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Getting help from herpes

LiveMint logoLiveMint 12-06-2014 Samar Halarnkar

The ancient Greeks gave the virus its name. A Roman Emperor once banned kissing to stop its spread. A line in Romeo and Juliet indicates that even Shakespeare was familiar with the herpes virus and the irksome lesions it causes.

Now, a Kashmiri scientist at the Harvard Medical School has turned this old viral foe of humanity into a potential weapon against one of its deadliest medical conditions: cancerous tumours in the brain. Khalid Shah, 43, an associate professor, and his colleagues recently demonstrated how cancer-killing, or oncolytic, herpes viruses could be loaded onto human master cells, called stem cells, immersed in a gel that helps it stay alive and be applied directly to the most common human brain tumours, glioblastoma multiforme, which are fatal in almost every case.

In a study published last month in the Journal of the National Cancer Institute in the US, human stem cells loaded with the herpes virus greatly cut the death rate in tumours grown in mice. Human, or clinical, trials could start in two to three years.

Currently, treatment focuses on resecting, or cutting away, part of the tumour, followed by chemotherapy and radiation. But if even some cancerous cells survive, as they almost always do, the cancer comes flooding back. In the mice experiments, the herpes virus tended to mop up these residual cancer cells.

“The herpes virus is a really potent killer,” Shah, also director of the Stem Cell Therapeutics and Imaging Program at the Massachusetts General Hospital in Boston, told me. “Current survival for brain tumours is 15 months from detection. It could immediately go to three or four years.” The technique that Shah and his team demonstrated could potentially also be used on other tumours.

In the course of a meeting at his office, Shah explained his intention is to help a “mass of patients, rather than a few elite”. He said: “I am really keen to do this in India.”

Shah, who confessed to “learning very little nothing” while at college in Srinagar during the violent, troubled 1990s, has had discussions with Max Hospitals in Delhi, and Manipal medical institutions in Karnataka. He’s also pursuing leads in China and Italy.

After regulatory approval, it should take no more than cryo and cell-culture facilities—to keep viruses and stem cells alive and replicate masses of them—to get started, said Shah, explaining that different types of brain tumours would require specially tailored stem cells for each molecular variation of the cancer.

What might one such facility cost? “`1 crore and then (hosting) me,” he said, smiling. Eventually, Shah—in his spare time a cricket enthusiast who bowls leg-spin—hopes to stick a needle into a tumour, determine its strain and start specific treatment. Therapies will be tailored, “like a pill”, he said.

Shah’s brain-tumour killer, the herpes virus, is a common viral infection worldwide, spreading through skin contact, its two versions attacking either the face or genital areas. There is no cure and once you have it, the virus stays in the body, sometimes making its presence felt but usually dormant in nerve cells.

The virus that Shah and his colleagues use is attenuated, or weakened, genetically engineered to reproduce only in replicating cells. That allows the herpes virus to attack only multiplying tumour cells. Like the influenza virus, if it doesn’t see a replicating cell, it dies—and so does the stem cell.

The idea of using oncolytic viruses against brain tumours is not new, but it hasn’t been particularly successful. The main problem was that the herpes virus was washed out by cerebrospinal fluid, a colourless liquid that bathes the spinal cord and brain, acting as a shock absorber for the brain within the skull and ferrying nutrients and waste products.

Shah and his team fixed that problem by using a gel, into which they mixed herpes-virus-loaded human mesenchymal stem cells—for this approach, they now have a patent.

Mesenchymal stem cells usually form into bone-marrow tissue and trigger only a muted response from the immune system. After application on brain tumours grown in mice, the gel kept the stem cells from getting washed away, before degrading harmlessly. In the case of cancer cells resistant to the herpes virus, Shah and his team engineered it to express a gene that allows the virus to kill a broad spectrum of tumours. When the cancerous cells stop multiplying, there is nothing for the herpes virus to infect, and it dies.

“There is no rocket science here,” said Shah. “Herpes is as old as human beings, tumours too. Bone-marrow stem cells have also been around for some time. This is basic biology, all organic, Whole-Foods (a popular grocery chain) stuff; we have just played around with the ingredients. It’s an old story with a new twist.”

Tense exit, triumphant return

Shah remembers his stressful exit from New Delhi. On 14 August 1995, the eve of his departure and of Independence Day, he was at a friend’s apartment in Lajpat Nagar, a bustling, noisy middle-class neighbourhood where Kashmiris often stay. “’Where are you from?’ they asked me,’” recalled Shah, a youthful looking man with a neatly trimmed moustache. “I was so scared. When I said Kashmir, of course, they questioned me for a long time.” The officers let him off eventually when he explained his academic plans and showed them his ticket to Europe.

But the scars of growing up in embattled Kashmir did not immediately go away. In Germany, where Shah did his masters and Phd in genetic engineering, he was once startled during a celebration when firecrackers exploded. “I was shivering,” he said. Shah dived for cover, conditioned by the violent streets of his hometown, Srinagar, then in the throes of an armed insurrection against Indian rule.

Today, Shah talks of transferring to India his talent and medical advances. He travels there often, giving talks and exploring collaborations. In Boston, he is an enthusiastic mentor, talking science with high-school students, often taking his laboratory staff with him. In recognition, Harvard Medical School recently honoured him with a young mentor award.

The other thing he has not forgotten is the subcontinental way of dealing with people. When I arrived at a Boston subway station and prepared to transfer to a shuttle to Shah’s research facility, I found he had come to pick me up in his car. “I have lived so long outside India,” he said. “I don’t want to lose the personal touch, I don’t want to forget where I came from.”

Samar Halarnkar is a Bangalore-based journalist. This is a fortnightly column that explores the cutting edge of science and technology.

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