NU2022-200
INVENTORS
Wanhao Chi
Jonathan Watts
Evangelos Kiskinis*
BACKGROUND
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative that leads to 1 in 500 deaths in adults. There is no cure to stop or reverse ALS, thus there is a need to better understand its pathobiology and develop effective therapeutics. Northwestern researchers have designed and identified antisense oligonucleotides (ASOs) for use in treatment of ALS and other neurodegenerative disorders. In more than 90% of ALS patients, a shared neuropathological feature is the trans-localization and aggregation of nuclear RNA-binding protein TDP-43, which further leads to the mis-splicing and depletion of target mRNAs. Genome-wide association studies have identified UNC13A as one of the prominent mis-spliced genes present in ALS patients. The research team designed 7 specific ASOs consisting of 10-30 nucleotides, that bind to the targeted intronic sequence encoding human UNC13A protein. In initial studies, ASOs administered in a cellular model for ALS successfully inhibited the mis-splicing of UNC13A. These ASOs are an effective method of suppressing UNC13A mis-splicing induced by TDP-43 dysfunction, and this approach has potential for therapeutic applications in ALS and other neurodegenerative disorders.
IP STATUS
A PCT application has been filed.