AB Science: New research shows that masitinib limits neuronal
damage in a model of neuroimmune-driven neurodegenerative disease
PRESS RELEASE
NEW RESEARCH SHOWS THAT MASITINIB LIMITS
NEURONAL DAMAGE IN A MODEL OF NEUROIMMUNE-DRIVEN NEURODEGENERATIVE
DISEASE
THIS IS THE FIRST DEMONSTRATION THAT
MASITINIB CAN LOWER SERUM NEUROFILAMENT LIGHT CHAIN, AN IMPORTANT
BIOMARKER FOR NEURODEGENERATIVE DISORDERS
Paris, March 13, 2024, 12.45pm CET
AB Science SA (Euronext -
FR0010557264 - AB) today announced the publication of new
preclinical results for masitinib in neurodegenerative diseases
(NDD). Findings have been published on the bioRxiv preprint service
as an article entitled, ‘Masitinib limits neuronal damage, as
measured by serum neurofilament light chain concentration, in a
model of neuroimmune-driven neurodegenerative disease’. This
article is freely accessible online from the bioRxiv site [1].
The neuroprotective action of masitinib was
studied in an animal model of experimental autoimmune encephalitis
(EAE). EAE is a model of neuroimmune-driven chronic
neuroinflammation and importantly, neuronal damage, or prevention
thereof, can be rapidly assessed by measuring serum neurofilament
light chain (NfL) concentration in EAE-induced mice. Results showed
that masitinib can significantly lower serum NfL levels, and by
extension therefore, neuronal damage, in a neuroimmune-driven
neurodegenerative disease model, with concomitant reduction in
pro-inflammatory cytokines and slowing of clinical symptoms.
Patrick Vermersch, MD, Professor of Neurology at
the University of Lille, France, and co-author of this article
commented: “Using a model that is highly relevant to masitinib's
mechanism of action in neurodegenerative diseases, this research
has shown for the first time that masitinib can lower serum NfL
levels, as well as pro-inflammatory cytokines, and by extension
therefore, reduce the rate of neuronal damage. Because chronic
neuroinflammation is a common pathological characteristic of most
neurodegenerative diseases, the observed NfL treatment response
indicates that masitinib has a plausible disease-modifying activity
in diseases such as progressive multiple sclerosis, amyotrophic
lateral sclerosis (ALS) and Alzheimer's disease.”
Alain Moussy, co-founder and CEO of AB Science
said: “The ability of masitinib to impact NFL in an animal model
might be important because biomarkers are at the forefront not only
of research in neurodegenerative disorders to predict clinical
outcome but also reglementary guidelines to accelerate
registration. FDA has recognized recently NFL from patients as a
potential biomarker for ALS registration and has issued a recent
guideline in Alzheimer’s Disease encouraging the use of biomarker
for accelerated approval. AB Science is not only working on disease
biomarkers such an NFL but also on mechanistic biomarkers of the
response of masitinib.”
- Key points from this research
article include:
- Masitinib treatment significantly
limited NfL production in EAE mice with respect to the control
group, at various timepoints during the 15-day treatment period and
in a dose dependent manner.
- Masitinib significantly lowered
several well-established pro-inflammatory cytokine biomarker
concentrations in EAE mice.
- A beneficial effect of masitinib on
functional performance was also observed, with significantly less
relative deterioration in grip strength as compared with the
control group.
- The measurement of NfL in
biological fluids has been proposed for monitoring the therapeutic
effect of drugs aimed at reducing axonal damage in various NDDs,
including amyotrophic lateral sclerosis, multiple sclerosis, and
Alzheimer’s disease.
- EAE is a model of
neuroimmune-driven chronic neuroinflammation and therefore highly
relevant to masitinib's mechanism of action in NDDs.
- Data was derived after disease
onset (i.e., in a therapeutic setting as opposed to an asymptomatic
preventative setting), which is of greater relevance because such
models more closely simulate the clinical condition of NDD patients
and therefore better represent their therapeutic needs.
[1] Hermine O, Vermersch P, et al. Masitinib
limits neuronal damage, as measured by serum neurofilament light
chain concentration, in a model of neuroimmune-driven
neurodegenerative disease. Preprint. bioRxiv 2024.03.07.583695;
doi:
https://doi.org/10.1101/2024.03.07.583695https://www.biorxiv.org/content/10.1101/2024.03.07.583695v1.full.pdf+html
About the neurofilament light chain
(NfL) biomarkerThe measurement of neurofilament light
chain (NfL) in biological fluids has been proposed for monitoring
the therapeutic effect of drugs aimed at reducing axonal damage.
NfL are cytoskeletal proteins that are highly specific for neurons
in both the central nervous system (CNS) and the peripheral nervous
system. NfL in cerebrospinal fluid or the bloodstream is therefore
indicative of axonal lesions and/or degeneration and elevated NfL
levels are associated with traumatic brain injuries or
neurodegenerative diseases (NDD), including amyotrophic lateral
sclerosis, multiple sclerosis, and Alzheimer’s disease. A growing
body of literature shows that because the level of free NfL in
serum/plasma directly reflects neuronal damage within the CNS, it
can be used as a reliable and easily accessible marker of disease
intensity and/or activity across a variety of neurological
disorders.
About bioRxivbioRxiv
(pronounced "bio-archive") is a free online archive and
distribution service for unpublished preprints in the life
sciences. It is operated by Cold Spring Harbor Laboratory, a
not-for-profit research and educational institution. By posting
preprints on bioRxiv, authors are able to make their findings
immediately available to the scientific community and receive
feedback on draft manuscripts before they are submitted to
journals.
About masitinibMasitinib is a
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, inflammatory
diseases and viral 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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