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Please Note: The technology listed below is not available to the public at this time. This technology is in the early stage of research and requires further development before it is ready for the marketplace. The VA is currently in the process of identifying potential companies who may be interested in licensing and/or further developing the technology through Cooperative Research and Development Agreements (CRADA). Through cooperative research initiatives such as these, it is our hope and goal that commercial products will be fully developed and made available to benefit veterans and others.
VA TECHNOLOGY OPPORTUNITY BRIEF
Glucose Sensitive Regulator of Insulin Transcription
(99-003)
OPPORTUNITY:
The Department of Veterans Affairs (VA) is seeking a commercial partner through a Cooperative Research & Development Agreement (CRADA) to further develop a set of insulin regulator nucleic acid constructs designed to deliver insulin in a subject with type 1 insulin-dependent diabetes in a manner responsive to glucose levels.TECHNOLOGY OVERVIEW:
Insulin-dependent diabetes mellitus (type 1) is an immune-mediated disease associated with the loss of pancreatic beta cells resulting in insulin dependence for life. Patients with type 1 diabetes require long-term medical treatment and experience a life-long struggle to control their blood glucose levels in order to limit the development of complications and manage and treat complications when they occur. Type 2 diabetes, formerly called non-insulin dependent diabetes, produces abnormal carbohydrate, lipid and protein metabolism associated with insulin resistance and impaired insulin secretion. Unmanaged diabetes can result in many potential complications, including hypoglycemia or hyperglycemia, infections, microvascular disease, neuropathy and blindness.The current treatment for managing glucose levels in patients with type 1 diabetes involves therapeutic use of insulin delivered via external devices such as insulin pumps or pens. Type 2 diabetes is controlled either by combining two or more oral agents or by insulin therapy if the oral agents fail to provide adequate glycemic control. Unfortunately, the risk of hypoglycemia limits the effectiveness of insulin therapies, so there is a need for new treatments that provide better control of glucose levels with less risk of hypoglycemia.
The inventor of the subject technology determined that type 1 diabetes is a natural candidate for gene-based therapy because decreased production of a single protein is responsible for the clinical symptoms of the disease. The subject technology is a set of insulin regulator nucleic acid constructs designed to deliver insulin in a subject with type 1 diabetes in a manner responsive to glucose levels. The key features of the nucleic acid construct are glucose responsive elements (GIREs) and an insulin sensitive element that confer two important properties for transgenic production of insulin-stimulation by glucose and inhibition by insulin. The subject technology also includes vectors comprising the insulin regulator constructs, pharmaceutical compositions comprising the insulin regulator construct and methods of treating or preventing diabetic conditions in a subject.
TECHNICAL MERIT:
The subject technology constructs, which may prove useful in gene therapy to treat type 1 diabetes, appear to represent an important technological advance. The promoter constructs that are responsible for expressing the gene have undergone initial testing in rats, which are a good model for the human disease. Experiments have shown that the promoter is stimulated by glucose and inhibited by insulin. Further, the stimulation by glucose is dose dependent. The promoter functions sufficiently well in the animal model and within an acceptable time frame to prevent the rats from developing symptoms of the disease.POTENTIAL APPLICATION:
The primary application of the subject technology is the treatment of type 1 diabetes. In addition, the subject technology might also be useful for treating insulin-dependent patients with type 2 diabetes.PATENT STATUS:
A US provisional application was filed on October 11, 2000 (60/239,113)
A U.S. patent application was filed on October 10, 2001 (09/972,916).
Federal Register: Mar. 6, 2002 (Vol.67, No. 44) p.10259FOR MORE INFORMATION CONTACT:
Saleem Sheredos
Program Manager
Technology Transfer Program
Veterans Affairs
Office of Research & Development (12TT)
5th Floor
103 South Gay Street
Baltimore, MD 21202
202-380-5080
Fax 410.962.2141
e-mail: saleem.sheredos@va.gov