Old drug, new prescription

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By A drug may finally be in the offing for Japanese encephalitis, if a Calcutta-born scientist's work passes through clinical trials. T.V. Jayan reports
  • Published 14.03.11

Come April and neuroscientist Anirban Basu will have every reason to be elated. And anxious too. That’s when a drug the National Brain Research Centre (NBRC), Manesar, Haryana, researcher has repurposed for an incurable brain fever is scheduled to go for clinical trials.

The drug minocycline has been around for some time. A second-generation antibiotic, it’s used for treating pimples and other skin infections. In 2008, Basu and his students showed it might be effective against Japanese encephalitis (JE), a mosquito-borne viral disease that affects the brain. They showed that it protected mice infected by JE virus from death.

Whether the drug will be equally promising in humans will be known when a team of medical doctors from the CSM Medical University, Lucknow, conducts clinical trials. Currently, there’s no specific treatment for JE and it is all left to the body’s immunity to fight the virus. There are vaccines but of limited supply. They are only of 60 per cent efficacy as well as expensive.

The JE virus — that belongs to the flavivirus family — kills up to 15,000 people, mostly children, every year in India and many Southeast Asian countries. In India, it is more prevalent in eastern Uttar Pradesh and parts of southern India.

“If I were to return to India, I would work on problems that affect our people, particularly the neglected diseases,” says Basu, who hails from Calcutta. It’s a major shift in focus for him as he had earlier worked on manifestations of progressive degenerative disorders such as multiple sclerosis, which mainly afflict populations in rich nations, as a postdoctoral researcher at Pennsylvania State University College of Medicine, the US. Basu joined the faculty at NBRC in 2004, accepting an offer from the then director, Vijayalakshmi Ravindranath.

Basu has also unravelled how smoking leads to the destruction of brain cells. He found that when certain chemicals found in tobacco reach the brain, they may trigger a chain reaction leading to neuron damage. Besides, his team is trying to understand how environmental pollutants and heavy metals affect the brain.

“I always wanted to pursue a career in scientific research,” says the NBRC researcher, who attended Vishwa Bharati University, Shantiniketan, for higher studies and did his doctorate from the Indian Institute of Chemical Biology, Calcutta, before leaving for the US in 1998.

His banker parents, particularly his mother — his father passed away when he was in school — were happy with his choice. “Even today a large number of people in Bengal and southern India attach a lot of value to science education,” says Basu, who like most Bengalis loves soccer. When he isn’t busy in the lab, he is reading books by Bengali novelists Buddhadeb Guha or Amitav Ghosh.

The immediate provocation for Basu to take up JE as a research challenge was an epidemic of the viral encephalitis in eastern UP in 2005 that killed more than 1,300 children below 15. “This occurred around the time I was settling into my new position at NBRC,” he says.

JE, which damages the brain and spinal cord, is particularly lethal in children, as older people have greater immunity. The mortality is high, with one in three affected children dying.

This prompted him to look into the molecular mechanisms that go on inside a JE-infected brain. His studies of lab mice showed that following the infection, microglia — resident scavenger cells in the brain — get activated. In addition to cleaning up debris of the neurons killed by the virus, the microglial cells attack healthy neurons critical for normal brain function. “It’s quite like a good strategy that has backfired,” says Basu.

Subsequent studies threw more light on the problem. His team found that apart from the destruction of brain cells, the infection deactivates a resilient mechanism of repair that the brain resorts to when similar infections occur. The JE virus prevents neural stem and progenitor cells in the brain from dividing. This explains why many survivors of the diseases have compromised mental functions in later life.

“The work provides a scientific basis for trying minocycline on JE. This is a new indication for the drug, very different from its conventional use as an antibiotic,” says NBRC director Subrata Sinha. If the clinical trials yield positive results, this off-patent medicine may provide an efficacious and inexpensive way of ameliorating the disease, he adds. The scientists have already received approval from the drug controller general of India to conduct the trials.

“The clinical trials with minocycline are scheduled to begin in April. While 72 volunteers will receive minocycline, an equal number of people will be put on a placebo,” says Rashmi Kumar, a paediatrician heading the team.