A drug repurposing strategy to inhibit AR transcriptional coactivators as a therapeutic approach in SBMA
Kennedy’s disease is a neuromuscular condition caused by a mutation in the androgen receptor (AR). AR is a transcription factor, which means that it controls what the cells need to transcribe or not to stay healthy. It does that by interacting with other proteins called transcriptional coactivators. The mutation leads to a protein with altered functions; some are lost, others are enhanced. We have collected interesting evidence that by modulating the interaction with two specific AR partners that are increased during the disease, we can reduce the aberrant AR activity and preserve its normal function. We propose to investigate how the enhancement of these two factors contributes to motor neuron and muscle pathology. At the same time, we propose to use safe and well-tolerated drugs that inhibit these two factors to test whether this could be a successful therapeutic approach for the patients.
