Targeted formulations of GLP -1 for Type 1 diabetes

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$1,000,599.00
Award Year:
2004
Program:
SBIR
Phase:
Phase I
Contract:
1R43DK069727-01
Award Id:
71576
Agency Tracking Number:
DK069727
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
PHARMAIN, 650 BUCKTHORN TERR, BUFFALO GROVE, IL, 60089
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
ELIJAHBOLOTIN
(847) 947-0900
ebolotin@pharmain.com
Business Contact:
(847) 947-0900
Research Institute:
n/a
Abstract
DESCRIPTION (provided by applicant): New therapies are desperately needed for patients with Type 1 diabetes. Recent reports that the insulin-stimulating hormone Glucagon-Like Peptide (GLP-1), can increase pancreatic beta cell mass, offers the exciting prospect that beta cells can be regenerated in Type 1 diabetes, avoiding the need for islet transplantation. A number of modified analogues of GLP-1 are in development that are resistant to the peptidase DPP-IV that rapidly inactivates GLP-1 in the bloodstream. Our company proposes to apply a novel drug delivery nanotechnology Protected Graft Copolymers (PGC) coupled with Pharmaln's Reversible Binding (PRB) to reversibly associate native GLP-1 with the carrier. Since GLP-I in the carrier would be encased in a polymer; we anticipate protection of the peptide from cleavage by DPP-IV and thus an extended half-life. Importantly, since this carrier has been demonstrated to accumulate in sites of inflammation, the envisioned formulation would result in increased delivery to the pancreas, thus potentially minimizing gastrointestinal side effects. -to demonstrate the feasibility of the approach we propose to 1) formulate PGC/PRB:GLP-1 and measure the complex formation efficiency, binding constant and stability in serum; 2) determine the in vitro potency of PGC/PRB:GLP-1 receptor binding and sensitivity to degradation by DPP-IV ; 3) demonstrate the effect of PGC/PRB:GLP-1 on beta cell insulin secretion and glucose responsiveness as well as ability to induce neogenesis of new beta cells from ductal cells in vitro; 4) determine the PK, accumulation of the complex in the pancreas and its stability and 5) demonstrate efficacy in vivo in regeneration of beta cell mass in a rat model of streptozotocin-induced diabetes. The Phase II studies will involve the validation and optimization of the treatment to extended animal groups, including models of Type 1 diabetes in combination with immunosuppressants. The envisioned product, GLP-1 in an optimal pancreas-directed delivery system, should be of commercial interest not only for the treatment of Type 1 diabetes, but also for other applications being investigated for this peptide, including obesity, Alzheimer's and Type 2 diabetes.

* information listed above is at the time of submission.

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