P4.55 Developing AMPA receptor aptamers as new drug candidates for ALS

Abstract

Developing aptamer drugs for a new therapy for amyotrophic lateral sclerosis (ALS) is our ultimate goal. The aptamers are nanomolar affinity, water-soluble RNA inhibitors of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors, a subtype of glutamate ion channel receptors. Excessive activation of AMPA receptors induces calcium-mediated excitotoxicity, one of the leading causes underlying the selective death of motor neurons in ALS. To date, we have successfully identified aptamers that inhibit every AMPA receptor subunit – these are competitive and noncompetitive type.