Preeti Mehra

Alzheimer’s disease is a major health concern among India’s ageing population. According to the Dementia in India 2020 report, an estimated 53 lakh persons above the age of 60 suffer from one form of dementia or the other, with Alzheimer’s being the most common of these. In simple terms, one in 27 of our senior citizens is afflicted by a chronic disorder of their mental processes, resulting in impaired memory, reasoning, and personality changes.

Now, there is hope in the form of groundbreaking discoveries by Prof T Govindraju of the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bengaluru. It holds potential for the diagnosis and treatment of Alzheimer’s as well as lung cancer. Govindraju was awarded the Shanti Swarup Bhatnagar Prize for Science and Technology 2021 for his innovations and discoveries.

The ‘drug candidate’ molecule — TGR63 — has been designed and synthesised at the JNCASR laboratory after 10 years of effort. Once put through human clinical trials, it promises to be the treatment protocol for Alzheimer’s. A drug candidate molecule is one which has medicine-like properties and is qualified for further development and clinical trials in humans.

As Govindraju explains, Alzheimer’s disease is a progressive neurodegenerative disorder caused by the clumping of proteins into toxic aggregates (amyloids), leading to cognitive decline and impairment in learning, memory, and behaviour in general.

TGR63 prevents the clumping of proteins into toxic amyloid (a waxy translucent substance consisting primarily of protein deposited in animal organs and tissues under abnormal conditions such as Alzheimer’s disease). The molecule dissolves the amyloids into a soluble, non-toxic form. This reduces amyloid toxicity. It is the clumping together of amyloids that forms plaques between neurons and disrupts brain cell function.

TGR63, Govindraju says, can be formulated into tablets or as an injection, which can be decided during clinical studies by the pharma company. Govindraju’s work has also led to the development of molecular tools to detect Alzheimer’s disease and differentiate it from other neurological disorders. Early detection, he says, is crucial to treat and manage Alzheimer’s. The tools have been patented by JNCASR and the patents are being transferred to VNIR Biotechnologies Pvt Ltd, a deep science start-up from JNCASR with expertise in bioimaging and diagnostics.

Targeting lung cancer

Another drug candidate molecule discovered while studying the relationship between Alzheimer’s and cancer — TGP18 — could serve as a diagnostic tool for lung cancer. TGP18 has shown excellent efficacy against lung cancer, a difficult cancer type to detect and treat. “TGP18 can be used to detect or track the treatment course through its light-up fluorescence signal, with potential for diagnosis and therapy,” notes Govindraju.

Functional amyloids derived from silk to treat Alzheimer’s are also under development at JNCASR. Govindraju notes that silk is an edible natural protein which degrades easily over time. “We developed a silk formulation in which stem cells can differentiate (transform) to neuronal cells,” he says.

Currently, when a patient is diagnosed with Alzheimer’s, he or she has already lost a large number of neuronal cells. While drug and/or treatment can give neuroprotection for existing neurons, substituting the lost neurons also makes for a viable treatment strategy. In this context, introducing silk-supported stem cells in the brain will lead to neuronal trans-differentiation and substitution for lost neurons.

This, however, is still at an early stage of development.