Targets T1R3 (Taste receptor type 1 member 3), one of GPCR
G-protein-coupled receptors (GPCRs) that are expressed mainly in the brain have recently been adopted to regulate the neurodegeneration and cognitive dysfunction in AD as a potential therapeutic intervention.
Among various GPCRs, the Taste Receptors (TASRs for short) that mediate taste are expressed abundantly in the entorhinal cortex, are vulnerable to neurodegeneration, and have been found to be dysregulated in AD.
DIGMBIO, headquartered in Seongnam, South Korea, is a biotech venture developing the new GPCR-based therapeutics for AD. The company, in collaboration with Daegu Catholic University, is developing its novel DM3100 as a candidate molecule for the treatment of AD, which targets T1R3 (Taste receptor type 1 member 3, a component of TASR). DM3100 (the active ingredients of wheat bran Triticum aestivum extract) binds to and activates TASR, resulting in the release of neuroprotective peptides; glucagon-like peptide-1 (GLP-1), brain-derived neurotrophic factor (BDNF), and doublecortin (DCX).
In the preclinical studies, the wheat bran extract showed the neuroprotective and anti-dementia effects. It attenuated the cytotoxicity and apoptosis induced by the beta-amyloid in the SH-SY5Y human neuroblastoma cells and also restored the cognitive impairment in the triple transgenic animal models (3xTg AD mice). In a small randomized controlled trial with 70 elderly individuals who have subjective memory impairment, it improved visual memory.
The DM3100 project was selected as one of the preclinical studies for dementia treatment by the Korea Dementia Research Center in May 2021.
Meanwhile, the company is planning to initiate its phase 1 clinical trial of DM3100 for AD in 2023 after completing the preclinical studies by next year.
Choi E, Lee J, Park S, Jung E, Lim SH, Jang J, Chae S, Ko M. 2018. Wheat Bran Improves Cognition in Older Adults with Memory Impairment: A Randomized Controlled Trial. International Journal of Pharmacology. 2018;14:922-928.
Lee C, Park GH, Lee J, Jang J. (2015). Protective Effect of Wheat Bran Extract against β-Amyloid-induced Cell Death and Memory Impairment. The Korea Journal of Herbology. 2015;30(1):67–75.