Post

1) A new randomized trial in Long Covid patients tested Temelimab, a drug that targets a potentially pathogenic protein (HERV-W ENV) from endogenous retroviruses. Unfortunately, the results are pretty clear: Temelimab had no beneficial effect.

2) Endogenous retroviruses are virus remnants that we inherit and are already inside our genome. Almost all of them are broken and switched off. The hypothesis, however, is that a viral infection such as SARS-CoV-2 may reactivate some of their functions.

3) After activation, some HERV-W sequences produce an envelope protein ("ENV") that the immune system reacts badly to. Temelimab binds to this protein to make sure it no longer acts as a false alarm for the immune system.

4) There were a couple of Long Covid studies that reported increased HERV-W ENV in Long Covid patients. This trial therefore used this as an inclusion criterion in their trial. It focused only on LC patients who were positive for HERV-W ENV in their blood.

5) This was a large placebo-controlled and international trial: it recruited 203 patients from three European countries (Switzerland, Italy, and Spain) involving 14 centers. The primary outcome was the PROMIS Fatigue SF 7a scale.

6) The main result is shown in the figure below. Temelimab had no effect on fatigue, and the same null results were seen for the secondary outcomes, including several cognitive tests and biomarkers.

7) The trial was sponsored by the Swiss biopharma company GeNeuro, which makes the drug. A couple of years ago, a randomized trial of Temelimab in multiple sclerosis also failed on its primary outcome. pubmed.ncbi.nlm.nih....

8 ) In the Long Covid trial, the authors conclude: "The absence of a treatment effect across fatigue, cognitive, and functional outcomes in our study may suggest that HERV-W ENV-associated pathways are not dominant drivers of symptoms [...]"

Oddly though, there wasn’t a large decrease in the amount of HERV-W protein in the blood after or during the treatment period The small decrease was the same in treatment & placebo groups Same with blood cytokine levels

Yeah I noticed this as well but wasn't entirely sure what it means, the paper doesn't go much further info on this.