Disease Focus: Amyotrophic Lateral Sclerosis
Role of ataxin-3 polyadenylation site selection in ALS neuron toxicity and disease pathogenesis
Research Objective Here we will study the role of ataxin-3 alternative polyadenylation in the pathogenesis of ALS, and test if ASOs can reduce distal polyadenylation of ataxin-3 to rescue ALS disease phenotypes Impact Our goal is to determine if ataxin-3 genetic dysregulation is a target for the development of therapies to treat ALS (Lou Gehrig's […]
Developing a Human Model of Sporadic ALS Using Machine Learning and Robotic Microscopy
Research Objective We will develop the first human stem cell model of sporadic ALS (sALS) to identify disease mechanisms in the most common form of ALS and to discover drugs to treat the vast majority of ALS patients. Impact Failure of drugs to treat sALS may be due to the use of models of familial […]
Development of a VAV2 antisense oligonucleotide (ASO) treatment for ALS
Research Objective Patient specific stem cells (iPSCs) to model ALS and identify a broadly acting therapeutic intervention Impact Heterogenous patient population, dire need for broadly acting therapeutic interventions Major Proposed Activities Compare the in vitro efficacy of up to 10 lead candidate VAV2 ASOs to rescue the survival of iNs from 30 locally and nationally […]
C9orf72 repeat expansion-tuned allelic suppression by CRISPRi as an ALS therapy
Research Objective We aim to discover an adeno-associated viral (AAV) CRISPRi gene therapy for amyotrophic lateral sclerosis (ALS) patients with hexanucleotide repeat expansions in the C9orf72 gene. Impact This therapy can be administered intravenously once, have long lasting effects, and is indicated for all ALS patients who carry repeat expansions of varying lengths and toxicity […]
Development of a new therapeutic for directing target specific stem cell migration and treatment
Research Objective A drug-stem cell combination therapy wherein the drug will direct and promote the delivery and distribution of stem cells to the disease site for the optimal therapeutic effect of the stem cells Impact Amyotrophic lateral sclerosis (ALS) and the way to deliver and enhance stem cell-based treatment of ALS Major Proposed Activities Complete […]
Development of a SYF2 antisense oligonucleotide (ASO) treatment for ALS
Research Objective We will develop an antisense oligonucleotide, or DNA therapy for diverse forms of amyotrophic lateral sclerosis (ALS). Impact ALS is fatal and incurable, and if successful, we will develop a treatment that slows or stops ALS progression across a broad range of patients. Major Proposed Activities Selection of the lead drug by testing […]
Development of AS-241, an UNC13A Targeting Antisense Oligonucleotide (ASO) Treatment for ALS, for IND-enabling Studies
Translational Candidate AS-241, an antisense oligonucleotide Area of Impact Amyotrophic Lateral Sclerosis Mechanism of Action AS-241 targets the cryptic exon (CE) of UNC13A and suppresses CE inclusion during RNA splicing, inhibits nonsense-mediated decay, and increases full length mRNA and protein levels Unmet Medical Need To date, therapeutic options for ALS have been limited, and disease-modifying […]
Human Embryonic Stem Cell-Derived Neural Stem Cell Transplants in Amyotrophic Lateral Sclerosis
Translational Candidate Spinal cord injections of human embryonic stem cell (hESC)-derived allogeneic neural stem cells (heNSCs) for treatment of ALS Area of Impact Treatment of Amyotrophic Lateral Sclerosis (ALS) Mechanism of Action Although the exact molecular mechanism of action is unknown, extensive research supports the concept that the behavior of defective astrocytes is key to […]