siRNA therapy shows promise for reducing genetic heart disease risk
In phase 1 trials, an experimental siRNA therapy has shown promise for reducing levels of a lipoprotein associated with a higher risk of premature heart disease. The treatment could help fight a form of the disease that can’t currently be treated through lifestyle changes.
Lipoprotein(a), or Lp(a), is a cholesterol-transporting protein made in the liver, and when circulating at elevated levels it contributes to the accumulation of plaque in arteries, greatly increasing the risk of cardiovascular disease, heart attacks and strokes. Unfortunately, Lp(a) levels are mostly determined genetically, so improving diet and exercise won’t reduce that risk.
In the new study, scientists have reported the first treatment that can reduce Lp(a) levels almost entirely. The APOLLO trial involved giving participants an injection of SLN360, a small interfering RNA (siRNA) molecule, which silences the gene behind Lp(a) production. All participants had Lp(a) levels at least twice that considered normal.
Of the 32 participants, eight received a placebo, while the others received SLN360 doses of either 30 mg, 100 mg, 300 mg or 600 mg. Patients were observed closely for 24 hours after injection, then examined periodically over the next five months.
Those that received a placebo saw little change in their Lp(a) levels over that time, but participants that received the drug saw drastic drops. Soon after the injection, Lp(a) levels dropped by 86 percent for patients that received 100 mg, 96 percent for those on 300 mg and 98 percent for the 600-mg group. Even after five months, the two highest doses still had Lp(a) levels 71 and 81 percent lower than baseline.
The highest doses also seemed to reduce levels of “bad” LDL cholesterol by up to 25 percent, and the team says that no adverse side effects were recorded. With follow-ups and further trials, it’s hoped that SLN360 or similar RNA treatments could help reduce the risk of cardiovascular diseases in predisposed patients.
"These results showed the safety and strong efficacy of this experimental treatment at reducing levels of Lp(a), a common, but previously untreatable, genetically-determined risk factor that leads to premature heart attack, stroke and aortic stenosis," said Steven E. Nissen, M.D., Chief Academic Officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic, and lead author of the study. "We hope that further development of this therapy also will be shown to reduce the consequences of Lp(a) in the clinical setting through future studies."
The research was published in the Journal of the American Medical Association. The team describes the work in the video below.
Source: Cleveland Clinic