Masitinib lowers nerve damage, slows disease progression in mice
Therapy is being developed by AB Science for progressive forms of MS
Treatment with masitinib, an experimental therapy being developed by AB Science for progressive forms of multiple sclerosis (MS), reduced markers of nerve damage and inflammation and slowed disease progression in a mouse model of MS.
“This study is the first to demonstrate that masitinib can lower serum NfL levels, a key biomarker of neuronal damage, while also reducing neuroinflammation and slowing functional decline in a neuroimmune-driven disease model,” Olivier Hermine, MD, president of AB Science‘s scientific committee and co-author of the study, said in a company press release. The study, “Tyrosine kinase inhibitor, masitinib, limits neuronal damage, as measured by serum neurofilament light chain concentration in a model of neuroimmune-driven neurodegenerative disease,” was published in PLOS One.
In MS, inflammation damages healthy parts of the brain and spinal cord. Masitinib is an oral molecule that’s designed to block the activity of certain proteins called tyrosine kinases, namely those involved in activating certain types of inflammatory immune cells in MS. The therapy seeks to slow MS disease progression by reducing the activity of those cells.
Reinforcing masitinib’s ‘therapeutic promise’
Data from a completed Phase 2b/3 trial, called AB07002 (NCT01433497), indicated masitinib significantly slowed disability progression relative to a placebo in people with primary progressive (PPMS) and nonactive secondary progressive MS (SPMS).
That study supported the launch of an ongoing Phase 3 clinical trial called MAXIMS (NCT05441488) whose participants are receiving the medication or a placebo, given orally twice daily for about two years.
“Masitinib has already shown clinical benefits in progressive MS … in previous trials, and this study further strengthens its therapeutic promise,” Hermine said.
In the animal study, masitinib was tested in mice with experimental autoimmune encephalitis (EAE), a lab-induced disorder that’s commonly used to model MS.
The animals saw worsening mobility, muscle strength, and overall clinical scores over time. But those given masitinib had slower deterioration in grip strength, suggesting the oral therapy could slow some aspects of EAE disease progression.
Masitinib also led to lower blood levels of neurofilament light chain (NfL), an established marker of nerve fiber damage. Compared with untreated EAE mice, NfL levels were reduced by 43% with a low dose (50 mg/kg) and by 60% with 100 mg/kg after eight days of treatment.
At the same time, the therapy significantly lowered levels of pro-inflammatory signaling molecules, which is “consistent with a reduction in neuroinflammatory activity,” the researchers wrote. “This study is the first demonstration that masitinib can lower serum NfL levels in a neuroimmune-driven neurodegenerative disease model, with concomitant reduction in pro-inflammatory cytokines and slowing of clinical (EAE) symptoms.”
“These findings support masitinib’s potential as a disease-modifying therapy for neurodegenerative diseases,” Hermine said.
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