I often marvel at the disconnect between media coverage of "breakthrough" treatments and the decades of research that lie behind them. A new drug is the culmination of basic research, preclinical experiments on animals and cells, three phases of clinical trials, and post-marketing surveillance. It takes decades.
A small, phase 1 study – safety in healthy people – caught my attention this week. The work was presented at the American College of Cardiology's annual meeting and published online in the Journal of the American Medical Association.
The healthy participants had elevated levels of apolipoprotein(a), which is made in the liver and goes to the blood, where it carries cholesterol. High levels raise risk of heart attack, stroke, and narrowing of the aorta. Could silencing the gene that encodes the protein portion of apolipoprotein(a) lower the level, perhaps even preventing the heart disease?
One way to silence a gene uses a natural process, RNA interference (RNAi), which blocks translation of a gene's information into construction of a specific protein. The first drug using RNAi was Onpattro, approved in 2018 to treat a rare form of amyloidosis. The disease causes tingling, tickling, and burning sensations and affects about 3,000 people in the US.
In the new study, the researchers injected tiny pieces of short interfering RNAs (siRNAs), which glommed onto the messenger RNAs for the protein part of apolipoprotein(a). The 32 healthy volunteers received placebo or ascending doses. Levels of apolipoprotein(a) fell in a dose-dependent manner, by about 98 percent for the highest-dose group. All doses were well tolerated and the lowering largely persisted when checked at five months.
To continue reading, go to my blog, DNA Science, at Public Library of Science.