Professor Li Niu Awarded Three-Year Grant for ALS Drug Research

Professor Li Niu, Department of Chemistry, has been awarded a three-year, $405,000 grant from the Muscular Dystrophy Association for his project “Characterization of Chemically Modified Aptamers as New ALS Drug Candidates”.

Amyotrophic lateral sclerosis (ALS) is the most common adult motor neuron disease and is also the most lethal neurodegenerative disease. ALS results in the degeneration of motor neurons in the cortex, brainstem and spinal cord. As a result, the brain loses the ability to control muscle movement. Early symptoms of ALS often include increasing muscle weakness and difficulty in swallowing and breathing. ALS was first described in 1869 by French neurologist Jean-Martin Charcot, but it was Lou Gehrig who brought special attention to this disease (ALS is also called Lou Gehrig’s Disease in US). Lou Gehrig played for the Yankees, and his career was cut short in 1939 by ALS. Today, the cause for the majority of the disease is unknown, but is thought to involve both genetic and environmental factors. There is no effective cure or treatment.

Dr. Niu’s project will build on the previous research in which his lab identified special RNA molecules or RNA aptamers. These aptamers target and inhibit a particular subtype of glutamate ion channels called AMPA receptors in the central nervous system; excessively active AMPA receptors have been implicated in the pathogenic mechanism for ALS. Dr. Niu’s prior research involved designing chemically modified aptamers that would resist ribonucleases, the enzymes that catalyze RNA degradation. Without these modifications, the therapeutic application of aptamers would be limited.

The goal of Dr. Niu’s project is to characterize these chemically modified RNA aptamers for their neuroprotective effectiveness on glutamate-induced neurotoxicity in ALS cellular and animal models. This research is important to prove that developing biostable, AMPA receptor-selective aptamers is a novel drug design strategy for ALS, and even other neurological disorders and diseases. Dr. Niu hopes to demonstrate that these aptamers are promising drug candidates for an effective ALS therapy. The successful completion of this project will be the key benchmark towards advancing the aptamers into clinical trials.