Joint research by Korea Brain Research Institute and Yonsei University confirms Alzheimer's-improving effects of insulin receptor inhibitor

Alzheimer's disease. [Getty Images Bank]
Alzheimer's disease. [Getty Images Bank]

South Korea has approximately 1 million dementia patients, and the annual cost of managing dementia patients aged 65 and older stands at 20.8 trillion won (about $13.7 billion).

Often called "the cruelest punishment bestowed by God," dementia gradually strips away human memory — and effective treatments remain elusive. Only a handful of dementia drugs have received approval from the US Food and Drug Administration, and none offers a fundamental cure.

South Korean researchers have now published findings showing that an insulin receptor inhibitor can be effective in treating Alzheimer's disease.

The Korea Brain Research Institute (KBRI) announced Thursday that a joint research team — led by Director Heo Hyang-sook at KBRI and Professor Seo Jin-su of Yonsei University — has identified the mechanism by which the insulin receptor inhibitor BMS-754807 simultaneously regulates key Alzheimer's disease pathology and neuroinflammation.

Alzheimer's disease arises from a complex interplay of chronic neuroinflammation, amyloid beta accumulation and tau protein mutations. The research team demonstrated that BMS-754807, a compound that modulates insulin-like growth factor-1 receptor (IGF-1R), is highly effective at suppressing inflammatory responses in the brain and restoring synaptic function.

A schematic diagram showing the mechanism by which the insulin receptor inhibitor improves Alzheimer's disease pathology. [Provided by Korea Brain Research Institute]
A schematic diagram showing the mechanism by which the insulin receptor inhibitor improves Alzheimer's disease pathology. [Provided by Korea Brain Research Institute]

The joint research team administered the compound to cell models derived from human induced pluripotent stem cells (hiPSC) and to Alzheimer's animal models (5xFAD and PS19). The team confirmed that production of inflammatory cytokines was suppressed and that hyperactivation of microglia and astrocytes was brought under control. The researchers also observed significant reductions in amyloid plaque accumulation and tau protein hyperphosphorylation — two hallmarks of dementia — along with measurable improvements in cognitive function.

The joint research team from the Korea Brain Research Institute and Yonsei University. [Provided by Korea Brain Research Institute]
The joint research team from the Korea Brain Research Institute and Yonsei University. [Provided by Korea Brain Research Institute]

"These findings suggest the possibility of drug repurposing for existing insulin receptor inhibitor candidates," said Heo Hyang-sook, director of the research team. "Building on the mechanisms we have identified, we plan to contribute to the development of future treatment strategies for neurological diseases."

Professor Seo Jin-su added, "Having confirmed consistent effects in both human-derived cell models and animal models, these results will serve as important evidence supporting the clinical applicability of this approach as an Alzheimer's treatment strategy."

The findings were published in the latest issue of the Journal of Neuroinflammation, an international academic journal in the field of brain science.


nbgkoo@heraldcorp.com