Gene Therapy for Type 1 Diabetes

TypeDiabetes MellitusT DMis an increasingly prevalent form of diabetes in which the insulin producingcells of the pancreas are destroyed by an autoimmune attackand as a resultno endogenous insulin is producedMost often diagnosed in childrenmillion Americans suffer from T DMandnew cases are diagnosed annually worldwideT DM profoundly impacts patientshealth and quality of life due to the constant need to measure blood glucose levelsto normalize those levels with insulin injectionsand to strictly adhere to special dietary requirementsEven with these methodsmany diabetics achieve only erratic or limited control over their blood glucose levelsAs a resultfluctuations in blood glucose levels occurleading to complications such as end stage renal failureblindnessand non traumatic amputationsGiven the quality of life and health consequences suffered by millions of T DM patientsnew and effective treatments remain an urgentunmet needEndsulinIncMadisonWIproposes to develop a treatment for T DM based on an insulin expression transgene therapy that is expected to result in glucose dependent insulin secretion from the liver of T DM patientsThe treatment will be noninvasiverequiring a single intravenous injectionand should control blood glucose levels in patients with T DM while preventing or minimizing secondary diabetic complicationsPreliminary studies conducted at the University of Wisconsin Madison and the University of Pennsylvania have shown that a novel gene therapy construct consisting of a destabilized human insulin mRNA expressed under the control of a glucose responsive promoter can restore glycemic control in a rodent model of T DM without inducing post prandial hypoglycemiawhich has been a limitation of earlier attempts at the use of insulin gene therapy constructsIn this Phase I STTREndsulin will work cooperatively with the University of Wisconsin to demonstrate the feasibility of this gene therapy approachIn Aimthe therapeutic dose of the gene therapy constructdelivered using adeno associated viruswill be optimized in streptozotocin treated micea well accepted model of T DMIn Aimthe therapeutic dose will be optimized in experimental diabetic dogsand the long term safety and efficacy of the therapy will be determinedIn the planned Phase II studiesEndsulin intends to conduct long termyearpreclinical studies on spontaneously diabetic companion dogsto be followed with FDAIND approval and human trialsWith this innovationT DM patients may no longer need to test their blood glucose levels or inject themselves with insulin multiple times each dayAside from the enormous health and lifestyle benefitsthe T DM gene therapy approach developed here should dramatically reduce the economic costs of this increasingly common condition People with typediabetes cannot control their blood sugar because their bodies no longer make insulinEven when patients measure their blood sugar many times a day and give themselves insulin injectionsthey often suffer from complications of their diabetesThis project will develop a new diabetes therapy that will make the patient s body able to produce insulin again after only one injection so they will not need daily insulin injections anymore