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A small molecule integrin activator to enhance cord blood transplant

Award Number: R41HL129612
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2016
PERIOD OF PERFORMANCE END DATE: 04/30/2019

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A small molecule integrin activator to enhance cord blood transplant - ¿ DESCRIPTION (provided by applicant): This proposal is in response to PA-15-270, the parent announcement for STTR (R41) grant applications. Hematopoietic stem cell transplantation has become a preferred treatment for hematological malignancies and certain genetic disorders. The use of umbilical cord blood cells as a source of hematopoietic stem cells for bone marrow transplantation has increased steadily over the last decade. Due to a less stringent HLA match requirement, cord blood transplant has allowed patients to be treated that otherwise could not find a suitable donor. Unfortunately, there are fewer stem cells in these preparations which results in delayed rates of immunological reconstitution. This can lead to a higher incidence of opportunistic infections which increases the rate of graft failures and transplant related mortalities. Finding a means to improve the rate of immune reconstitution with cord blood transplants would translate to improved outcomes as well as broader applicability to adult patients. Efforts to improve the rate of engraftment of cord blood cells include targeting the cell adhesion cascade which mediates cell homing, extravasation and retention in the bone marrow. This process is coordinated through the function of chemokines as well as the selectin and integrin families of cell adhesion molecules. Promising results have been generated by treating the cells ex-vivo to improve the function of the selectin- and chemokine-mediated processes. A drawback to these preconditioning steps is they require additional time, expertise and expense. As yet the integrins have not been targeted due to a lack of suitable reagents. We have developed a unique small molecule that can activate integrins on cord blood cells, facilitating their interaction with their counter-receptors in the bone marrow. This compound can enhance all phases of the adhesion cascade including cell rolling, firm adhesion, and migration. It binds to the integrin directly and activation takes place instantaneously. As a result, no extensive preconditioning of the cells is necessary. This proposal outlines proof-of-concept studies to evaluate the compound in xenogeneic animal models to determine its effect on cord blood cell homing and engraftment in the bone marrow following transplant.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2016	7 HILLS PHARMA LLC	8285 EL RIO STE 130	HOUSTON	TX	77054	HARRIS	USA	Cardiovascular Diseases Research	000	1	5/7/2019	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2016	7 HILLS PHARMA LLC	2126 SHERIDAN ST	HOUSTON	TX	77030	HARRIS	USA	Cardiovascular Diseases Research	000	1	3/15/2018	NEW	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $295,931 )
2016	2016	7 HILLS PHARMA LLC	2126 SHERIDAN ST	HOUSTON	TX	77030	HARRIS	USA	Cardiovascular Diseases Research	000	1	8/27/2016	NEW	$295,931
														Subtotal = $295,931

Grand Total All Awards = $295,931

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A small molecule integrin activator to enhance cord blood transplant

Award Number: R41HL129612

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2016

PERIOD OF PERFORMANCE END DATE: 04/30/2019

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