Natural product-derived differentiation agents for AML

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 2R44CA134089-02A1
Agency Tracking Number: R44CA134089
Amount: $853,202.00
Phase: Phase II
Program: SBIR
Awards Year: 2011
Solicitation Year: 2011
Solicitation Topic Code: NCI
Solicitation Number: PA10-050
Small Business Information
1100 CEDAR AVE, STE 285, CLEVELAND, OH, 44106-3007
DUNS: 801479333
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 MUKESH AGARWAL
 (216) 496-9053
 mukeshagarwal@inveniotherapeutics.com
Business Contact
 MUKESH AGARWAL
Phone: (216) 496-9053
Email: mukeshagarwal@inveniotherapeutics.com
Research Institution
 Stub
Abstract
DESCRIPTION (provided by applicant): Though AML is one of the most common forms of leukemia in adults; the 5 year survival is less than 20-50% in adults and significantly lowers in the elderly. The remarkable success in treating one relatively uncommon subset of AML, acute promyelocytic leukemia (APL), with all trans- retinoic acid (ATRA) illustrates the great promise for differentiation therapy. Utilizing ATRA, the presumed cure of 75-85% of patients is possible but only for this rare AML subset. ATRA's remarkable success stems from the fact that AML is a disease characterized by the arrest of differentiation of immature myeloid cells. ATRA overcomes this block in differentiation by forcing leukemic cells to mature. After leukemic cells undergo terminal differentiation, they lose their ability to proliferate. We have recently found that a plant-derived alkaloid holds promise as an AML therapeutic for non-APL leukemia due to its ability to induce potent AML differentiation. The major aims of this phase II project are to perform preclinical efficacy and toxicity studies in order to develop our optimized form of this plant-derived alkaloid into a clinical agent. As differentiation therapies are able to treat leukemia without the necessity for overt cytotoxicity,this work has the potential to lead to much needed more efficacious, less toxic, and better tolerated therapy for patients with AML. PUBLIC HEALTH RELEVANCE: This project is highly relevant to public health as its main objective is to develop a novel therapeutic regimen for patients with Acute Myeloid Leukemia that is both efficacious and has low toxicity. As current AML therapeutics has poor efficacy and high toxicities, there is a significant need for new therapies and therapeutic approaches for AML.

* Information listed above is at the time of submission. *

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