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Novel Hematopoietic Conditioning Agents for Treatment of Hematological Diseases
- Small Business Information
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Woman-Owned: NoMinority-Owned: NoHUBZone-Owned: No
- Phase 1
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Fiscal Year: 2010Title: Novel Hematopoietic Conditioning Agents for Treatment of Hematological DiseasesAgency: HHSContract: 1R43HL099249-01Award Amount: $112,885.00
Abstract:
DESCRIPTION (provided by applicant): Hematopoietic stem cell transplantation (HSCT) has increased the survival of children and adults afflicted with malignant and non-malignant hematological diseases. Prior to transplant, patients receive a conditioning re gimen of cytotoxic drugs (e.g. cyclophosphamide/busulfan) and/or total body irradiation in order to suppress the immune system and, in the case of malignancies, eradicate remaining cancer cells. Unfortunately, conditioning drugs and radiation are not speci fic for the hematopoietic system or cancer cells but also damage normal tissues (e.g. liver, lungs and kidneys, oral mucositis), suggesting that developing conditioning agents that specifically target hematopoietic cells (normal and malignant) may have cli nical benefit. Using a cell-based readout system, we have identified a small molecule (SM27) that selectively kills cells of hematopoietic origin, including a panel of human leukemia cell lines, normal human blood cells and mouse bone marrow cells. Our pre liminary screening provides proof-of-principle evidence that specific targeting of the hematopoietic system is feasible. However, the maximum activity of SM27 is at 5M concentrations and the molecule is structurally unstable (e.g. contains an ester linkage ). Therefore, the goals of this proposal are 1) to structurally optimize SM27 using synthetic chemistry to modify portions of the molecule that may be responsible for instability, 2) to identify additional hematopoietic-specific agents through the screenin g of novel chemical libraries (250,000+ compounds) and 3) to characterize hits against a wide panel of human cancer cell lines of hematopoietic and non-hematopoietic origina as well as normal human tissue cells (lung, kidney, liver, oral, bone marrow) know n to be targeted or damaged by standard conditioning regimens in order to identify potential lead compounds that are highly hematopoietic-specific. The significance of this project lies in its potential for developing a less toxic conditioning regimen for HSCT for treatment of hematological diseases. The results of this proposal have major implications for all patients requiring HSCT for the treatment of malignant and non-malignant hematological diseases. PUBLIC HEALTH RELEVANCE: Hematopoietic stem c ell transplantation (HSCT) has improved the survival rates of high-risk and relapsed patients suffering from malignant and non-malignant hematological diseases. However, conditioning regimens used to prepare patients for HSCT are not specific to cells of h ematopoietic origin and thus can cause damage to liver, lung, kidneys and other tissues leading to short-term and long-term complications that can be potentially fatal. The development of hematopoietic-specific conditioning agents should provide a less tox ic alternative to current regimens and, thus, has major implications for patients receiving HSCT for the treatment of hematological diseases.Small Business Information at Submission:TARTIS, INC.
384 SUMMER STREET BUFFALO, NY 14213EIN/Tax ID: 126451843DUNS: N/ANumber of Employees: N/AWoman-Owned: NoMinority-Owned: NoHUBZone-Owned: No
Award Information
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Agency: Department of Health and Human Services |
Branch: N/A |
Award ID: 96326 |
Program Year/Program: 2010 / SBIR |
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Agency Tracking Number: HL099249 |
Solicitation Year: N/A |
Solicitation Topic Code: NHLBI |
Solicitation Number: N/A |