# Development of CB1 Monoclonal Antibodies for Treating NASH

> **NIH NIH R44** · INTEGRAL MOLECULAR · 2020 · $339,478

## Abstract

ABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is the accumulation of intra-hepatic lipids within
hepatocellular lipid droplets, or “hepatic steatosis”. Hepatic steatosis can progress to
nonalcoholic steatohepatitis (NASH), a chronic inflammatory condition that can lead to liver
fibrosis and cirrhosis. Underlying factors associated with the development of NAFLD/NASH
include obesity and hyperlipidemia. NASH currently affects over 10 million people in the U.S.
and is becoming the primary cause of liver failure and transplant, with no approved medical
therapies. The cannabinoid receptor CB1 is a validated target for treating NASH and obesity. As
a G protein-coupled receptor (GPCR), CB1 regulates metabolic pathways and appetite through
the natural endocannabinoid system, and is also the primary mediator for the effects of THC in
marijuana. CB1 is highly expressed in the liver and other peripheral tissues, where it regulates
metabolism independent of its effects on the brain. Small-molecule inhibitors of CB1 have been
well studied and even clinically approved (rimonabant). However, nearly all have been
withdrawn from the market and clinical development due to their central nervous system-
mediated adverse psychoactive effects. Drugs that can de-couple the peripheral (metabolic)
effects of CB1 from its central (psychoactive) effects, such as MAbs that naturally do not cross
the blood-brain barrier, are predicted to be highly effective in treating NASH, obesity, and their
associated complications. However, inhibitory MAbs against GPCRs such as CB1 are extremely
challenging to isolate because GPCRs are hydrophobic, form complex transmembrane
structures, and are difficult to purify away from their native lipid environment. Here we propose
to develop MAbs targeting the GPCR CB1 for the treatment of NASH.

## Key facts

- **NIH application ID:** 9918931
- **Project number:** 5R44DK117803-04
- **Recipient organization:** INTEGRAL MOLECULAR
- **Principal Investigator:** Benjamin J Doranz
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $339,478
- **Award type:** 5
- **Project period:** 2018-09-07 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9918931

## Citation

> US National Institutes of Health, RePORTER application 9918931, Development of CB1 Monoclonal Antibodies for Treating NASH (5R44DK117803-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9918931. Licensed CC0.

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