Apolipoprotein(a) (apo(a)) is covalently bonded to apoB100 within a modified low-density lipoprotein (LDL) particle to form lipoprotein(a) (Lp(a)). A substantial amount of data points to Lp(a) as a causative factor in the processes that encourage calcific aortic valve disease and atherogenesis. Based on Mendelian randomization studies, a significant decrease in Lp(a) could be necessary in order to provide a significant therapeutic effect.

Olpasiran is a small interfering RNA (siRNA) molecule linked to N-acetylgalactosamine (GalNAc) that obstructs the expression of the LPA gene by causing the messenger RNA encoding apo(a) to break down, thereby stopping the hepatocyte from assembling the Lp(a) particle. Olpasiran is a small interfering RNA (siRNA) that inhibits the translation of apolipoprotein(a) mRNA, hence blocking the formation of lipoprotein(a) (Lp(a)). This research by Michelle O'Donoghue and colleagues evaluated both the longer-term safety and the timing of Lp(a) returning to baseline following olpasiran withdrawal.

In the phase 2 dose-finding trial OCEAN(a)-DOSE (Olpasiran Trials of Cardiovascular Events And LipoproteiN[a] Reduction–DOSE Finding Study), a total of 281 participants with atherosclerotic cardiovascular disease and Lp(a) >150 nmol/L were enrolled to receive one of four active doses of olpasiran versus placebo (10 mg, 75 mg, 225 mg Q12W, or an exploratory dose of 225 mg Q24W administered subcutaneously). Week 36 was the last dosage of olpasiran, and after week 48, there was a minimum 24-week prolonged off-treatment follow-up period.

276 individuals (98.2%) of the total study population started the post-treatment follow-up phase. The mean duration of the trial encompassed both treatment and non-treatment periods, was 86 weeks (Q1-Q3: 79-99 weeks). At 60, 72, 84, and 96 weeks, the off-treatment placebo-adjusted mean percent decrease from baseline in Lp(a) for the 75 mg Q12W dosage were −76.2%, −53.0%, −44.0%, and −27.9%, respectively (all P < 0.001).

For the 225 mg Q12W dosage, the corresponding off-treatment decreases in Lp(a) were −84.4%, −61.6%, −52.2%, and −36.4% (all P < 0.001). In the follow-up phase of the extension, no additional safety issues were found. Overall, the RNA interference of Olpasiran causes a significant decrease in Lp(a), with long-term pharmacodynamic effects that last for many months after therapy is stopped.

Source:

O’Donoghue, M. L., Rosenson, R. S., López, J. A. G., Lepor, N. E., Baum, S. J., Stout, E., Gaudet, D., Knusel, B., Kuder, J. F., Murphy, S. A., Wang, H., Wu, Y., Shah, T., Wang, J., Wilmanski, T., Sohn, W., Kassahun, H., & Sabatine, M. S. (2024). The Off-Treatment Effects of Olpasiran on Lipoprotein(a) Lowering. In Journal of the American College of Cardiology (Vol. 84, Issue 9, pp. 790–797). Elsevier BV. https://doi.org/10.1016/j.jacc.2024.05.058

View the full post Ministry of Health statement on infant deaths at The General Hospital on NOW Grenada.

The Centers for Disease Control and Prevention (CDC) on Tuesday reported 21 cases of Oropouche virus disease, also known as sloth fever, in travelers returning from Cuba.

Twenty cases have been reported in Florida and one in New York.

The disease is spread primarily through bites from midges and from some mosquitoes. Symptoms of the disease include headache, fever and muscle aches and joint pains, but the virus is rarely fatal. 

PARVOVIRUS OR ‘SLAPPED CHEEK DISEASE’ IS ON THE RISE, CDC WARNS: HERE’S WHAT TO KNOW

There is no indication that the virus is spreading in the U.S. but health officials are warning doctors to be on the lookout for infection in travelers coming from Cuba and South America.

Most patients returning from Cuba reported their symptoms between May and July.

Overall, three patients were hospitalized, and no deaths were reported, the CDC said in its Morbidity and Mortality Weekly Report.

A dire economic crisis in Cuba has made it difficult to control the spread of Oropouche. Frequent power outages mean many sleep with windows open during the hot Caribbean summer. Few Cubans have access to insect repellents, and fumigation efforts have been stymied by fuel shortages.

WITH MPOX A PUBLIC HEALTH EMERGENCY IN AFRICA, WHAT YOU MUST KNOW ABOUT INCREASED VIRUS RISK

Earlier this month, the CDC issued a Health Alert Network (HAN) Health Advisory about an increase in Oropouche virus disease in the Americas region. 

The virus is endemic to the Amazon basin and more than 8,000 cases have been reported in Brazil, Bolivia, Peru, Colombia, and Cuba so far this year, including two deaths, and five cases of vertical transmission, where viruses can pass between mother and fetus.

The CDC has recommended that pregnant women avoid non-essential travel to Cuba and suggested all travelers take steps to prevent bug bites, such as using insect repellents and wearing long-sleeved shirts and long pants. Currently, there are no vaccines available for the disease and treatment for symptoms can include rest, fluids and use of analgesics and antipyretics.

People can become infected when visiting these forested areas and getting bitten. They can then introduce the virus to urban areas, where biting midges and certain mosquitoes spread the virus from person to person.

Approximately 60% of people infected with Oropouche virus become symptomatic, according to the CDC. The incubation period is typically three to 10 days.

It has sometimes been called sloth fever because scientists first investigating the virus found it in a three-toed sloth, and believed sloths were important in its spread between insects and animals. 

The virus was first detected in 1955 in Trinidad and Tobago.

The Associated Press and Reuters contributed to this report.