The Lighthouse Project

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Update: July 2019

The initial results of the Lighthouse Project Phase 2 clinical trial have just been released.

What is the Lighthouse Project?
The Lighthouse Project is to test whether human endogenous retroviruses (HERVs) may play a role in motor neurone disease (MND) and whether targeting HERVs might provide a novel therapeutic avenue.

Approximately 8% of human genes originate from retroviruses which infected animals and humans over millions of years of evolution and their DNA was integrated into our genomes and becoming part of our genetic makeup.

HERVs were only discovered about 30 years ago and it is still not known exactly how or if they may cause disease. However, there is very good evidence in animals that these viruses are associated with a number of neurological conditions.

The Lighthouse Project is the first Phase 2 clinical trial in the world to use modern combination anti-retroviral therapy in patients with MND. Phase 2 trials usually extend the safety and tolerability studies undertake during the Phase I trial using more patients.

In addition, initial tests of the effectiveness of the treatment will also be investigated. This study aimed to determine the safety and tolerability of an anti-retroviral therapy, “Triumeq”, and provide preliminary data on whether it is able to slow down the progression of MND. Triumeq is already used to treat HIV infection safely and effectively.

The Lighthouse Project was supported by the Motor Neurone Disease Research Institute of Australia and the FightMND Foundation.

What was involved?
The Phase 2 study was conducted at Calvary Healthcare Bethlehem Hospital in Melbourne and three sites in Sydney; The Brain and Mind Centre at The University of Sydney, Macquarie University and Westmead Hospital.

The study recruited participants who had been diagnosed with sporadic amyotrophic lateral sclerosis (ALS) by a neurologist with neuromuscular sub-specialty training. Patients with known familial causes of MND were excluded.

Forty patients started Triumeq treatment and received Triumeq in tablet form (1 tablet/day – orally or crushed via a percutaneous endoscopic gastrostomy (PEG) tube) daily for 24 weeks after an initial 10 weeks of observation before starting treatment.

Assessment of safety and tolerability
Triumeq was well tolerated by MND patients with eighty-eight percent of the participants (n = 35) completing the 24-week treatment period. Four patients withdrew during the treatment period due to disease progression and one patient was withdrawn by the investigator due to a possible reaction to Triumeq.

Assessment of effects on disease 
To assess the potential benefits of Triumeq on disease progression a number of standard disease measurements were monitored.

All the disease measurements showed a similar trend with Triumeq treatment decreasing MND progression over the 6-month treatment period. It should be noted however that this was an open-label trial and thus there is a potential placebo effect for the clinical markers.

For the first time in a clinical trial setting, several biomarkers were also investigated to see whether they might be useful in providing simpler and more objective methods to measure disease progression and responses to treatment. The results from these biomarker studies are discussed in depth in the published report from the trial.

Summary
In summary, Triumeq appears to be safe and well tolerated in patients with MND.

It has considerable administration advantages as a single once-daily tablet which can be taken either whole or crushed. Moreover, it is already licensed for HIV treatment and is available in most countries.

Initial results indicate Triumeq may have a biological effect, both clinically and on biomarkers in patients with ALS and all effects appear to be positive.

However, this was only a small study and a much larger international multicentre phase 3 placebo-controlled trial is now planned to determine if Triumeq improves both survival and clinical progression. This definitive trial will be conducted in Europe, the U.K. and at five sites in Australia. It is hoped this trial will begin early in 2020.

For further information, Professor Julian Gold, the lead investigator on this study, can be contacted at Julian.gold@sydney.edu.au