#BlackSwan: anecdotal evidence we can’t ignore

Barts-MS rose-tinted-odometer: ★★★★★

What is a black swan event? 

“The black swan theory or theory of black swan events is a metaphor that describes an event that comes as a surprise, has a major effect, and is often inappropriately rationalised after the fact with the benefit of hindsight”. (Source Wikipedia)

The case study below is another example of a mounting number of case studies of patients with MS being treated with antivirals, with activity against EBV, doing well. We now need to do properly powered randomised controlled trials to test the EBV causation of MS hypothesis definitively. 

Prof. Julian Gold and I launched the Charcot Project in 2012 to investigate the viral aeitology of MS. We tried on numerous occasions to get trials funded to test this hypothesis and have failed. We managed to test one anti-retroviral in a small proof-of-concept study, which was negative. Since then we have managed to get funding to see if famciclovir is capable of suppressing EBV shedding in the saliva. This study should have been completed by now, but we had to delay its start because of the COVID-19 pandemic. 

We have also managed to show that teriflunomide is anti-EBV in that it reduces EBV viral shedding in the saliva of people with MS. I suspect this is a very relevant an important observation and underpins the iTeri study, i.e. to use a B-cell depleting agent as induction therapy and teriflunomide or related compound as a maintenance therapy to prevent EBV reinfecting B-cells during the B-cell reconstitution phase. 

Life is short and I started working on EBV as a cause of MS way back in 2005 and feel like I am treading water. The evidence that EBV is the cause of MS is so overwhelming that we really can’t afford to ignore it any longer. What we need is a substantial investment from the major funding agencies, MS charities, wealthy philanthropists and Pharmaceutical companies with antiviral drugs in their portfolio to prove (or disprove) that EBV is the cause of MS. 

When you apply Bradford-Hill’s causation theory to EBV being the cause of MS  there is only one criterion out of nine that still needs to be ticked and that is experimental evidence. What we need are therapeutic interventional trials targeting EBV to complete the proof. 

Torkildsen et al. Tenofovir as a treatment option for multiple sclerosis. Mult Scler Relat Disord 2020 Oct 7;46:102569. doi: 10.1016/j.msard.2020.102569.

Some antiretroviral medications are also inhibitors of EBV. We describe a patient with highly active MS who was infected with HIV and started HIV-treatment containing tenofovir alafenamide (TAF), a potent inhibitor of EBV lytic reactivation. Her MS was in complete remission during this treatment, and she had new radiological disease activity again after switching to tenofovir disoproxil fumarate, an HIV drug with less potent activity against EBV replication. Based on the recently detected mechanism of TDF and TAF, we suggest that further studies on these drugs in MS are warranted.

CoI: multiple

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