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By Greta Petry (February 15, 2007)

Huang Wins Muscular Dystrophy Association Grant

Zhen Huang, Ph.D., and Amy Novakovic.

Zhen Huang, Ph.D., and Amy Novakovic. Huang is a postdoctoral fellow in the lab of Professor Li Niu of the Department of Chemistry. (Photo by Mark Schmidt)

Zhen Huang, Ph.D., recently won a $135,000 grant from the Muscular Dystrophy Association for his research on identifying RNA aptamers as drug candidates for neurodegenerative diseases such as ALS.

His grant is sponsored by Professor Li Niu of the Department of Chemistry. Huang is a postdoctoral fellow in Niu's laboratory.

"The goal of my MDA-funded project is to identify new, powerful RNA inhibitors called aptamers against glutamate receptor channels from a library containing billions and billions of RNA molecules. These aptamers are potential candidates for the development of new drugs for ALS therapy," Huang said.

ALS, or Lou Gehrig's disease, is also known as amyotrophic lateral sclerosis.

Huang and the researchers in Niu's lab in the Life Sciences Research Building are studying a special family of proteins – glutamate ion channel receptors – that are indispensable to brain functioning such as memory and learning. The abnormal behavior of these channels has been implicated in stroke, epilepsy, and neurodegenerative diseases such as ALS.

Currently, in more than 90 percent of ALS cases, there is no known cause, and there is no effective cure. Riluzole, the only drug available, prolongs a patient's life on the average of two months. However, the life expectancy of ALS patients is only about three years after proper diagnosis.

Huang, who joined UAlbany in April 2003, was awarded a postdoctoral fellowship from MDA for three years.

He came to UAlbany from Xiamen, China, and was at Wuhan University prior to that.

Excessive receptor activation is believed to be toxic to motor neurons in the spinal cord, and has been suggested as a major contributing factor to ALS, Huang said.

In normal neurotransmission, glutamate molecules bind to the glutamate ion channel receptors and then open the ion channels. The channels act as corridors to allow calcium ions to pass through the cell membrane.

However, excessive activation of these glutamate channels causes too many calcium ions to enter the cell. The result is calcium overload, which induces cell death. Gradually, the patients lose control of their motor neuron functions. "The phenomenon is thought to be one of the leading hypotheses responsible for the selective motor neuron degeneration linked to ALS," Huang said.

Niu's lab is using an interdisciplinary approach, including the systematic evolution of ligands by exponential enrichment (SELEX) and a rapid laser-pulse photolysis technique, to develop the RNA molecules that can inhibit these glutamate receptors.

"Technically, we are 'fishing out' useful RNA molecules from a very large RNA pool," Huang said. "We hope to obtain nanomolar affinity, high-specificity RNA inhibitors targeting the glutamate receptors. These RNA molecules are expected to have much better properties than chemically synthesized inhibitors as drug candidates."


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