Researchers claim to have identified two compounds that could remyelinate damaged nerve fibers in people with multiple sclerosis. Successful remyelination through a compound could restore faster nerve conduction and may help reduce long-term disability linked to the disease.

MS is a chronic autoimmune disease affecting more than 2.9 million people worldwide. It occurs when the immune system mistakenly attacks the myelin sheath, the protective insulation around axons, nerve fibers, causing disruption of signals between the brain and body. Symptoms can include numbness, tingling, vision loss, and paralysis.

While current treatments can reduce inflammation, no therapies exist to protect neurons or restore the damaged myelin sheath. Researchers have now taken a major step forward in the development of such a therapy. 

The research, led by scientists at the University of California, Riverside, School of Medicine builds on earlier work involving a compound called indazole chloride, known for promoting remyelination and modulating the immune system in mouse models of MS. While effective, indazole chloride lacked the pharmacological properties and patentability needed for clinical development and commercial investment, according to the researchers.

In collaboration with University of Illinois Urbana-Champaign chemists, the researchers screened more than 60 indazole chloride analogs. This collaboration identified two candidates – K102 and K110 – that exhibited improved safety, efficacy, and drug-like properties in both mouse models and human cells.

Of the two, K102 emerged as the lead compound. The researchers found it not only promotes remyelination but also modulates immune function, an important balance for MS therapies. It also showed promising results in human oligodendrocytes, the myelinating cells of the central nervous system, derived from induced pluripotent stem cells, suggesting the potential for translatability between the animal models and human disease.

Under normal conditions, oligodendrocyte precursor cells mature into myelin-producing oligodendrocytes to repair damaged myelin. In MS, however, this natural repair process often fails, leading to permanent nerve damage. Successful remyelination through a compound such as K102 could restore faster nerve conduction and may help reduce long-term disability linked to the disease.

Though the initial focus is MS, the research team believes K102 and K110 could eventually be applied to other diseases involving neuronal damage, including stroke and neurodegeneration. The researchers are now advancing K102 through the necessary nonclinical studies required to support first-in-human clinical trials.

The findings were published in the journal Scientific Reports.