The disease starts with a feeling of increased clumsiness. Spilling a cup of coffee. Stumbling on the stairs. Having accidents that are easy to dismisseveryone trips now and then.

But it inevitably gets worse. Known as familial amyloid polyneuropathy, or FAP, it can go misdiagnosed for years as patients lose the ability to walk or perform delicate tasks with their hands. Most patients die within 10 to 15 years of the first symptoms.

There is no cure. The disease is caused by malformed proteins produced in the liver, so one treatment is a liver transplant. But few patients can get oneand it only slows the disease down.

Now, after years of false starts and disappointment, it looks like an audacious idea for helping these patients finally could work.

In 1998, researchers at the Carnegie Institution and the University of Massachusetts made a surprising discovery about how cells regulate which proteins they produce. They found that certain kinds of RNAwhich is what DNA makes to create proteinscan turn off specific genes. The finding, called RNA interference (RNAi), was exciting because it suggested a way to shut down the production of any protein in the body, including those connected with diseases that couldnt be touched with ordinary drugs. It was so promising that its discoverers won the Nobel Prize just eight years later.

The world went from believing RNAi would change everything to thinking it wouldnt work, to now thinking it will.

Inspired by the discovery, another group of researchersincluding the former thesis supervisor of one of the Nobel laureatesfounded Alnylam in Cambridge, Massachusetts, in 2002. Their goal: fight diseases like FAP by using RNAi to eliminate bad proteins (see The Prize of RNAi and Prescription RNA). Never mind that no one knew how to make a drug that could trigger RNAi. In fact, that challenge would bedevil the researchers for the better part of a decade. Along the way, the company lost the support of major drug companies that had signed on in a first wave of enthusiasm. At one point the idea of RNAi therapy was on the verge of being discredited.

But now Alnylam is testing a drug to treat FAP in advanced human trials. Its the last hurdle before the company will seek regulatory approval to put the drug on the market. Although its too early to tell how well the drug will alleviate symptoms, its doing what the researchers hoped it would: it can decrease the production of the protein that causes FAP by more than 80 percent.

This could be just the beginning for RNAi. Alnylam has more than 11 drugs, including ones for hemophilia, hepatitis B, and even high cholesterol, in its development pipeline, and has three in human trials progress that led the pharmaceutical company Sanofi to make a $700 million investment in the company last winter. Last month, the pharmaceutical giant Roche, an early Alnylam supporter that had given up on RNAi, reversed its opinion of the technology as well, announcing a $450 million deal to acquire the RNAi startup Santaris. All told, there are about 15 RNAi-based drugs in clinical trials from several research groups and companies.

The world went from believing RNAi would change everything to thinking it wouldnt work, to now thinking it will, says Robert Langer, a professor at MIT, and one of Alnylams advisors.

Read more from the original source:
Gene-Silencing Drugs Finally Show Promise

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