MANF Therapeutics Announces
Positive MANF
Pre-Clinical Data
in
Alpha-Synuclein
Model of Parkinson's Disease
Published in Peer-Reviewed Journal
Experimental Neurobiology
New York, NY
-- July
9, 2018
-- InvestorsHub NewsWire -- MANF
Therapeutics, Inc., a wholly-owned subsidiary of
Amarantus Bioscience Holdings, Inc. (OTCPK:
AMBS) in pre-clinical development advancing mesencephalic
astrocyte-derived neurotrophic factor (MANF) as a disease-modifying
treatment for orphan ophthalmological conditions, Glaucoma and
Parkinson's disease, today announced
the publication
of a
scientific article
entitled "MANF protects dopamine neurons and locomotion
defects from a human alpha-synuclein induced
Parkinson's disease model in C. elegans by regulating ER stress and
autophagy pathways" in the peer-reviewed
journal Experimental
Neurobiology.
The authors
are researchers at Tongji University School of
Medicine and
Tongji University's School of Life Science and
Technology.
A gene therapy
approach to express MANF was used in the C. elegans Parkinson's
disease (PD) model of human alpha-synuclein. Alpha-synuclein is a protein
that is mis-folded and aggregates
in
PD,
potentially driving disease progression. The data demonstrated
that MANF restores locomotory ability
in
the disease
model, as well as restoring morphology and function
of the dopaminergic
(DA)
neurons. Taken together with previous
data demonstrating MANF's ability to regenerate DA neurons
by
restoring morphological and
chemical imbalances in neurotoxin-based
animal
models of
Parkinson's disease, MANF represents a potential disease-modifying
treatment for patients based on its
unique
mechanism of
action. Previously reported pre-clinical studies
have
demonstrated the
ability to precisely
deliver MANF protein to the brain areas associated
with Parkinson's disease via convection-enhanced delivery
(CED).
MANF Therapeutics
is preparing to restart IND-enabling development of MANF in
2018. MANF
has therapeutic potential across multiple orphan
ophthalmological conditions such as RAO and retinitis
pigmentosa,
where MANF has already received orphan drug designations from the
FDA, as well as in larger indications such as Glaucoma, Parkinson's
disease, diabetes and cardiovascular
disease, including stroke and myocardial
infarction. MANF Therapeutics is the
front-runner and primary worldwide intellectual property
(IP)
holder for
MANF-based therapies including protein therapy, gene therapy and
cell therapy. The Company owns rights to
composition of matter patents and patent applications
for
MANF
and
owns,
or has licenses
to,
method of use
patents and
patent applications covering the use of MANF in
ophthalmology, neurology and diabetes.
Citation: Experimental
Neurology, Volume 308, October 2018, Pages
59-71
Highlights
-
The degeneration of DA neurons occurs before locomotion defects
in C. elegans, MANF rescues DA neural degeneration and locomotion
defects during all the period of PD progression.
-
MANF reduces the aggregation of -synuclein, restores dopamine
levels and rescues the function of DA neurons in the -synuclein C.
elegans model of PD.
-
ER stress and autophagy pathways are involved in MANF-mediated
neuroprotection.
ABSTRACT
Many studies have
demonstrated that mesencephalic astrocyte-derived neurotrophic
factor (MANF) has been shown protective effects on
neurotoxin-based models of Parkinson's
disease (PD). It still remains
unclear whether
MANF can rescue dopaminergic (DA) neurons in an alpha-synuclein model. Glial cell
line-derived neurotrophic factor (GDNF) and its related
neurturin
(NRTN) can protect
DA neurons in the neurotoxin but not alpha-synuclein animal models of PD,
it failed in the clinical trials. Since alpha-synuclein model can better
mimic the progression of human PD, in our study we overexpressed
MANF specifically in DA neurons by using an alpha-synuclein Caenorhabditis
elegans (C. elegans) model. Our results showed MANF alleviated
progressive neuronal degeneration and prevented locomotion defects.
