These were the main findings from the series of preclinical studies:
Proof of concept data from the preclinical trials of masitinib showed that the investigational drug “targets neurotoxic aberrant glial cells by inhibiting CSF1R, providing a neuroprotective effect in the therapeutic setting and slowing down neurodegeneration,” according to a company press release.
Preliminary data also showed that “masitinib reduces inflammation in the CNS and in the peripheral nervous system (PNS),” and “penetrates the blood-brain-barrier more extensively than previously thought.”
Previous research demonstrates that likely alterations in the function of the blood-brain-barrier (BBB) in people with neurodegenerative diseases such as ALS exacerbate the difficulties in delivering effective disease modifying therapies that can treat the disease directly. Due to the documented challenges of crossing the BBB in treating such diseases, masitinib’s ability to cross the barrier in early testing, in addition to its neuroprotective qualities, could pave the way for continued development.
“Beyond what has been recently published in the scientific literature, we continue to develop our understanding of how masitinib generates the observed neuroprotective effect in ALS,” Prof. Olivier Hermine, president of AB Science’s Scientific Committee, said in the press release.
“For example, in addition to masitinib’s observed neuroprotective effect on the central nervous system we now have ALS model data demonstrating it can regulate neuroinflammation in the peripheral nervous system. Moreover, new preliminary data show that masitinib penetrates the blood-brain-barrier to a greater extent than previously thought, a finding that is also of importance for its development in other neurodegenerative indications, such as Alzheimer’s disease.
“Overall, these data provide a robust pharmacological rationale for the treatment of ALS with masitinib, while equally conveying plausibility to the recently reported positive Phase 3 interim analysis,” Hermine said.
AB Science develops protein kinase inhibitors (PKIs). Masitinib is a new orally administered tyrosine kinase inhibitor (TKI) that targets mast cells and macrophages, important for immunity, through the inhibition of a limited number of kinases.
With its singular mechanism of action, masitinib can be developed in a number of conditions in oncology, in inflammatory diseases, and in certain diseases of the central nervous system (CNS). In ALS, masitinib is particularly important due to its activity on mast cells and microglia, inhibiting the activation of the inflammatory process.
“Tyrosine kinase inhibition with masitinib appears unique among other ALS-developmental drugs because it exerts neuroprotection when administrated post-paralysis,” said Prof. Luis Barbeito, head of the neurodegeneration laboratory at Institut Pasteur in Montevideo, Uruguay.
“One advantage of using models in an advanced therapeutic setting is to closely simulate the clinical condition of ALS patients and their therapeutic needs, thereby increasing the likelihood of replicating the effect in humans. These data therefore provide compelling evidence for masitinib’s therapeutic potential in ALS,” he said.
Here are the four 2016 presentations (two of them have already taken place, but the others are still open for registration):
- 12th Andre-Delambre Annual Symposium on ALS (Andre-Delambre 2016), Sept. 16-17, Quebec City, Canada.
Title: “A rationale for post-paralysis tyrosine kinase inhibition [by masitinib] in ALS therapy.” Presenter: Prof. Luis Barbeito.
- 15th Annual NEALS Meeting (NEALS 2016), Oct. 5-7, Clearwater Beach, Florida.
Title: “Masitinib significantly slows down disease progression in postparalysis transgenic SOD1 G93A (ALS) rats and reduces inflammation in both central and peripheral nervous systems.” Presenter: Prof. Luis Barbeito.
- Second Congress of the Federation of Latin-American and Caribbean Societies for Neuroscience (FALAN 2016), Oct. 17-20, Buenos Aires, Argentina.
Title: “Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows down disease progression in inherited amyotrophic lateral sclerosis.” Presenter: Dr. Emiliano Trias, lead investigator of the Neurodegeneration Laboratory, Institut Pasteur in Montevideo, Uruguay.
Registration: FALAN 2016 registration
- 27th International Symposium on ALS/MND (Dublin 2016), Dec. 7-9, Dublin, Ireland.
Title: “Post-paralysis treatment with masitinib significantly slows down disease progression in transgenic SOD1 G93A (ALS) rats.” Presenter: Prof. Luis Barbeito.
Registration: Dublin 2016 registration