In silico screening and preclinical validation identify bavisant as a therapeutic candidate for multiple sclerosis

Area of Science:

• Neuroscience
• Pharmacology
• Regenerative Medicine

Background:

• Current multiple sclerosis (MS) treatments fail to halt neurodegeneration and disability progression.
• Therapeutics promoting myelin regeneration and neuroprotection are critically needed for progressive MS.
• Developing novel treatments for MS remains a significant unmet medical need.

Purpose of the Study:

• To identify and validate novel therapeutic compounds for progressive multiple sclerosis (MS).
• To investigate the potential of repurposed drugs for promoting remyelination and neuroprotection in MS.
• To evaluate bavisant, a histamine receptor H3 antagonist, as a candidate for MS treatment.

Main Methods:

• In silico screening of over 1500 repurposed compounds for predicted effects on myelination and neuroprotection.
• In vitro validation using rodent and human oligodendroglia and neurons.
• In vivo validation in mouse models of demyelination and axonal injury, including EAE and chimeric models.

Main Results:

• Identified 32 molecules with promyelinating and neuroprotective effects on oligodendroglia and neurons.
• Bavisant demonstrated significant remyelination and neuroprotection in multiple preclinical models of MS.
• Distinct compound classes with potential mechanisms for fostering remyelination and neuroprotection were identified.

Conclusions:

• Bavisant shows proof-of-concept as a promising candidate for neuroprotective clinical trials in multiple sclerosis (MS).
• The study validates a strategy combining in silico screening and in vitro/in vivo validation for drug discovery in MS.
• Further research into bavisant and other identified compounds could lead to effective treatments for progressive MS.