A 300-patient UK trial is testing whether an HIV drug, Triumeq, can slow or halt the paralysis of amyotrophic lateral sclerosis (ALS), also known as motor neuron disease. ALS kills most patients within three years of diagnosis, and the only approved treatment, Riluzole, extends survival by about 38% at one year. The trial builds on evidence that a dormant virus embedded in the human genome—a human endogenous retrovirus called HERV-K—may become reactivated in ALS and trigger motor neuron death. Triumeq, a combination antiretroviral that crosses the blood-brain barrier, suppressed HERV-K in a smaller Australian safety study and showed promising signals of efficacy. If Triumeq proves effective in this phase 2b trial, it would become the second disease-modifying therapy for ALS. The drug is already licensed and has a known safety profile, so a positive result could move rapidly into clinical use. The trial also tests whether blood and urine biomarkers can track disease progression, which could speed future drug development. Patients are monitored every three months to reduce clinic visits. Results will be published in scientific journals and shared through the MND Association.
View original technical description
Research Question: Is the antiretroviral therapy Triumeq an effective treatment for amyotrophic lateral sclerosis (ALS)? Background: Amyotrophic lateral sclerosis(ALS), also known as Motor Neuron Disease (MND), is an adult-onset neurodegenerative disease of the corticospinal motor system, resulting in progressive paralysis of voluntary muscles until death occurs, usually from respiratory failure, typically within 3 years of onset. It has a mean age of onset of 56 years, and the risk increases with age. The incidence is 1-2 per 100,000 person-years, prevalence about 5 per 100,000, and lifetime risk 1 in 300, with a male:female ratio of 3:2. There is no cure, and the only disease-modifying therapy, Riluzole, improves 1 year survival by about 38%. It is a greatly feared diagnosis, and the most frequent cause of assisted suicide. There is therefore a significant unmet need for an effective disease modifying therapy. In 5% of people there is a family history of ALS, and for about 80% of such cases, and for about 18% of those without a family history, a genetic cause has been identified. Regardless of genetic background, we and others have shown that a human endogenous retrovirus (HERV), may contribute to disease onset, becoming activated, and leading to the death of motor neurons. This type of virus is in the same class of viruses as HIV, which also shows the same ability to integrate itself into the genome. A specific HERV, known as HERV-K, has been implicated in ALS. A combination antiretroviral drug with a good safety record, Triumeq, is effective against HIV and is able to cross the blood brain barrier. Triumeq also shows efficacy against HERV-K. In the Lighthouse I Study, a phase 2a safety and tolerability trial of Triumeq in ALS carried out in Australia, it met its primary outcomes. Even though the study was not designed to assess efficacy, the results were promising in all parameters of outcome, including suppression of HERV-K, and need urgent follow up in a larger Phase 2b trial. Aims and Objectives: To carry out a Phase 2b clinical trial of the antiretroviral drug, Triumeq, in people with ALS. Methods: We therefore plan to test Triumeq in ALS in a randomized, double-blind, placebo-controlled trial in multiple specialist and non-specialist centres in the UK, recruiting 300 patients, half to be given placebo and half active therapy, with at least 2 years follow up. The study will test whether there is an improvement in the survival rate and function of people on Triumeq, and will explore whether biomarkers (blood and urine measurements of disease status) are effective for monitoring disease progression. We will also measure the quality of life of people with ALS taking part in the study. If there is a positive effect, we will apply to extend licensing in ALS. Patients will be monitored every three months to minimise the need for face-to-face attendance at clinics. Timelines for Delivery: Patients will be followed up for a minimum of two years. Patients will follow standard care, with outpatient clinics every 3 months. Anticipated Impact and Dissemination: A treatment benefit will be a significant advance in our knowledge and treatment of ALS. Results will be made available through scientific journals, the MND Association website, press release, and social media.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know