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Urocortin-2 Gene Transfer for Type 1 Diabetes and Associated LV Dysfunction

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 4R42HL144299-02
Agency Tracking Number: R42HL144299
Amount: $1,598,215.00
Phase: Phase II
Program: STTR
Solicitation Topic Code: NHLBI
Solicitation Number: PA18-575
Timeline
Solicitation Year: 2018
Award Year: 2022
Award Start Date (Proposal Award Date): 2022-06-13
Award End Date (Contract End Date): 2024-06-12
Small Business Information
11455 EL CAMINO REAL
San Diego, CA 92130-2088
United States
DUNS: 032635352
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 HKIRK HAMMOND
 (858) 552-8585
 khammond@ucsd.edu
Business Contact
 JACK REICH
Phone: (858) 461-1837
Email: jack@renovatherapeutics.com
Research Institution
 VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
 
3350 LA JOLLA VILLAGE DR, 151A
SAN DIEGO, CA 92161-0002
United States

 Domestic Nonprofit Research Organization
Abstract

ABSTRACT
Type-1 Diabetes Mellitus (T1DM) affects 1.25 million patients in US with 40,000 new patients annually.
Lifespan is shortened 11-13 years, due to kidney and heart disease. Tight glucose control reduces
microvascular complications and adverse cardiovascular events. Insulin therapy is essential for such patients,
but has shortcomings: a) only 1 in 3 patients achieve targeted glucose control (HbA1c lt7%); b) aggressive
insulin therapy increases episodic hypoglycemia, which itself shortens life; c) most T1DM patients develop
insulin resistance. Cardiovascular risk is 2.5-fold higher in T1DM patients with insulin resistance vs those with
normal insulin resistance. We propose to test a new approach to address these shortcomings in T1DM
therapy. Recent clinical trials have tested non-insulin agents in combination with insulin in T1DM, to improve
glycemic control and reduce insulin requirements. In general, these trials show lower HbA1c and insulin needs,
but unacceptable side-effects. An ideal adjunct to insulin would: 1) reduce insulin needs and weight gain; 2)
reduce HbA1c; 3) require infrequent administration; and 4) favorably affect heart function. Our data in mice
indicate that urocortin 2 (UCn2) gene transfer fulfills these criteria in insulin resistant mice, and we recently
have discovered that UCn2 gene transfer normalizes glycemic control, reduces retinopathy, improves cardiac
function, and reduces mortality in a murine model of T1DM. We have shown the utility of intravenous delivery
of a vector encoding a transgene with paracrine actions that increases insulin sensitivity and release in
diabetes. This strategy enables patients to be treated during an office visit by a single injection of the vector. It
would eliminate the need for repeated administration, reduce costs and increase compliance. The best vector
to achieve these goals is adeno-associated virus type 8 (AAV8), encoding UCn2.The goals of this proposal are
to develop and optimally refine this approach to be used concomitantly with insulin in patients with T1DM.
T1DM is a major risk factor for several prevalent life-altering and life-terminating diseases that are the focus of
NHLBI: peripheral vascular disease, stroke, myocardial infarction, and heart failure. The discovery and
development of more effective therapies for T1DM is imperative, and is likely to reduce the prevalence of the
cardiovascular complications associated with T1DM. The goal of the current proposal is to test this new
approach.

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

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