Author: Joaquín Castilla
A clinical trial registered on ClinicalTrials.gov is evaluating whether efavirenz, a drug used for years in the treatment of HIV, can provide benefit in Creutzfeldt-Jakob disease (CJD).
According to the registry, which compiles all experimental drug trials in humans, this is a multicenter, randomized, double-blind, placebo-controlled study. This means the study will be conducted in different hospitals, where patients will be randomly treated with either a placebo or the drug, without the doctors or study participants knowing who is receiving the placebo and who is receiving the drug. The study is being led by Xuanwu Hospital in Beijing, and the latest available update shows that recruitment is still open, meaning that the treatment has not yet begun for any patients.
Important: This trial is exclusively for people residing in China.
The primary objective of the study is very clear: to determine whether efavirenz can prolong survival in people with CJD. Participants will receive either efavirenz or a placebo, and the treatment will be administered orally, starting with 200 mg daily for the first week and then increasing to 400 mg daily. Inclusion criteria include patients aged 18 to 80 years with probable sporadic CJD or a genetically confirmed hereditary form, who still maintain some functional capacity and have a caregiver who can accompany them during the study.
Why was this drug tested on prions ? The reason lies in a recent preclinical study published in JCI Insight , in which efavirenz was studied in mice genetically modified to express the human prion protein and infected with sporadic CJD prions. In that model, oral treatment slowed disease progression and prolonged survival, even when started relatively late in the experimental process.
In addition to its effect on survival, researchers observed less accumulation of the abnormal prion protein and improved cholesterol regulation in the brain during the early stages of the disease. Specifically, they saw changes consistent with the activation of an enzyme called CYP46A1, which helps maintain cholesterol balance in the brain. Simply put, the drug not only appeared to slow part of the pathological process but also to correct metabolic alterations in the brain that could contribute to the deterioration caused by the disease.
In the experimental model, the average survival gain was 17 days when treatment started earlier and 23 days when it started later. Although these results cannot be directly extrapolated to humans, they are robust enough to justify testing efavirenz in patients now.
However, caution is advised. To date, there are no published clinical results in people with CJD for this trial. What does exist is a promising experimental basis and a study designed to verify whether this benefit is confirmed in real patients, assessing survival, functional evolution, and treatment safety.
For families and the prion disease community, this news doesn’t mean an effective treatment is now available, but it does represent something important: a known drug, with prior experience in other diseases, has generated sufficiently encouraging data to move into clinical trials for CJD. And in a field with so few therapeutic options, that is already significant news, so the Foundation will follow the study’s progress with great interest.