Plant-derived differentiation agents for AML

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$142,460.00
Award Year:
2008
Program:
SBIR
Phase:
Phase I
Contract:
1R43CA134089-01
Award Id:
88929
Agency Tracking Number:
CA134089
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
INVENIO THERAPEUTICS, INC., 11000 Cedar Avenue, Suite 100, Cleveland, OH, 44106
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
801479333
Principal Investigator:
() -
Business Contact:
() -
davidwald@inveniotherapeutics.com
Research Institution:
n/a
Abstract
DESCRIPTION (provided by applicant): Plant-derived compounds, particularly alkaloids, have historically been a successful source of currently used therapeutics. Recently, a plant-derived alkaloid was identified that is a potent acute myeloid leukemia (AML) differentiation-inducing compound. Differentiation therapy for AML holds significant promise in leading to more efficacious and less toxic therapies. 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 lower in the elderly. The remarkable success in treating one relatively uncommon subset of AML, acute promyelocytic leukemia, with all trans-retinoic acid (ATRA) illustrates the great promise for differentiation therapy. Utiliz ing ATRA, the presumed cure of 75-85% of patients is possible. 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 for cing leukemic cells to mature. After leukemic cells undergo terminal differentiation, they lose their ability to proliferate. The aims of this phase I project are to 1) demonstrate the promise of a novel plant-derived alkaloid in a mouse xenograft model sy stem 2) demonstrate the activity of this compound and its analogues in vitro and 3) to identify novel plant-derived alkaloids with potent AML differentiation activity. As differentiation therapies are able to treat leukemia without the necessity for overt cytotoxicity, this work has the potential to lead to a 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 identify and dev elop novel therapeutics for patients with Acute Myeloid Leukemia that are better tolerated and more efficacious. As the prognosis for most patients with AML is currently poor, there is a significant need for new therapies.

* information listed above is at the time of submission.

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