Next-Generation MS Treatments: Beyond BTK Inhibitors

Multiple sclerosis (MS) researchers and pharmaceutical companies are pushing the boundaries of treatment options, looking beyond the much-anticipated Bruton's tyrosine kinase (BTK) inhibitors to explore neuroprotective and remyelination strategies. This shift in focus could potentially revolutionize MS treatment, moving from symptom management to disease modification and even reversal.

BTK Inhibitors: Promise and Challenges

BTK inhibitors have been hailed as a potential game-changer in MS treatment. These oral small molecule drugs block B cell signaling to reduce inflammation in both the central nervous and peripheral immune systems. Sanofi's tolebrutinib is leading the pack with an FDA target action date of December 28, while Roche's fenebrutinib has shown promising results in Phase II trials.

However, safety concerns have cast a shadow over this class of drugs. Both tolebrutinib and fenebrutinib have faced partial clinical holds due to cases of liver injury, creating uncertainty in the industry.

Neuroprotection: A New Frontier

Immunic Therapeutics is taking a different approach with vidofludimus calcium, which activates the Nurr1 protein. This mechanism is associated with maintaining neuron health and could offer both anti-inflammatory and neuroprotective effects.

"We had developed both an anti-inflammatory and a Nurr1 activator, which differentiates the drug from other treatments that work solely through an anti-inflammatory effect," said Andreas Muehler, co-founder and chief medical officer at Immunic Therapeutics.

Phase II results for vidofludimus calcium showed a 20% reduction in the relative risk of confirmed disability worsening events compared to placebo, with a 30% reduction in patients with primary progressive MS.

Remyelination: The Holy Grail

Researchers are also exploring treatments that could potentially reverse MS progression by encouraging remyelination. An international team, including Iain Greig from the University of Aberdeen, is developing a treatment targeting excitotoxicity to promote myelin rebuilding and nerve recovery.

"Clearly, this is a dream scenario, but our pre-clinical data support this as a real possibility," Greig stated. The research is currently in the final preclinical stages of validation.

Meanwhile, University of Cambridge researchers have presented Phase II clinical trial results indicating that a combination of metformin and clemastine shows potential for myelin repair.

Nick Cunniffe, a clinical lecturer in neurology at the University of Cambridge, expressed optimism: "My instinct is that we are on the brink of a new class of treatments to stop MS progression, and within the next decade we could see the first licensed treatment that repairs myelin and improves the lives of people living with MS."

As the MS treatment landscape evolves, these emerging approaches offer hope for more effective management and potential reversal of this challenging neurological condition.