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NO-donor/SOD-mimetics for diabetic nephropathy

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43DK069128-01
Agency Tracking Number: DK069128
Amount: $134,000.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: PHS2005-2
Timeline
Solicitation Year: 2005
Award Year: 2005
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
Mandalmed, Inc. Lakeside Medical Center
San Francisco, CA 94132
United States
DUNS: N/A
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 ELWOOD REYNOLDS
 (415) 333-5570
 ELWOODROW1@EARTHLINK.NET
Business Contact
Phone: (415) 333-5570
Research Institution
N/A
Abstract

DESCRIPTION (provided by applicant): Vascular disease is the principal cause of morbidity and mortality in patients with diabetes, leading to nephropathy, retinopathy, neuropathy, and ischemic disease. Hyperglycemic damage to vascular endothelial cells is a major cause of these vascular complications of diabetes. This endothelial dysfunction is caused by oxidative stress induced by hyperglycemia, resulting in both the increased production of reactive oxygen species (ROS) and decreased bioavailability of nitric oxide (NO). Hyperglycemia also causes similar oxidative stress in renal mesangial cells, which leads to mesangial matrix expansion, glomerosclerosis, and renal functional impairment. We have developed a novel drug for treatment of hyperglycemia induced endothelial and mesangial cell dysfunction. OX029 is a bifunctional NO-donor/SOD-mimetic which is a derivative of lipoic acid, The major goals of this proposal are to (1) determine the efficacy of OX029 to prevent endothelial dysfunction and renal injury in the diabetic streptozotocin-treated rat, and (2) design and synthesize 20 novel analogs of OX029 and test their efficacy in isolated blood vessels and cultured renal mesangial cells exposed to hyperglycemia. If OX029 is efficacious in preventing renal injury in STZ-diabetic rats, we plan to submit a Phase II grant to: (1) test one or two OX029 analogs for prevention of diabetic nephropathy in vivo, (2) expand the in vivo studies in STZ-diabetic rats to a long term study (6-9 months) to include other endpoints of renal pathology, such as histology and morphometry, glucose tolerance and insulin sensitivity, and renal function, and (3) expand the in vivo studies to include another animal model of diabetes, the db/db mouse which spontaneously develops type II diabetes. The long-term commercial goal is to develop an orally active drug which can be given to both type I and type II diabetics to attenuate the renal damage caused by chronic hyperglycemia, and also attenuate other vascular complications of diabetes.

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

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