The Chasing Iamb

A story I got thanks to the lovely Vineet Surendranath.

WHEN FANTASY author Terry Pratchett recently announced that he had been diagnosed with early onset of Alzheimer’s disease, he said, “I know it’s a very human thing to say ‘Is there anything I can do,’ but in this case I would only entertain offers from very high-end experts in brain chemistry.” Though Alzheimer’s disease (AD)
Insight Rajendran at the Max Planck Institute in Germany

affects 5% of the population above the age of 60 in India, popular culture has done it little service until the recent Kajol-starrer You, Me Aur Hum. It continues to be misunderstood, and confused with beasts of a similar marking such as senile dementia, amnesia or even plain absent-mindedness. Support groups in India are few and trained caregivers are located only in major cities. So it is unsurprising that there has not been greater excitement in India that 33-yearold Lawrence Rajendran, a cell-biologist in Germany, is the lead author of a recent paper published in Science that points to a simple and brilliant new direction for AD drugs.

Rajendran has been working for the past five years at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany. He studied at the University of Madras and the Indian Institute of Science, Bangalore, and joined Max Planck for his postdoctorate. He is a senior scientist with Dr Kai Simon’s group whose research recently led to a radical breakthrough in Alzheimer’s research. Rajendran’s fundamental innovation has been this: beta-secretease is the key enzyme that produces a plaque-like substance in brain cells. These deposits damage the brain cells, leading to symptoms of Alzheimer’s, beginning with forgetfulness and ending with dementia and the loss of major bodily functions.

So far, drugs have attempted to inhibit this enzyme, as if sealing a house containing poisonous gases. Rajendran had earlier established that only a particular compartment within cells (endosomes) provide the right environment for the enzyme to work. This key discovery led to the next stage. Here, Rajendran and colleagues successfully attempted the equivalent of going into the house, finding the room from which the poisonous gases emanate and finding the right way to stem the leak.

The team devised a way to anchor the drug to the cell membrane to stop the harmful deposits. They also seem to have targeted specialised domains called rafts (a membrane feature thought to be critical for HIV entry and allergies). “Our research is proof-of-principle for an approach that could be crucial for treating other diseases such as Ebola and AIDS. It is like hitchhiking into the cell: we use cellular strategies to deliver the inhibitors to the exact site where they are needed,” says Rajendran. He adds with some amusement, “It seems incredibly obvious now, almost the common sense approach. Someone should have thought of it before us.”

Rajendran suggests that one of the reasons his team was able to work on alternative approaches is because they exist in an academic setting, working out of a publicly-funded institution, unlike those limited by the pragmatic funding of corporate research. “Our work is also proof that you can do good work in academia without starving,” he says. “Academic labs can also contribute to drug discovery and the concept of the lab as an entrepreneurial entity is something to think about.”

Rajendran’s mentor Kai Simons is the founder of JADO Technologies (pronounced jadoo, as in magic), a spin-off from the Max Planck Institute that will conduct the three years of animal testing and possible decade of human testing to assess the drug for side-effects and toxicity. In the fiercely competitive world of pharmaceutical research, the international market for AD drugs is already valued at $3.8 billion and this for drugs that only reduce the severity of its symptoms but cannot halt AD’s violent progress. If successful, JADO may be the surprise winner in a high-stakes game. It would also provide relief to those anxious that a sudden inability to remember a name may be the first sign of a life of misery.