Molecular Horizons - Christen Chisholm, PhD Exit Seminar

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterised by the loss of motor neurons, resulting in muscle paralysis and death usually within 3 years of diagnosis. Despite over 200 clinical trials, there are currently no effective treatments.

A common pathological feature of ALS is the accumulation of misfolded and aggregated protein deposits within degenerating motor neurons. Therapeutic avenues to reduce or remove these toxic misfolded or aggregated protein species have been the focus of intensive research for the last two decades.

Modelled on proteolysis targeting chimeras (PROTACs), this presentation details the design of a novel antibody-based therapeutic tool that hijacks the cells natural protein degradation pathway to specifically reduce levels of toxic misfolded protein species.

We term this tool a “MisfoldUbL” as it specifically reduces misfolded proteins and acts via the ubiquitin ligase pathway. This presentation will reveal that the MisfoldUbL demonstrates both in vitro and in vivo therapeutic efficacy, providing a novel strategy for the treatment of ALS.