TIDMPRTC
PureTech Health PLC
28 April 2021
28 April 2021
PureTech Health plc
PureTech Announces Nature Publication Supporting Modulation of
Meningeal Lymphatics to Target Alzheimer's Disease Pathologies
Preclinical research suggests that restoring lymphatic flow in
the brain has the potential to address a range of neurodegenerative
diseases, such as Alzheimer's and Parkinson's diseases, and
associated neuroinflammation
Additionally, research found that improving lymphatic flow could
enhance the efficacy of antibody therapies against aberrant
proteins, potentially opening a new avenue for disease
management
PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the
"Company"), a clinical-stage biotherapeutics company dedicated to
discovering, developing and commercializing highly differentiated
medicines for devastating diseases, today announced the publication
of preclinical research in Nature which suggests that enhancing
meningeal lymphatic drainage could improve clinical outcomes for
Alzheimer's disease, either alone or in combination with passive
immunotherapies such as antibodies directed at amyloid beta
(A<BETA>). The paper also uncovered a link between
dysfunctional meningeal lymphatics and damaging microglia
activation in Alzheimer's disease, suggesting another route by
which restoring healthy drainage patterns could improve clinical
outcomes.
PureTech holds an exclusive license to the underlying
intellectual property and is advancing this work via its
wholly-owned meningeal lymphatics research program. Through this
program, PureTech aims to advance novel therapeutic approaches to
modulate lymphatic flow in the central nervous system (CNS) for the
potential treatment of a range of neurodegenerative and
neuroinflammatory diseases.
This research was led by PureTech collaborator Jonathan Kipnis,
Ph.D., the Alan A. and Edith L. Wolff Distinguished Professor of
Pathology and Immunology and a BJC Investigator at Washington
University School of Medicine in St. Louis, and Sandro Da Mesquita,
Ph.D., Assistant Professor of Neuroscience at Mayo Clinic, in
collaboration with PureTech scientists. Dr. Kipnis's lab pioneered
the identification, characterization and understanding of the
meningeal lymphatics , which connect the brain to the immune
system, and has published several groundbreaking papers elucidating
the system's role in clearing waste from the CNS to modulate
neurological health. The new paper builds on foundational research
published in Nature in 2018, in which Dr. Kipnis's lab showed that
disrupting meningeal lymphatic drainage promoted A<BETA>
accumulation in preclinical models of Alzheimer's disease. His most
recent work finds that improving meningeal lymphatic drainage
enhances A<BETA> clearance in conjunction with passive
immunotherapies and modulates microglia activation to improve
neural tissue homeostasis in aged transgenic Alzheimer's disease
mice.
"Step by step, we have illuminated the crucial role the
meningeal lymphatics system plays in maintaining neurological
health. With these recent findings, we have taken an important leap
forward by demonstrating the potential to improve clinical outcomes
by restoring lymphatic flow in the brain," Dr. Kipnis said. "These
foundational findings in preclinical Alzheimer's models are
exciting because they point the way to potential therapeutics in an
area where the need is profound and devastating. I look forward to
continuing to collaborate with the team at PureTech as we seek to
apply these and other findings to the development of new treatments
for neurodegenerative and neuroinflammatory conditions."
Protein clumping in the brain, including aggregates of
A<BETA>, tau and alpha synuclein, are a well-known hallmark
of major neurodegenerative disorders, among them Alzheimer's
disease and Parkinson's disease. Antibodies have been developed to
target these clumps of aberrant proteins, but these treatments
historically have shown limited clinical efficacy. Working with
transgenic Alzheimer's disease mice, Dr. Kipnis and his team found
that deterioration of lymphatic vascular in the dorsal meninges was
correlated with a significant increase in A<BETA> throughout
all analyzed regions of the brain. Further analysis suggested that
reduced lymphatic drainage may lead to improper activation of
microglia, diminishing their ability to process and present
antigens to adaptive immune cells and potentially impairing
efficacy of passive immunotherapies such as a
A<BETA>-targeting antibodies. Dr. Kipnis found that
A<BETA> clearance improved markedly when the therapeutic
antibodies were injected directly into the cerebrospinal fluid
(CSF) of transgenic Alzheimer's disease mice that had been treated
with viral-mediated mVEGF-C to enhance meningeal lymphatic
drainage. The new research suggests that improving lymphatic flow
could enhance the efficacy of antibody therapies, especially those
administered directly to the CSF, opening a new avenue for disease
management.
