Assess the impact of AR reduction at later time points in KD – a crucial factor for all AR modifying therapeutics
Reward amount $75,000 plus $2,000 travel and education expenses for the 2024 Waite-Griffin SBMA Fellowship.
Summary Description
Research into potential therapeutic for Kennedy’s Disease (KD) have predominantly focused on therapeutic strategies that alter the functioning, signalling and expression of the polyglutamine-expanded androgen receptor (polyQ-AR). Previous studies have shown that when expression of the polyQ-AR is reduced, particularly in skeletal muscle, the disease phenotype is improved in animal models of disease, supporting the idea for reducing muscle AR for the treatment of KD. However, thus far, investigations of strategies to reduce or modify AR expression have only been carried out in pre-symptomatic time points in mouse models, demonstrating an effective prevention of the disease. This study will utilize our novel muscle specific AR silencing system, which we will use to assess the impact of AR reduction at later time points in KD – a crucial factor for all AR modifying therapeutics. We will also assess the effectiveness and safety of our novel approach as a potential therapeutic for KD, with the added advantage that our approach is muscle-specific. By restricting AR suppression specifically to muscle, we hope to prevent AR-reduction induced side-effects in organs where AR signalling is crucial for normal functioning.
These experiments will provide important proof-of-principle information as to how and when AR-silencing strategies can function as a therapeutic for KD.
BIO
Dr Annalucia Darbey joined the Fratta lab at UCL Queens Square Institute of Neurology as a Postdoctoral Research Fellow in 2021.
Her research focuses on using innovative and exciting technologies to develop tissue specific Gene Therapy solutions for Motor Neuron Diseases, particularly SBMA/Kennedy’s Disease. She has been fortunate to receive a number of awards whilst at UCL including a Cell & Gene Therapy TIN Award and an AFM Telethon award – these have been crucial for her continuing development as an ECR. Prior to her work at UCL, she completed her PhD in Tissue Repair & Gene Therapy at The University of Edinburgh before moving to Newcastle, Australia for two years to investigate Gene Therapy for endocrine disorders as a Postdoctoral Research Associate.
