Similarities between genetic diseases create hope for treatment (12/29/2007)

Two rare neurodegenerative diseases -- Huntington's disease and spinocerebellar ataxia 1 - share genetic modifiers in the cellular pathways that cause nerve cell damage, a fact that may make studying them and developing treatments more attractive to biotech companies, said a Baylor College of Medicine researcher.

A report on the research led by Dr. Juan Botas, associate professor of molecular and human genetics at BCM, appears in the current issue of the journal Human Molecular Genetics.

"We found commonalities in the diseases," he said. "These diseases are not like Alzheimer's disease or Parkinson's, which affect many patients. Often these rarer diseases get less attention in the media or from pharmaceutical companies, but they are no less devastating."

Symptoms of both these diseases show up in adulthood. They are both polyglutamine disorders. Expansion of DNA repeats encoding glutamine within the genes for each disease - ataxin-1 for the ataxia and huntingtin for Huntington's - spell disaster for how the protein is used by the cell. While studies indicate that the repeats interfere with the proper folding of the proteins encoded by the genes, other research indicates that other factors specific to each disease are involved.

When Botas and his colleagues compared the two diseases in models in Drosophila, or fruit flies, they found that some genes that modify the neuronal toxicity of ataxin-1 and huntingtin function similarly in both insect models of the diseases. In contrast, others have opposite effects, suppressing toxicity in one case and enhancing it in another.

Some of the genes that they found affect RNA (ribonucleic acid) metabolism, or its production, modulating the toxic effect of the proteins ataxin and huntingtin on nerve cells.

The genes that have opposite effects on the neuronal toxicity of ataxin-1 and huntingtin might help identify differences in how the two proteins affect nerve cells negatively, he said.

The modifier genes ameliorating the neuronal toxicity of both ataxin-1 and huntingtin, and their corresponding cellular pathways, might point to targets for drugs in both diseases, said Botas.

Others who took part in this research include Joana Branco, Ismael Al-Ramahi, Lubna Ukani, Alma M. Perez, Pedro Fernandez-Funez and Diego Rincón-Lima, all of BCM. Funding for this work came from the National Institutes of Health and the Portuguese Foundation for Science and Technology.

This paper is available at http://hmg.oxfordjournals.org/cgi/reprint/ddm315v1

Note: This story has been adapted from a news release issued by Baylor College of Medicine

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