UNC13A is an essential regulator of neurotransmitter release at synapses; mis-splicing is critical genetic alteration occurring in 58 percent of all ALS patients and up to half of all FTD cases
Preclinical data to be featured in an oral presentation at 34th International Symposium on ALS/MND
CAMBRIDGE, Mass., Nov. 29, 2023 /PRNewswire/ -- QurAlis Corporation, a clinical-stage biotechnology company driving scientific breakthroughs into powerful precision medicines that will alter the trajectory of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative diseases, today announced it will present preclinical data showing that TDP-43 (TAR DNA-binding protein 43) pathology drives loss of synaptic UNC13A function in neurodegenerative diseases including ALS and FTD. Data also showed that an UNC13A splice-switching antisense oligonucleotide (ASO) prevented cryptic exon inclusion in UNC13A transcripts, increased UNC13A protein levels, and normalized localization of UNC13A protein at the synapse.
UNC13A is an essential regulator of neurotransmitter release at synapses and is one of a number of pre-mRNAs that becomes mis-spliced due to loss of nuclear TDP-43 in disease. Fifty-eight percent of ALS patients and up to half of FTD patients carry a single nuclear polymorphism in the UNC13A gene or show TDP-43 pathology which greatly exacerbates UNC13A mis-splicing leading to loss of function of the UNC13A protein.
These data will be featured in an oral presentation at the 34th International Symposium on ALS/MND being held December 6-8, 2023, in Basel, Switzerland and virtually. Details of the presentation are as follows:
Title: UNC13A Loss and TDP-43 Dependent Mis-splicing Drives Synaptic Dysfunction in FTD and ALS
Date/Time: Wednesday, December 6, 2023, 5:00PM CET
Abstract Number: C30
Session: 4A Cell Biology and Pathology
Presenter: Sandy Hinckley, Ph.D., senior director, head of discovery, QurAlis
Incorporating its proprietary FlexASO™ Splice Modulator Platform, QurAlis' ASOs correct UNC13A mis-splicing, restore UNC13A protein production, and reduce cryptic exons that may contribute to disease progression. The QurAlis FlexASO Splice Modulator Platform was developed to generate splice-switching ASOs with improved potency and an increased therapeutic index. In addition to UNC13A, QurAlis is currently exploring this ASO technology for multiple other disease targets.
There are currently no cures for ALS or FTD. Limited therapeutic options are available for ALS and FTD patients who are in desperate need for effective therapies.
About QurAlis Corporation
At QurAlis, we are neuro pioneers on a quest to cure. We work with a relentless pursuit of knowledge, a precise attention to craft, and an optimistic mindset to discover and develop effective precision medicines that will alter the trajectory of amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative diseases. Founded by an internationally recognized team of neurodegenerative biologists from Harvard Medical School and Harvard University, QurAlis is advancing a pipeline with therapeutic candidates that target specific components of ALS and FTD pathology and defined patient populations based on both disease-causing genetic mutation(s) and clinical biomarkers. For more information, please visit www.quralis.com or follow us on Twitter @QurAlisCo.