# Preclinical development of a Stathmin-2 splicing modulator for ALS > **NIH NIH R44** · QURALIS CORPORATION · 2020 · $499,987 ## Abstract PROJECT SUMMARY ALS is a devastating neurodegenerative disease with two FDA-approved therapies that can prolong a patient’s lifespan by only a few months. Thus, an effective therapeutic to treat ALS is needed. ALS can arise sporadically or through inherited mutations in one or a combination of several genes. The heterogeneity of ALS makes it difficult to create a therapeutic that can effectively treat a broad ALS patient population. However, many cases share a common pathological hallmark: the presence of the protein TDP-43 within neuronal inclusions. Recent research has shown that loss of normal TDP-43 function leads to the incorrect splicing of stathmin-2 (STMN2), a protein essential for neurite extension and maintenance of the neuromuscular junction. Indeed, in vitro evidence demonstrates that restoring STMN2 levels rescues motor neuron growth, and STMN2 protein levels are low in ALS patients. Since TDP-43 mislocalization and low STMN2 levels are common among sporadic and inherited ALS cases, STMN2 is a novel gene target to treat ALS. QurAlis has demonstrated that antisense oligonucleotides (ASO) can restore STMN2 RNA expression in a dose-dependent manner and can restore STMN2 protein levels in motor neurons derived from induced pluripotent stem cells lacking TDP-43. Since TDP- 43 regulation of STMN2 splicing only occurs in humans, no animal efficacy testing can be performed on our four Lead ASO candidates. Thus, with this proposal, QurAlis will develop a method for ASO detection after intrathecal ASO delivery and perform a dose-range finding study in rats (Phase I) and then with our Clinical Candidate ASO, validate the ASO detection assay and perform IND-enabling toxicology studies (Phase II). These studies will then allow QurAlis to file an IND with the FDA and begin a clinical trial testing the ASO efficacy in ALS patients. ## Key facts - **NIH application ID:** 10151251 - **Project number:** 1R44NS120604-01 - **Recipient organization:** QURALIS CORPORATION - **Principal Investigator:** DANIEL ELBAUM - **Activity code:** R44 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $499,987 - **Award type:** 1 - **Project period:** 2020-09-30 → 2021-03-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10151251 ## Citation > US National Institutes of Health, RePORTER application 10151251, Preclinical development of a Stathmin-2 splicing modulator for ALS (1R44NS120604-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10151251. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*