Area:
Synaptic Plasticity, Hippocampus
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High-probability grants
According to our matching algorithm, Eric A. Horne is the likely recipient of the following grants.
Years |
Recipients |
Code |
Title / Keywords |
Matching score |
2012 — 2013 |
Horne, Eric Andrew |
R43Activity Code Description: To support projects, limited in time and amount, to establish the technical merit and feasibility of R&D ideas which may ultimately lead to a commercial product(s) or service(s). |
Targeting a New Gpcr to Treat Glioblastomas @ Stella Therapeutics, Inc.
DESCRIPTION (provided by applicant): There is an urgent need for novel therapies to treat malignant astrocytomas, the most common and aggressive primary tumor of the nervous system. Using current standard of care, patients diagnosed with these tumors have an average life expectancy of 18 months and there is no effective treatment available. The laboratory of Dr. Nephi Stella recently discovered a new subclass of indole compounds that activate GPR124, a GPCR with established relevance in tumor pathogenesis. These indoles demonstrate efficacy in both in vitro and in vivo rodent models of malignant astrocytomas. Notably, the therapeutic effective doses of indoles do not produce overt toxicity in mice. The goal of Stella Therapeutics is to develop drugs that target GPR124 and efficiently treat malignant astrocytomas with minimal side-effects. In this proof-of-concept work, we will: Aim 1: Validate an in vitro assay tha measures the potency of GPR124 agonists in human astrocytoma cells. Use this assay to screen 40 analogues of NMP-192 (EC50 = 54 nM). Aim 2: Select the 2 most promising compounds and establish their pharmacokinetic and acute toxicity profiles in mice, as well as measure their in vivo efficacy in a xenograft mouse model of malignant astrocytomas. By the end of this Phase I SBIR, Stella Therapeutics will have developed a lead compound that activates GPR124, exhibits in vivo efficacy and induces minimal side effects. The resulting phase II SBIR will further optimize the drug-like properties of the lead compound by using state-of-the-art medicinal chemistry and chemo-informatics. We will systematically measures their therapeutic efficacy and side effects to establish a therapeutic index. Stella Therapeutics is dedicated to developing and patenting novel drug-based therapies to treat malignant tumors. PUBLIC HEALTH RELEVANCE: There is an urgent need for novel therapies to treat malignant astrocytomas, the most common and aggressive primary tumor of the nervous system. This phase I SBIR outlines a strategy to develop a new therapeutic approach to treat these tumors. By combining the strength of several state-of-the-art approaches in drugs development, we will develop small molecules that activate a novel therapeutic target expressed by malignant astrocytomas. Stella Therapeutics is dedicated to developing and patenting novel drug-based therapies to treat malignant tumors.
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