Islet Protection from Hypoxia Posttransplant

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$332,135.00
Award Year:
2010
Program:
STTR
Phase:
Phase I
Contract:
1R41DK075211-01A2
Award Id:
n/a
Agency Tracking Number:
R41DK075211
Solicitation Year:
2010
Solicitation Topic Code:
NIDDK
Solicitation Number:
PA08-051
Small Business Information
3408 Berkshire Cir, JOHNSON CITY, TN, 37604-
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
149048535
Principal Investigator:
KLEARCHOS PAPAS
(612) 626-0471
papas006@umn.edu
Business Contact:
WILLIAM STONE
(423) 439-8762
drbillstone@gmail.com
Research Institute:
University Of Minnesota

100 Church St Se
MINNEAPOLIS, MN, 55455-
() -
Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): Islet transplantation (ITx), especially with the emerging potential of xenotransplantation, holds significant promise for the treatment of type 1 diabetes (T1D). There are, however, major challenges that remain prior toits larger scale, cost-effective application. Hypoxia is a leading stress post-transplantation and is estimated to cause the death of approximately 40-50% of transplanted islets. Effective protection of transplanted islets from hypoxia-induced death (HID)has the potential to greatly enhance the success rate of ITx. Preliminary research in our labs demonstrated that alpha- and gamma-tocopherol and their succinate esters offer remarkable protection to porcine and human islets from HID at 24 hrs. Furthermorealpha- and gamma-tocopherol, when administered by injection starting 24 h pretransplantation, improved the cure rates of nude mice transplanted with the same islet mass as untreated controls by ~70%. Oral administration, if effective, would provide a preferred, more practical and safer alternative to injections. The objectives of this Phase I STTR are to: (i) Determine whether the succinate esters of alpha- plus gamma-tocopherol (which may provide additional advantages either as injectable or oral supplements) are equally or more effective than the corresponding tocopherols at the same and/or a lower dose when administered by intraperitoneal injections to diabetic nude mice transplanted with porcine islets; and (ii) Determine whether an oral administrationprotocol is an effective and efficacious alternative to injections. Because alpha- and gamma-tocopherol and alpha-tocopheryl succinate are approved for human consumption, this technology, if effective, can be rapidly evaluated for safety and incorporated in the clinical treatment of T1D. In Phase II, the effective compounds will be formulated for stability and tested for efficacy in preclinical islet transplantation models including nonhuman primates, which are well established at the University of Minnesota. The successful completion of the proposed work may lead to a significant, potentially breakthrough contribution in the development of islet transplantation as a safe and cost effective therapy for T1D by markedly improving islet viability post-transplantation. PUBLIC HEALTH RELEVANCE: This STTR can lead to a very safe product, which increases substantially the success rate of islet transplantation. This product can have reaching effects in advancing the practical use of islet transplantation in treatingType 1 diabetes. In addition to improving the quality of life and productivity of these patients, this product can help reduce the cost of health care.

* information listed above is at the time of submission.

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