Paris, March 21, 2019, 6.30pm
AB Science Announces Acceptance of Abstract for Oral Presentation at the 2019 Muscular Dystrophy Association Conference
Data Provides Further Evidence on Masitinib`s Mode of Action in ALS via Modulation of the Degenerative Neuronal Microenvironment
AB Science SA (NYSE Euronext - FR0010557264 - AB), a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), announced today that new preclinical data for masitinib in amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig`s disease, will be presented at the 2019 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference (Orlando, FL, USA, April 13th - 17th).
This research, which comes from the laboratory of Professor Luis Barbeito (Head of the Neurodegeneration Laboratory, Institut Pasteur in Montevideo, Uruguay), will be delivered during an oral session on `Inflammation, Immune Mechanisms, & Therapeutic Approaches` on Tuesday, 16th April (8am - 10am). The title of this 25-minute platform presentation is "Post-paralysis treatment with masitinib ameliorates peripheral nerve pathology driven by macrophages, mast cells and neutrophils in an inherited model of ALS".
Findings which will be detailed during the conference have revealed a novel mechanism of neurogenic inflammation from damaged motor neurons and non-neuronal cells, which can be therapeutically modulated by masitinib.
Together with previously published evidence in prominent peer-reviewed journals1,2,3, which showed that masitinib effectively co-targets independent pathological mechanisms in different cell types of the brain and spinal cord, these data provide additional insight into masitinib`s mode of action and further validate its potential as a new treatment option for ALS.
The 2019 MDA Clinical & Scientific Conference is the most comprehensive neuromuscular disease meeting in the United States, representing the full spectrum of scientific researchers, medical professionals, and decision makers.
- Reminder of key findings from previously published preclinical studies1,2,3
- It has been demonstrated that mast cells infiltrate and degranulate into skeletal muscle of ALS patients to a significantly greater degree than is seen in control samples.
- Neutrophils infiltrate into the degenerating skeletal muscle of ALS patients and interact with mast cells and neuromuscular junctions.
- These findings in ALS patients are in accordance with analyses in muscle from SOD1G93A rats, where paralysis progression is known to correlate with degranulating mast cells.
- Masitinib, administered after paralysis onset, significantly reduced mast cell and neutrophil accumulation and motor pathway degeneration.
- Preclinical data derived from human ALS patients supports relevance of past animal data to human pathology.
- Masitinib treatment significantly prolonged survival in post-paralytic SOD1G93A rats.
- Disease progression in this animal model of ALS was accompanied by massive infiltration and accumulation of mast cells around degenerating motor axons and neuromuscular junctions. This correlated with paralysis progression, suggesting mast cells may be deleterious for the maintenance of functional neuromuscular junctions.
- Masitinib-induced mast cell reduction significantly reduced the rate of neuromuscular junction denervation, progression of motor deficits, and prevented morphological changes in Schwann cells and capillary networks that are typically observed in advanced paralysis.
- Immunohistochemistry data showed that masitinib treatment modulated microglia activity improving microgliosis and motor neuron pathology.
 Trias E, et al. Mast cells and neutrophils mediate peripheral motor pathway degeneration in ALS. JCI Insight. JCI Insight. 2018;3(19):e123249. https://doi.org/10.1172/jci.insight.123249.
 Trias E, et al. Evidence for mast cells contributing to neuromuscular pathology in an inherited model of ALS. JCI Insight. 2017;2(20):e95934. https://doi.org/10.1172/jci.insight.95934.
 Trias E, et al. Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis. J Neuroinflammation. 2016;13(1):177.
Masitinib is a new orally administered tyrosine kinase inhibitor that targets mast cells and macrophages, important cells for immunity, through inhibiting a limited number of kinases. Based on its unique mechanism of action, masitinib can be developed in a large number of conditions in oncology, in inflammatory diseases, and in certain diseases of the central nervous system. In oncology due to its immunotherapy effect, masitinib can have an effect on survival, alone or in combination with chemotherapy. Through its activity on mast cells and microglia and consequently the inhibition of the activation of the inflammatory process, masitinib can have an effect on the symptoms associated with some inflammatory and central nervous system diseases and the degeneration of these diseases.
About AB Science
Founded in 2001, AB Science is a pharmaceutical company specializing in the research, development and commercialization of protein kinase inhibitors (PKIs), a class of targeted proteins whose action are key in signaling pathways within cells. Our programs target only diseases with high unmet medical needs, often lethal with short term survival or rare or refractory to previous line of treatment.
AB Science has developed a proprietary portfolio of molecules and the Company`s lead compound, masitinib, has already been registered for veterinary medicine and is developed in human medicine in oncology, neurological diseases, and inflammatory diseases. The company is headquartered in Paris, France, and listed on Euronext Paris (AB.PA).
Further information is available on AB Science`s website: www.ab-science.com.
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Source: AB Science via GlobeNewswire