UK study questions safety of new class of drugs

A new class of drugs that are supposed to turn off unwanted genes may not work as originally thought, according to a new study by a University of Kentucky researcher that was published Wednesday in Nature.

The drugs, based on Nobel Prize-winning research, are designed to stop the progression of diseases like macular degeneration, an age-related eye disease, by shutting off the gene that causes the disease. The process is called gene silencing.

But, according to a study by Dr. Jayakrishna Ambati, the drugs don’t work as intended. In the case of macular degeneration, the drugs don’t just inhibit blood vessel growth in the eye — they inhibit blood vessel growth in other parts of the body.

“You don’t just want to stop blood vessel growth everywhere,” said Ambati, a professor of ophthalmology at UK.

The drugs are supposed to mimic a process called RNA interference, which occurs naturally in cells, and allows the body to prevent the expression of specific genes.

When RNA interference occurs naturally, the process happens inside the cell. But the synthetic molecules, called small interfering RNAs or siRNAs, don’t work the same way, Ambati said.

They can’t get inside the cell because they are too large and have the wrong electrical charge. Instead, they bind to a receptor on the outside of the cell.

This receptor doesn’t distinguish between molecules designed to block blood vessel growth in the retina or ones designed to block blood vessel growth elsewhere, he said

“It generically blocks blood vessel growth, regardless of what your sequence is,” Ambati said.

In tests done by Ambati’s lab on mice, the molecules blocked vessel growth in the eye, skin and other organs.

Humans have the same receptor on their cells, Ambati said.

“It’s entirely possible and, actually quite likely, that this type of interaction occurs in humans as well,” Ambati said.

The study results show why scientists should be careful when testing new technologies on people, Ambati said.

“We should take a fresh, new look into how these drugs work and not proceed headlong in injecting these drugs into people and not know how these things work,” he said.

For more on this study, see Thursday’s Herald-Leader.

Reach Sarah Vos at (859)231-3309 or 1-800-950-6397, Ext. 3309.