University of California Irvine researachers, supported by the Hereditary Disease Foundation, successfully prevented cell death in their Drysophila fruit fly model that carried the HD gene. The team reported their announcement in the October 18th issue of the journal Nature [one of two premier science journals in the world - ed. note]. The team successfully prevented cell death in their fruit fly that carried the HD gene. Most promising of all, the drugs they used to protect the fly eye are currently in clinical trials for treatment of cancer in humans.
The medications are already approved by the Food and Drug Administration (FDA) for cancer research in human populations, and possibly may be of use in clinical trials for Huntington's disease and other similar progressive, neurodegenerative disorders.
Huntington's disease affects more than 100,000 people in the United States. Thirty-five thousand individuals are symptomatic and another 75,000 people carry the abnormal gene and will definitely manifest the disease in the future. Preventing the disorder before a person shows symptoms is probably the most effective treatment possible. The Irvine team achieved this result in their flies.
Leslie Thompson and Joan Steffan of the College of Medicine, Lawrence Marsh of the School of Biological sciences, and colleagues studied the genetic and molecular interactions in the disease and found that chemicals called histone deacetylase (HDAC) inhibitors might counteract the course of Huntington's and possibly other progressive, neurological disorders. The scientists found that HDAC inhibitors curbed neuronal degeneration caused by the genetic mutations that lead to Huntington's disease.
While there is presently no cure for Huntington's disease, we believe we have
traced one way that the mutation alters chemical pathways to cause the disease,
" Dr. Thompson said. By reversing key changes in these pathways, we have
identified a potentially effective way to slow or prevent the disease. What's
especially exciting is that existing drugs known as
HDAC inhibitors have the potential to provide this treatment.
The researchers found that the mutant form of the protein called “huntingtin" -or htt -which results from genetic changes causing Huntington's disease, inhibits the actions of several other proteins whose normal function is essential for normal brain cells. The mutated form of huntingtin stifles the activity of key enzymes called acetyltransferases (ATs). The huntingtin protein reduces the levels of these acetyl-transferases and related proteins, resulting in the nerve cell damage seen in the diseased brain.
Cells in our body normally maintain a balance between the opposing forces of AT enzymes that modify proteins to increase genetic activity and HDAC enzymes that reverse these modifications to reduce gene activity. Since the mutated huntingtin protein destroys this balance, the researchers sought to restore the balance by reducing the HDAC activities to compensate. The HDAC inhibitors were able to prevent neuronal damage in fruit flies that were engineered to carry a disease-producing form of human-huntingtin.
"While presently we can't eliminate the genetic mutation that ultimately causes Huntington's disease, this study indicates that we may be able to reduce significantly the effects of that mutation," Marsh said. "Our study also points the finger at a complexion of genes and tells us what we need to do next. Perhaps we can find even better and more precisely targeted strategies to help this disease. If this strategy proves effective in other animals such as mice, we will still need to know when to administer such a drug, how to administer it and what the long-term side effects may be."
“We are extremely excited by these dramatic findings that could have immediate therapeutic relevance," said Dr. Nancy Wexler, President of the Hereditary Disease Foundation .
In addition to the primary support from the Hereditary Disease Foundation, support came from the Huntington's Disease Society of America, Human Frontier Science Program and the National institutes of Health.
Created and maintained by Renette Davis. Send comments to Renette by clicking here.
Created: Aug. 11, 2003
Last updated: Nov. 14, 2010