A team in Germany is planning to launch a trial with the drug IMU-838 trial for Long Covid. Currently there aren’t too many details on the trial, however Maria Vehreschild of the Universitätsklinikum Frankfurt has given some details in this talk www.vimeo.com/873993707/description (from 32:30 onwards). The plan is to do a RCT with 45mg of IMU-838 daily for 56 days, which is a higher dosage, albeit for a much shorter time, then is being used in the currently running Phase 3 trial for MS https://www.clinicaltrials.gov/study/NCT05134441. She presents the ideas for the trial as follows: blocks intracellular viral replication -> reduction of viral loads of SARS-COV-2, EBV, CMV, etc (dosage dependent inhibition of EBV reactivation in B-cells & to some degree reduces lytic infection in epithelial cells) reduces Lymphocyte activation -> less cytokines -> anti-inflammatory It seems that they are hoping to aim at very similar mechanisms which this drug could possibly be addressing in MS (anti-inflammatory properties and possibly EBV reactivation). Very recently some positive trial results of the Phase 2 study in MS have been announced https://imux.com/immunic-reports-po...us-calcium-in-progressive-multiple-sclerosis/. The IMU-838 trials are the “top ranked” trials on this MS trial database (which however is run by patients focusing on the EBV-MS hypothesis) www.docs.google.com/spreadsheets/d/1_snDrKohhyyyF_RnR3oZRevFcMGJIBXlaMytpG9Ecus/edit#gid=1393287940. The big caveat is that this drug is just a small update to already existing DHODH inhibitors (which could of course mean quite a bit for a person with MS) and I have never heard anybody suggest exploring these older DHODH inhibitors in Long Covid or ME/CFS, especially not with Rituximab failing. There is also some data on the direct antiviral effects for SARS-COV-2 in vivo with the EC50 not being particularly great https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762174/ with leflunomide and teriflunomide having similar EC50s https://pubmed.ncbi.nlm.nih.gov/36437966/, https://pubmed.ncbi.nlm.nih.gov/34111397/. I’m sure @Jonathan Edwards will have some comments on this.
For those who don't know about DHODH inhibitors "About Vidofludimus Calcium (IMU-838) Vidofludimus calcium is a small molecule investigational drug in development as an oral next-generation treatment option for patients with multiple sclerosis and other chronic inflammatory and autoimmune diseases. The selective immune modulator activates the neuroprotective transcription factor nuclear receptor related 1 (Nurr1), which is associated with direct neuroprotective properties. Additionally, vidofludimus calcium is a known inhibitor of the enzyme dihydroorotate dehydrogenase (DHODH), which is a key enzyme in the metabolism of overactive immune cells and virus-infected cells. This mechanism is associated with the anti-inflammatory and anti-viral effects of vidofludimus calcium. Vidofludimus calcium has been observed to selectively act on hyperactive T and B cells while leaving other immune cells largely unaffected and enabling normal immune system function, e.g., in fighting infections. To date, vidofludimus calcium has been tested in more than 1,400 individuals and has shown an attractive pharmacokinetic, safety and tolerability profile. Vidofludimus calcium is not yet licensed or approved in any country." Above para is from https://imux.com/immunic-reports-po...us-calcium-in-progressive-multiple-sclerosis/
