Novel method results in promising drugs for Huntington's disease therapeutics

Jan 26, 2011

Huntington's disease (HD) is an incurable progressive neurodegenerative genetic disorder which affects motor coordination and leads to cognitive decline and dementia.

The disease pathology stems from a mutation in the huntingtin (Htt) gene which results in the accumulation of toxic proteins leading to . Earlier studies have clearly implicated caspases, enzymes that break down cells, as key players in the cascade of events involved in HD neuronal death. Now scientists have identified three small molecules that inhibit the activity of those caspases, suppressing toxicity and rescuing neurons from cell death in cell culture.

The research, which appears in the November 24th edition of , was led by both Buck Institute faculty member Lisa Ellerby, Ph.D. and Yale University faculty member Jonathan Ellman, Ph.D. Dr. Ellerby is doing follow up studies in a mouse model of the disease.

Dr. Ellerby said a substrate based was used to identify compounds that reacted with caspases. Based on those reactions, Jonathan Ellman, Ph.D., from the Yale University Department of Chemistry, converted the compounds to caspase inhibitors.

Dr. Ellerby said that the inhibitors are based on properties of a drug which had entered Phase I clinical trials for the treatment of human liver preservation injury. "These molecules shows particular promise," said Ellerby. "They cross the blood-brain barrier and acts selectively to block the processes involved in HD." Dr. Ellerby said the caspase inhibitors both suppressed the proteolysis of Htt and rescued HD neurons that have begun to undergo cell death.

"We believe this is going to help us move the field forward because now we can test these compounds in live animals," said Dr. Ellerby. "Up until this point we have not identified a caspase inhibitor that has acted selectively against the toxic effects of the Htt mutation."

There is a desperate need for a treatment for HD. Symptoms of the disease usually begin to occur in middle age; patients are often totally incapacitated prior to death. The worldwide prevalence of HD is 5-10 cases per 100,000 people; the rate of occurrence is highest in peoples of Western European descent.

Explore further: Research milestone in CCHF virus could help identify new treatments

add to favorites email to friend print save as pdf

Related Stories

Protein in Huntington's linked to neurogenesis

Sep 02, 2010

EU-funded scientists have discovered that a mutated protein inherent in Huntington's disease (HD) performs an unforeseen role in neurogenesis. The finding could lead to a better understanding of HD, an inherited ...

Research links huntingtin to neurogenesis

Aug 11, 2010

New research finds that a protein that is often mutated in Huntington's disease (HD) plays an unexpected role in the process of neurogenesis. The research, published by Cell Press in the August 12 issue of the journal Neuron, provid ...

Protecting the brain from a deadly genetic disease

Feb 23, 2010

Huntington's disease (HD) is a cruel, hereditary condition that leads to severe physical and mental deterioration, psychiatric problems and eventually, death. Currently, there are no treatments to slow down or stop it. ...

Recommended for you

A new way to prevent the spread of devastating diseases

4 hours ago

For decades, researchers have tried to develop broadly effective vaccines to prevent the spread of illnesses such as HIV, malaria, and tuberculosis. While limited progress has been made along these lines, ...

New molecule allows for increase in stem cell transplants

5 hours ago

Investigators from the Institute for Research in Immunology and Cancer (IRIC) at the Université de Montréal have just published, in the prestigious magazine Science, the announcement of the discovery of a new molecule, the fi ...

Team explores STXBP5 gene and its role in blood clotting

8 hours ago

Two independent groups of researchers led by Sidney (Wally) Whiteheart, PhD, of the University of Kentucky, and Charles Lowenstein, MD, of the University of Rochester, have published important studies exploring the role that ...

User comments : 0