapeutic approach for a fatal, hereditary, degenerative brain disorder that affects approximately 30,000 Americans.

The mice, genetically engineered to develop HD, were treated with fibroblast growth factor-2 (FGF-2), a protein that has been shown to increase the growth of new blood vessels in human clinical trials. In the Buck study, the use of FGF-2 resulted in a 150 percent increase in new cells in the Huntington’s mouse brain, compared to a 30 percent increase in wild type mice (non-genetically engineered). Treatment extended the lifespan of the affected mice by 20 percent; the animals also exhibited improved motor performance, decreased cell death and a reduction in the amount of toxic aggregates that typically form in the brains of those affected by HD.

“Efforts to understand and encourage neurogenesis, the growth of new neurons, comprise an emerging area of study as we explore potential treatments for neurodegenerative diseases,” said Lisa Ellerby, PhD, lead scientist of the study. “In this case, the new brain cells migrated to the area of the brain affected by Huntington’s disease and assumed the features of the type of neuron commonly lost in HD,” said Ellerby. The FGF-2 was administered subcutaneously (by injection under the skin) to the mice, indicating that the protein can cross the blood-brain barrier, another factor that shows promise in the development of new therapies for the disease, according to Ellerby.

There is currently no effective treatment or cure for HD, which is typically characterized by involuntary movements and dementia. The disease slowly diminishes a person’s ability to move, think and communicate. Those affected eventually become totally dependent on others for their care and usually die from complications such as choking, heart failure or infection. The disease is hereditary; each child of a person with HD has a 50/50 chance of inheriting the fatal gene. Approximately 200,000 Americans are believed to be at risk of developing HD, a disease that affects as many people as hemophilia, cystic fibrosis or muscular dystrophy. The symptoms of HD typically begin to appear in mid-life, although the progression of the disease varies among individuals and within the same family.

”We welcome the encouraging knowledge generated by Dr. Ellerby’s study that FGF2 improves neurological function and longevity in HD transgenic mice,” said Carl Johnson, PhD, Executive Director for Science, Hereditary Disease Foundation. “ We look forward to further studies aimed at clarifying how FGF2 protects either through neurogenesis or through direct neuroprotection or both. These are promising studies and should be pursued,” said Johnson.

Nancy Wexler, President of the Hereditary Disease Foundation added, “Despite recent advances in understanding the pathogenesis of HD, therapeutics that significantly slow or stop the disease are lacking. We encourage research that facilitates the discovery and development of therapies and cures for Huntington’s disease."

Joining Ellerby as co-authors of the paper are Buck Institute scientists Kunlin Jin, MD, PhD; Michelle LaFevre-Bernt, PhD; Yunjuan Sun, MD;  Sylvia Chen, PhD; Juliette Gafni, PhD; Danielle Crippen, BA;  Anna Loginova, MD; and David Greenberg, MD, PhD along with Christopher Ross, MD, PhD, of the Johns Hopkins University School of Medicine.  The work was supported by grants from the National Institutes of Health, the Huntington’s Disease Society of America, the Hereditary Disease Foundation and the Muscular Dystrophy Association.

The Buck Institute is an independent non-profit organization dedicated to extending the healthspan, the healthy years of each individual’s life.  Buck Institute scientists work in an innovative, interdisciplinary setting to understand the mechanisms of aging and to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer’s and Parkinson’s disease, cancer, stroke, and arthritis. Collaborative research at the Institute is supported by genomics, proteomics and bioinformatics technology.

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