"This new research reinforces our belief that modulating the
meningeal lymphatics system may be a key to treating not just
Alzheimer's disease, but other neurological disorders as well,"
said Joseph Bolen, Ph.D., Chief Scientific Officer at PureTech
Health. "We are proud to be working with Dr. Kipnis, a true
scientific pioneer, to advance therapeutic discovery programs
leveraging these findings. We hope to make a real difference to
patients by bringing these foundational discoveries about brain
biology to life."
About the Meningeal Lymphatics Research Program
PureTech is exploring multiple ways of altering lymphatic flow,
both in the CNS and other parts of the body. The CNS was previously
thought to be devoid of lymphatic vasculature; however, research
published in Nature in 2015 identified the meningeal lymphatic and
glymphatic systems as key maintenance organs within the brain. The
biological crosstalk at the CNS-immune interface has been further
supported by evidence published as the cover story in Nature in
2018, which demonstrated that modulation of lymphatic function in
the brain may potentially prevent or delay diseases associated with
neurodegeneration, including Alzheimer's disease, Huntington's
disease and age-associated cognitive decline. This CNS-immune
interface has also been supported by evidence published in Nature
Neuroscience in 2018, which identifies a direct connection between
the CSF and the meningeal lymphatic system, suggesting that
modulation of the meningeal lymphatic vessel network has the
potential to ameliorate symptoms in CNS disorders, such as multiple
sclerosis. These insights underlie PureTech's approach to designing
novel categories of therapeutics to address debilitating and
devastating CNS disorders, and the related intellectual property
has been exclusively licensed to PureTech.
About PureTech Health
PureTech is a clinical-stage biotherapeutics company dedicated
to discovering, developing and commercializing highly
differentiated medicines for devastating diseases, including
inflammatory, fibrotic and immunological conditions, intractable
cancers, lymphatic and gastrointestinal diseases and neurological
and neuropsychological disorders, among others. The Company has
created a broad and deep pipeline through the expertise of its
experienced research and development team and its extensive network
of scientists, clinicians and industry leaders. This pipeline,
which is being advanced both internally and through PureTech's
Founded Entities, is comprised of 26 therapeutics and therapeutic
candidates, including two that have received FDA clearance and
European marketing authorization, as of the date of PureTech's most
recently filed Annual Report on Form 20-F. All of the underlying
programs and platforms that resulted in this pipeline of
therapeutic candidates were initially identified or discovered and
then advanced by the PureTech team through key validation points
based on the Company's unique insights into the biology of the
brain, immune and gut, or BIG, systems and the interface between
those systems, referred to as the BIG Axis.
For more information, visit www.puretechhealth.com or connect
with us on Twitter @puretechh.
Cautionary Note Regarding Forward-Looking Statements
This press release contains statements that are or may be
forward-looking statements, including statements that relate to the
company's future prospects, developments, and strategies. The
forward-looking statements are based on current expectations and
are subject to known and unknown risks and uncertainties that could
cause actual results, performance and achievements to differ
materially from current expectations, including, but not limited
to, our expectations regarding the potential therapeutic benefits
of our therapeutic candidates, our expectations regarding the
meningeal lymphatics research program and the potential therapeutic
benefits based on our published preclinical findings including the
potential for treatment in a range of neurodegenerative and
neuroinflammatory diseases and those risks and uncertainties
described in the risk factors included in the regulatory filings
for PureTech Health plc. These forward-looking statements are based
on assumptions regarding the present and future business strategies
of the company and the environment in which it will operate in the
future. Each forward-looking statement speaks only as at the date
of this press release. Except as required by law and regulatory
requirements, neither the company nor any other party intends to
update or revise these forward-looking statements, whether as a
result of new information, future events or otherwise.
Contact:
Investors EU media U.S. media
Allison Mead Talbot Ben Atwell, Rob Winder Stephanie Simon
+1 617 651 3156 +44 (0) 20 3727 1000 +1 617 581 9333
amt@puretechhealth.com ben.atwell@FTIconsulting. stephanie@tenbridgecommunications.
com com
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