A dual-acting small molecule for the treatment of type 1 diabetes

Ended Project Grant Awarded Last action

Award ID
R41DK131839
Recipient
Awarding agency
Obligated
$899,922

Award facts

Completion date
Originally
Funding
  • $599,948.00 Federal
  • $299,974.00 Non-federal
Place of performance
Athens, OH 45701, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Over 1.5 million americans suffer from type 1 diabetes, an autoimmune disorder involving insulin, an essential hormone to blood glucose regulation and overall energy metabolism. When first diagnosed with T1D, IT is estimated that the patient's insulin secreting capacity has been reduced by 70-90%. By this point, the immune system has already targeted and destroyed a vast majority of insulin-producing pancreatic beta cells, in large part, through a barrage of pro-inflammatory cytokines triggering cell death. For a century since its discovery, there have not been any other substantial therapeutic advancements outside of insulin to treat T1D. However, recent therapeutic advancements targeting beta-cell health have resulted in several clinical trials. Asake biotech, in collaboration with investigators at ohio university, is developing a small molecule therapeutic that both maintains islet health and enhances insulin secretory capacity to treat two key issues in T1D. In tests of rodent and human pancreatic islets in a dish, our lead compound MSB-3 protected beta-cells from cytokine-induced cell death and stimulated these cells to produce and secrete more insulin without depleting insulin reserves. Preliminary data in non-obese diabetic (NOD) mice, a mouse model of T1D, with established diabetes (blood glucose >400 MG/DL) show that daily MSB-3 treatment stabilizes blood glucose, increases serum c-peptide levels (a marker for insulin production), and decreases pancreatic insulitis (a sign of reduced autoimmunity). This dual action appears to be unique among potential diabetes therapies. However, we have yet to optimize our current lead for potency and safety or to test preclinically for potential next-step trials. Our overarching goal is to use MSB-3 as a starting point for further development of a small molecule with dual activity for the treatment of T1D. Our first specific aim is to thoroughly test MSB-3 for toxicity, protection from cytokine-induced cell death, and estimated pharmacokinetics using liver microsomes. Our second aim is to test MSB-3 in a preclinical mouse model of T1D (non-obese diabetic mice) to determine if our lead compound can prevent or even reverse existing T1D. If successful, these studies will provide insight into potential overlapping pathways between insulin secretion and cell protection. This work will also provide crucial data needed to accrue additional support to further develop this potentially novel and unique treatment of diabetes.

Transactions

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Quick answers

Who received award R41DK131839?

R41DK131839 was awarded to Asake Biotechnology, LLC by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on September 20, 2021.

How much is award R41DK131839 worth?

$899,922 has been obligated on R41DK131839: $599,948 in federal funding and $299,974 in non-federal funding.

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