Times of India
07 September 2011
India, Mumbai

Breakthrough in Alzheimer’s Research
Dr Sudipta Maiti’s paper, published in an international science journal, has created a buzz in medical circles
AMumbai–based scientist's path–breaking research on rogue protiens in human brain that cause Alzheimer's has brought new hope in the global quest for finding a treatment for the degenerative disorder previously thought to be incurable.

Dr Sudipta Maiti, a professor at the Department of Chemical Sciences, TATA Institute of Fundamental Research (TIFR), and his team have found that it is possible to reverse the behaviour of Amyloid Beta protiens that cause Alzheimer's when they depart from their prescribed function of aiding human memory and cognitive behaviour. These renegades join hands with other similarly misbehaving protiens, and together they attack brain cells impairing speech, judgement, memory, perception and behaviour. Dr Maiti's research showed that when these gangs of bad–boy Amyloid Beta protiens are separated from each other, they return to their original form and resume originally prescribed functions, mainly related to aiding human memory and cognitive behaviour.

So far it was believed that the Amyloid Beta oligomers – science jargon for gangs of bad–boy protiens – were a stable bunch and did not return to their normal state. With Dr Maiti's research, this thinking is bound to change.

Alzheimer's Disease International, a federation of nonprofit organisations promoting awareness about the disease, has estimated that as of 2010, there were 35.6 million people with dementia worldwide. By 2050, it is projected that this figure will have increased to over 115 million. Since Alzheimer's is an old–age disease and India's life expectancy has been rising rapidly, one is likely to hear more about it in the coming years.

Dr Maiti's team demonstrated the mob mentality of Amyloid Beta protiens gone bad by creating Alzheimer's disease in a test tube. They placed monomers (single units) of Amyloid Beta in a waterbased solution at a normal concentration of 100 nm (nanomolar), mimicking the human brain fluid (cerebro spinal fluid). "When we increased the concentration of the fluid above normal, we observed that the Amyloid Beta protein started forming oligomers (multiple units). These oligomers, together, were toxic enough to cause Alzheimer's," he said.

However, when the concentration of artificial brain fluid was lowered to normal again, Amyloid Beta oligomers split back into individual units, lost their toxicity and, in fact, returned to performing their original assigned tasks. "We were able to reverse the Alzheimer's disease in the test tube. We discovered that after seven days of lowering the concentration of the brain fluid, the oligomers became unstable and broke out from the group to form harmless monomers of the protein found in healthy brains," Maiti said.

All forms of proteins in the human body take a particular shape to perform their prescribed functions. Let's say, for instance, that the Amyloid Beta protein is supposed to fold into the shape of a 'boat' to facilitate a certain brain function. In Alzheimer's, the protein, for reasons not yet known, starts folding into the shape of a 'frog' after it has folded into a 'boat'.

This misfolded protein becomes toxic to the brain when it forms associations with other misfolded proteins. "In a healthy brain the protein is supposed to exist as a monomer. The misfolded protein forms structures of oligomers (two, three or four proteins) and starts killing the brain cells," Maiti added.

As a cleansing process the human body keeps eliminating the dead cells. Because brain cells are not known to replenish, it leads to extreme shrinkage of the brain and dementia.

The implication of the research, which has appeared in the Journal of Biological Chemistry published by the renowned American Society of Biochemistry and Molecular Biology, is that it will be possible now to target the oligomers in the brain fluid with the development of a specific drug which will break their bond. "The task at hand is to find a way to replicate the test–tube process inside the brain. We know what to do but we don't know how to do it. We still have not discovered the pockets in human brain where oligomers form. Finding them and developing a method by which we can assess the population of the oligomers, will make it easy to target them with a drug. We have started working towards the next step."

City's top doctors said the research is an important step, but much needs to be done before it translates into a cure for Alzheimer's. Dr P P Ashok, head of neurology at Hinduja Hospital, said Dr Maiti's research is like a drop in the ocean. "Since every drop counts, I do not discount the credibility of this research. We will have to wait and watch its implication."

Dr Ashok M Sirsat, neurologist, Lilavati Hospital, said the research is a step in the right direction. "It will certainly be helpful in the long run. But in day–to–day practice Alzheimer's is difficult to detect twenty years before its progress. By the time it's detected, it's already too late for the patient," he said.

Dr Roop Gursahani, consulting neurologist, Hinduja Hospital, said the research is good in its place and context. However, translating it from a test tube to actual medication would be a huge challenge. "First we have to develop a drug, then a treatment, then test it on a patient and then see if results are achieved," he added.

As you read this, Dr Maiti and his team are probably working on just that.
The Breakthrough
So far it was believed that the Amyloid Beta oligomers – science jargon for gangs of bad–boy protiens – were a stable bunch and did not return to their normal state. With Dr Maiti's research, this thinking is bound to change.