Pilot and Feasibility Program Award Recipients

2012 Pilot and Feasibility Program award recipient

Awardee

Heidi J. Scrable, Ph.D., associate professor of biochemistry and molecular biology, College of Medicine, Mayo Clinic

Award period

Jan. 3, 2012, to Jan. 2, 2013

Project

Delta 40p53 and adaptive responses of stem cells to diabetic glucose toxicity

Purpose

The tumor suppressor p53 is a flexible stress sensor capable of molding a differential response to various kinds of environmental stressors, including genotoxic insults, reactive oxygen species and nutritional deficiencies. Dr. Scrable's team proposes to test the hypothesis that p53 can sense a toxic glucose environment that puts stem cells at risk of impaired function, proliferation, survival or differentiation.

This hypothesis is motivated by the discovery of an alternate isoform (delta 40p53) of p53 expressed exclusively in early embryogenesis and afterward only in stem cells that can modulate the activity of full‐length p53, adapting it to fit the peculiar circumstances of the early embryo and stem cell.

2011 Pilot and Feasibility Program award recipients

Awardee

Yasuhiro Ikeda, D.V.M., Ph.D., assistant professor of biochemistry and molecular biology, College of Medicine, Mayo Clinic

Award period

March 18, 2011, to March 17, 2012

Project

Pancreatic gene delivery for diabetes therapy

Purpose

Both major forms of diabetes involve beta cell destruction and dysfunction. Type 1 diabetes, which affects about 1 million Americans, is a condition of complete insulin deficiency brought about by autoimmune destruction of the insulin-producing islet beta cells. Type 2 diabetes affects about 20 million Americans. The hyperglycemia associated with type 2 diabetes develops when insulin secretory capacity can no longer compensate for peripheral insulin resistance.

Gene therapy is one approach to treat type 1 and 2 diabetes. Many genes have been identified to enhance beta cell development, neogenesis, regeneration or survival as strategies to repair defective function or to regenerate new pancreatic beta cells. Direct in vivo gene therapy for diabetes will likely require that therapeutic genes be delivered to pancreatic cells specifically and efficiently.

The overall goal of this project was to optimize the AAV vector-mediated pancreatic gene delivery system and to test the feasibility of this technology for hyperglycemia-reversing gene therapy in diabetic mouse models.

Awardee

Bijan J. Borah, Ph.D., assistant professor of health services research, College of Medicine, Mayo Clinic

Award period

March 18, 2011, to March 17, 2012

Project

Real-world evidence on the comparative effectiveness of lipid management strategies in type 2 diabetes mellitus

Purpose

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial has shown that compared with simvastatin monotherapy, combination therapy of simvastatin plus fenofibrate doesn't reduce the rate of cardiovascular disease events in type 2 diabetes patients. While the ACCORD Lipid trial addressed the long-standing question about the efficacy of statin fibrate combination therapy for managing cardiovascular disease risks in type 2 diabetes patients, it remains to be documented whether the publication of the ACCORD study results has had any impact on real-world clinical practice.

Given that the ACCORD trial reflected on the clinical practice setting only partially, and that it left unresolved the question of effectiveness of non-ACCORD statin monotherapies and statin fibrate combination therapies, there is clearly a need to understand the real-world practice patterns for the management of dyslipidemia-induced cardiovascular disease risk in type 2 diabetes patients with elevated risks of cardiovascular disease events.

Because of this, two specific aims were pursued:

  1. Assessing prevalence of statin monotherapies and statin-plus-fibrate combination therapies in type 2 diabetes patients with elevated cardiovascular risk pre- and post-publication of the ACCORD study results
  2. Comparing primary and secondary outcomes between statin monotherapy cohorts and statin-plus-fibrate combination therapy cohorts:
    • The primary endpoint included the first occurrence of nonfatal myocardial infarction, stroke or cardiovascular death
    • Secondary outcomes included expanded macrovascular outcome (any of the primary endpoints plus any revascularization plus hospitalization for heart failure), all-cause mortality, cardiovascular mortality, major coronary artery disease events, total stroke, and congestive health failure death.