AB Science announces that new results published in the peer-reviewed Journal of Alzheimer's Disease support masitinib’s pot...
08 Juillet 2020 - 8:57AM
Paris, 08 July 2020, 9am
New results published in the peer-reviewed
Journal of Alzheimer's Diseasesupport masitinib’s potential
mode of action in Alzheimer’s Disease
AB Science SA (NYSE Euronext -
FR0010557264 - AB) today announced the publication of preclinical
study results with masitinib in Alzheimer’s disease entitled,
‘Effects of chronic masitinib treatment in APPPS1dE9 transgenic
mice modeling Alzheimer’s disease’. The preprint of this article is
accessible online from the peer-reviewed Journal of Alzheimer's
Disease [1]
https://content.iospress.com/articles/journal-of-alzheimers-disease/jad200466.
Masitinib given orally as an adjunct therapy has
previously been reported to slow down cognitive decline in patients
with Alzheimer’s disease [2] and a multicenter phase 3 study was
subsequently initiated in patients with mild to moderate
Alzheimer’s disease (NCT01872598).
The current research provides evidence
suggesting that masitinib’s therapeutic efficacy is associated with
a synapto-protective action in relation with mast cells
inhibition.
Dr Benoît Delatour, Principal Investigator of
the Alzheimer’s and Prion Diseases team at the ICM (Paris Brain
Institute, France) and senior author of the paper said, “This
research has shown that masitinib can restore normal spatial
learning performance in an animal model of Alzheimer's disease and
also promotes synaptic recovery. As such, these findings link the
previously reported positive proof-of-concept clinical data for
masitinib in Alzheimer's disease with evidence of a hitherto
unknown synapto-toxic mechanism associated with mast cells that can
be therapeutically targeted by masitinib”.
Olivier Hermine (President of the Scientific
Committee of AB Science and member of the Académie des Sciences in
France) commented, “These data suggest a novel mechanism by which
masitinib exerts a neuroprotective effect in Alzheimer's disease.
Overall, these results provide a new compelling biological
rationale for the use of masitinib in the treatment of Alzheimer’s
disease”.
- Key points from this research article include:
- The study objective was to clarify the effects of masitinib in
Alzheimer’s disease using a relevant animal model that displays
features of brain amyloid pathology, neuroinflammation, and
synaptic loss.
- Masitinib treatment restored normal spatial learning
performance of APPPS1dE9 transgenic mice.
- Masitinib promoted a recovery of synaptic markers that are
decreased in transgenic mice (similarly to patients with
Alzheimer’s disease) indicating a synapto-protective mechanism of
action.
- This effect on synaptic markers was mimicked in a mast-cell
depleted mouse model, thereby strongly implicating mast cells as a
critical therapeutic target for masitinib in Alzheimer’s
disease.
- These results represent the first reported evidence of mast
cells exerting a deleterious effect on synapses in an Alzheimer’s
disease background.
[1]
Li, Tengfei et al. ‘Effects of Chronic Masitinib Treatment in
APPPS1dE9 Transgenic Mice Modeling Alzheimer’s Disease’. 1 Jan.
2020 : 1 – 7.[2] Piette F, Belmin J, Vincent H, et al. (2011)
‘Masitinib as an adjunct therapy for mild-to-moderate Alzheimer's
disease: a randomised, placebo-controlled phase 2 trial’.
Alzheimer’s Res Ther 3, 16-16.
About masitinibMasitinib 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 ScienceFounded 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
(ticker: AB).
Further information is available on AB Science’s website:
www.ab-science.com.
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