IISc scientists make progress on new thyroid drug

IISc scientists make progress on new thyroid drug

New Delhi: A team of scientists at the Bangalore-based Indian Institute of Science (IISc) has synthesized a key molecule that could potentially translate into a drug for hyperthyroidism, a disorder that’s increasingly associated with a host of lifestyle diseases.

If successful, the chemical entity could contain thyroid levels without side effects such as excessive balding and jaundice, commonly associated with the relevant drugs, the researchers added. It would be the first successful molecule for hyperthyroidism to come out of an Indian lab.

“We are still very much in the pre-clinical stage," said Govindasamy Mugesh, associate professor, department of inorganic and physical chemistry, IISc. “We’ve synthesized the molecule and have seen that the underlying mechanism works. But animal studies and clinical trials are a long way off."

The findings of the team were published on Wednesday in the peer-reviewed Angewandte Chemie (international edition), a top chemistry journal published out of Germany.

The basic “mechanism" that Mugesh refers to involves circumventing the approach that the contemporary drugs use. Hyperthyroidism involves the over-production of key thyroid hormones called T3 and T4.

The current drug approach to stemming the disease involves cutting the levels of iodine—the key thyroid regulator—by mimicking an enzyme called deiodinase, which completely blocks their production. “That works negatively because these hormones are responsible for practically every metabolic function in the body. So, complete shutdown could trigger side effects and even hypothyroidism, which comes with its own problems," said Mugesh.

His team has developed a completely new compound that only lowers—and doesn’t entirely deplete—T3 and T4 levels. “Therefore, the optimum balance is maintained," he said.

Previous efforts to mimic deiodinase to develop a drug for practical use have been unsuccessful, said V.S. Dubey, a Delhi-based endocrinologist and a former adviser to the government on women’s health.

Typically, hyperthyroidism affects women more than men, and according to estimates by the health ministry, there are at least 10 million patients afflicted with the disorder to varying degrees in India.

Dubey said that an erratic diet, increasing stress levels at work and a rising urban trend of women opting for delayed pregnancies were correlated to hyperthyroidism disorders.

“It’s not a killer disease, but changing lifestyles such as work-related stress, late births all impact women far more adversely. In fact, one of the key signs of polycystic ovarian syndrome (which affects one in 10 Indian women) are thyroid-related disorders," he said.

Others say Mugesh’s results are interesting but there’s a high risk of failure with the chemical eventually revealing some side effects during clinical trials.

“It’s a useful finding, but I would wait at least for preliminary level clinical trials before I got really excited," said C.R. Pillai, an emeritus scientist with the Indian Council for Medical Research. “Wet labs (synthesizing compounds in the lab) are usually very successful, but clinical trials can break even the most promising of candidate drugs."