Indeed, MANF can protect cilia of DA neurons at an early stage,
suggested that MANF participated in the whole process of neuronal
degeneration. Furthermore, we found MANF facilitated the removal of
misfolded alpha-synuclein proteins and rescued
the function of damaged DA neurons. By using RNAi approach, we
inhibited ER stress and autophagy related genes and effects of MANF
were decreased, which demonstrated ER stress and autophagy pathways
were involved in the MANF-mediated neuroprotection. Our study
suggests MANF exhibits potential as a neuroprotective agent for PD
therapy.
About Parkinson's Disease
Parkinson's
disease (PD) is a chronic, progressive
neurodegenerative disorder that causes motor symptoms such as
tremors, rigidity and slowed movements as well as non-motor
symptoms including cognitive impairment, mood disorders and
autonomic dysfunction. The Parkinson's Disease Foundation estimates
that there are approximately one million people living with
Parkinson's disease in the United States and seven to 10 million PD
patients worldwide. The most commonly prescribed treatments for
Parkinson's disease are levodopa-based therapies. In the body,
levodopa is converted to dopamine to replace the dopamine loss
caused by the disease. As dopamine neurons in the brain are lost,
the therapeutic efficacy of levodopa attenuates and patients are left with
limited treatment options. A therapy that could fundamentally alter
the rate of decline, or potentially regenerate, declining
dopaminergic neurons would represent a major medical breakthrough
in the management of patients with Parkinson's disease.
About MANF Therapeutics, Inc.
MANF
(mesencephalic-astrocyte-derived neurotrophic factor) is believed
to have broad potential because it is a naturally-occurring protein
produced by the body to reduce/prevent
apoptosis (cell
death) in response to injury or disease, via the unfolded protein
response. By administering exogenously produced
MANF
to the body,
Amarantus is seeking to use a regenerative medicine approach to
assist the body with higher quantities of MANF when needed.
Amarantus is the front-runner and primary holder of intellectual
property around MANF and is initially focusing on the development
of MANF-based protein therapeutics.
MANF's lead
indication is retinitis pigmentosa, and additional indications
including Parkinson's disease, diabetes and Wolfram's syndrome are
envisioned.
Further applications for MANF may include Alzheimer's disease,
traumatic brain injury, myocardial infarction, antibiotic-induced
ototoxicity
and certain other orphan diseases.
In April
2017, Amarantus incorporated the wholly-owned subsidiary MANF
Therapeutics, Inc. to focus on progressing preclinical and clinical
development of MANF.
About Amarantus Bioscience Holdings, Inc.
Amarantus
Bioscience Holdings (AMBS) is a JLABS alumnus
biotechnology company developing treatments and
diagnostics for diseases in the areas of
neurology,
regenerative medicine and orphan diseases through its subsidiaries.
AMBS' wholly-owned subsidiary Elto Pharma,
Inc. has
development rights to eltoprazine, a Phase 2b-ready small molecule
indicated for Parkinson's disease levodopa-induced dyskinesia,
Alzheimer's aggression and adult attention deficit hyperactivity
disorder, commonly known as ADHD. AMBS acquired the rights to the
Engineered Skin Substitute program, a regenerative medicine-based
approach for treating severe burns with full-thickness autologous
skin grown in tissue culture that is being pursued by AMBS'
wholly-owned subsidiary Cutanogen
Corporation.
AMBS' wholly-owned subsidiary MANF Therapeutics, Inc. owns key
intellectual property rights and licenses from a number of
prominent universities related to the development of the
therapeutic protein known as mesencephalic astrocyte-derived
neurotrophic factor ("MANF"). MANF Therapeutics,
Inc. is
developing MANF-based products as treatments for brain and
ophthalmic disorders. MANF was discovered by the Company's Chief
Scientific Officer John Commissiong, PhD. Dr. Commissiong
discovered MANF from AMBS' proprietary discovery engine
PhenoGuard. The Company also re-acquired
rights to the Alzheimer's blood diagnostic
LymPro Test , MSPrecise and NuroPro. AMBS also owns approximately
109 million shares of Avant Diagnostics.
For further information please
visit www.Amarantus.com, or connect with the Amarantus
on Facebook,LinkedIn,Twitterand Google+.
Amarantus Investor and Media
Contact:
Howard
Gostfrand
American Capital
Ventures, Inc.
Office:
305-918-7000
Email:
hg@amcapventures.com
Source: Amarantus
Bioscience Holdings, Inc.