A research team led by an Indian American scientist has challenged the validity of a prototype gene treatment based on Nobel prize winning work that has attracted billions of dollars in investment for developing cures for cancer, diabetes and other diseases.
The team, led by Jayakrishna Ambati, made the surprising discovery that the gene silencing method, rooted in a 1998 breakthrough that earned the Nobel prize for medicine in 2006, works not by targeting the specific culprit gene, but by having a generalised effect of blocking blood-vessel growth that could harm a wide range of tissues.
“That method was considered a breakthrough because then you could develop drugs to treat any disease as long as you knew what you were targeting,” said Ambati, an India-born professor of ophthalmology at the University of Kentucky.
Findings of the study have been published in the British science journal Nature. The study has put a question mark on the method that uses tiny synthetic molecules called small-interfering RNA (siRNA) to destroy specific disease bearing genes, thus blocking or reversing a disorder.
Pharmaceutical majors such as Merck and Pfizer have spent billions of dollars to develop drugs based on that method.
Now, the big implication of his team’s finding, Ambati said, is that the drugs these companies are developing will not work by the said mechanism but by generic blocking of blood vessels’ growth.
The good news, however, is that Ambati’s team is close to achieving a modified method of gene silencing that would not activate the blocking of blood vessel growth. “In a year or two we will be ready to come out with the modified method,” he said.
Once that happens, a group of drugs based on that method can be developed, said Ambati, adding that his university is applying for patents based on his work.
The Ambati team’s finding arose out of research on mice using siRNA strands designed to tackle age-related macular degeneration (AMD), a form of blindness that strikes late in life and affects 50 million people worldwide.
Ambati (37) was born in Vellore in Tamil Nadu. He came to the US with his family at the age of 10.
After completing medical school at the State University of New York and residency in ophthalmology at the University of Rochester, he did a fellowship at Harvard Medical School. He is currently vice chair of the Department of Ophthalmology and Visual Sciences at the University of Kentucky.