Use of DYRK1A/b kinase inhibitors for the treatment of liver diseases
Ended Project Grant Awarded Last action
- Award ID
- R43DK134232
- Recipient
-
Avanti Biosciences, Inc. UEI GZNJSM9ELXB3
- Awarding agency
-
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $349,235
Award facts
- Assistance listing
- 93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research
- Completion date
- Originally
- Place of performance
- California, USA
Award details come from USAspending.gov.
Description
- Abstract
- Nonalcoholic fatty liver disease (nafld) is the most prevalent chronic liver disease. One-fourth of the adult population suffers from nafld worldwide. Nonalcoholic steatohepatitis (nash), the aggressive form of nafld, can progress to cirrhosis and hepatocellular cancer (HCC) and is rapidly becoming the leading cause of end-stage liver disease and liver transplantation. Liver fibrosis is a major consequence of chronic liver disease, where the excess extracellular matrix is deposited, which is caused by the activation of hepatic stellate cells (hscs). There is an urgent public health need to develop safe and effective pharmacological treatments to alleviate hepatic inflammation, fibrosis, and steatohepatitis. However, there are no FDA-approved medications for nafld. This sbir phase i proposal seeks to evaluate ABI-171, a novel compound with demonstrated selectivity for DYRK1A and its close family member DYRK1B in biochemical and cellular assays. ABI-171 exhibits pharmacological activity with evidence of efficacy in several animal models of disease. We hypothesize that its broad anti-inflammatory and cytoprotective activities combined with its potential health-promoting activities to thwart diabetes, reduce fatty acid uptake, and suppress collagen accumulation may effectively combat nafld. In this phase i study, two specific aims are proposed: in aim 1 we will evaluate the accumulation of ABI-171 in the organs of interest, namely the liver, to advance its safety profile. In aim 2, we will test the efficacy of ABI-171 in the high-FAT diet model of nash, which is well-established for providing mechanistic insight of treatments and its potential for research translation. Detailed readouts for this study will be bodyweight and food intake, insulin resistance, liver injury biomarkers, liver pathology including histological and biochemical assessments, and expression levels of genes and proteins involved in DYRK1A/1B-mediated regulation of cellular cytoprotection, inflammation, lipogenesis, and fibrogenesis. The successful completion of this application will significantly advance the efficacy and mechanism of action of our selective dyrk inhibitor in nash, thus forming strong foundation for a phase 2 project in which drug activity will be examined in more detail for the treatment of metabolic disorders and complete the development work needed to move ABI- 171 into an early-stage clinical trial.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Original award | $349,235 |
Quick answers
Who received award R43DK134232?
R43DK134232 was awarded to Avanti Biosciences, Inc. by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on August 1, 2023.
How much is award R43DK134232 worth?
$349,235 has been obligated on R43DK134232.
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