New molecule could be potential drug candidate to halt or cure Alzheimer’s

BENGALURU: After more than 10 years of research, scientists from Jawaharlal Nehru Centre for Advanced Scientific Research have developed a small molecule that can prevent the mechanism resulting in neurons (brain cells) becoming dysfunctional in Alzheimer’s disease (AD).


The team led by professor T

Govindaraju

is confident that the molecule, christened TGR63, could be a potential drug candidate to halt or cure the leading cause of dementia. “We are preparing for clinical trials and are looking to partner with pharma firms both in India and outside,” Govindaraju told TOI.

Stating that in the Alzheimer’s brain, abnormal levels of naturally forming protein clump together to form plaques that collect between neurons and disrupt cell function, Govindaraju said this is caused by production and deposition of a protein called

amyloid peptide

that accumulates in the central nervous system.

“The multifactorial nature of AD, attributed to multifaceted amyloid toxicity, has kept researchers from developing effective treatment. Now, we have designed and synthesised a set of novel small molecules and identified a lead candidate which could reduce amyloid peptide toxicity,” he explained. He said detailed studies have established TGR63 to rescue neuronal cells from amyloid toxicity. Remarkably, he said, the molecule was also found to reduce amyloid burden in the cortex and hippocampus, or a complex part embedded deep into the temporal lobe, thereby reversing cognitive decline. This research was recently published in the journal Advanced Therapeutics.

“Any treatment relating to the brain has a major challenge in breaking the blood-brain barrier which prevents drugs from reaching the brain. In this case, TGR63 manages to break this and enter the brain,” he said.

Govindaraju added there are no approved drugs that directly act on disease mechanisms of AD. He said while the incidence, and especially deaths due to most major diseases like cancer, are on the decline globally, AD has registered increase of 71%. Thus, there is a need to develop drug candidates to halt or cure Alzheimer’s.

“During our studies, mice brains affected with AD when treated with TGR63 showed a reduction of amyloid deposits, validating its therapeutic efficacy. The mice also showed reduction of learning deficiency and memory impairment as revealed by distinct behavioural tests...,” he said.