MELBOURNE,
Australia, Nov. 4, 2021
/PRNewswire/ -- Alterity Therapeutics (ASX: ATH, NASDAQ: ATHE)
("Alterity" or "the Company"), a biotechnology company dedicated to
developing disease modifying treatments for neurodegenerative
conditions, today announced the publication of two preclinical
studies demonstrating the potential of ATH434 to treat Parkinsonian
disorders.
Non-motor symptoms (NMS) are common in patients with
Parkinsonian disorders, such as Parkinson's disease (PD) and
Multiple System Atrophy. Parkinson's disease patients experience
gastrointestinal (GI) complications, cognitive deficits, autonomic
dysfunction, and mood disturbance and these non-motor
manifestations are an important source of morbidity and reduced
quality of life. As published in the Journal of Parkinson's
Disease, "ATH434 Reverses Colorectal Dysfunction in the A53T Mouse
Model of Parkinson's Disease" presents results from a preclinical
study investigating the effect of ATH434 on GI complications of
PD.
"This published study provides further evidence of the potential
for ATH434 to modify the course of Parkinson's disease. The
reversal of colonic dysfunction in this preclinical model of PD may
translate to clinical benefit in alleviating non-motor symptoms for
individuals living with the disease," said David Stamler, M.D., Chief Executive Officer,
Alterity. "Practicing clinicians are well aware of the substantial
impact that these symptoms have on the quality of life of
individuals with Parkinson's disease. We are currently conducting
additional preclinical studies to evaluate the potential of ATH434
for the treatment of PD and look forward to advancing it into a
future proof-of-concept study."
Common gastrointestinal complications associated with PD include
swallowing difficulty, delayed stomach emptying, slower nutrient
absorption from the gut, and chronic constipation. These
complications are thought to be caused by damage to the neurons in
the enteric nervous system due to the accumulation of
alpha-synuclein. ATH434 has been shown preclinically to reduce the
aggregation of alpha-synuclein by binding and redistributing excess
iron in areas of pathology.
In the PD animal study, ATH434 treatment was started after GI
dysfunction was established and resulted in a reversal of slowed
colonic propulsion and gut transit deficits. Importantly, the study
concluded that ATH434 can reverse some of the GI deficits and
damage to the enteric nervous system, and thus may have potential
clinical benefit in alleviating the GI complications associated
with PD.
The publication can be accessed here.
Alterity also announced the publication of an in vitro study
concluding that the novel mechanism of action of ATH434, previously
known as PBT434, provides a compelling case for its continued
development as a therapeutic agent in neurodegenerative diseases
associated with iron accumulation. As published in Plos One, the
publication, entitled, "The iron chelator, PBT434, modulates
transcellular iron trafficking in brain microvascular endothelial
cells," demonstrated that ATH434 is able to bind and redistribute
iron, thus limiting the downstream oxidative stress involved in
cytotoxic protein aggregation. Additionally, the investigation
showed that while ATH434 has moderate effects on the regulation of
iron-dependent protein expression, it does not interfere with
normal cell physiology, unlike high affinity iron chelators.
Dr. Stamler, concluded, "This study explains how ATH434 promotes
removal of excess iron from cells, thus reducing aggregation of
proteins such as α-synuclein that are implicated in the pathology
of Parkinsonian disorders. The findings are consistent with
previous research on our lead clinical asset and support our
strategy of targeting the excess iron implicated in these important
neurodegenerative diseases."
The publication can be accessed here.
About ATH434
Alterity's lead candidate, ATH434, is the first of a new
generation of small molecules designed to inhibit the aggregation
of pathological proteins implicated in neurodegeneration. ATH434
has been shown preclinically to reduce α-synuclein pathology and
preserve nerve cells by restoring normal iron balance in the brain.
In this way, it has excellent potential to treat Parkinson's
disease as well as various forms of atypical Parkinsonism such as
Multiple System Atrophy (MSA). ATH434 has successfully completed a
Phase 1 clinical trial demonstrating the agent is well tolerated,
orally bioavailable, and achieved brain levels comparable to
efficacious levels in animal models of MSA, with the objective of
restoring function in patients with MSA and other Parkinsonian
disorders.
ATH434 has been granted Orphan designation for the treatment of
MSA by the U.S. FDA and the European Commission.
About Parkinson's Disease
Parkinson's disease (PD) belongs to a group of conditions called
motor system disorders, which cause unintended or uncontrollable
movements of the body. The precise cause of PD is unknown, but some
cases are hereditary while others are thought to occur from a
combination of genetics and environmental factors that trigger the
disease. In PD, brain cells become damaged or die in the part of
the brain that produces dopamine--a chemical needed to produce
smooth, purposeful movement. The four primary symptoms of PD are
tremors, rigidity, slowing of spontaneous and automatic movement,
and impaired balance. Other symptoms may include difficulty
swallowing, chewing, or speaking; emotional changes; urinary
problems or constipation; dementia or other cognitive problems;
fatigue; and problems sleeping.[1] Nearly one million
people in the U.S. are living with PD, and more than 10 million
people worldwide are living with PD. Approximately 60,000 Americans
are diagnosed with PD each year.[2]
[1]
National Institute of Health: Neurological Disorders and Stroke,
Parkinson's Disease Information Page;
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[2]
Parkinson's Foundation
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About Multiple System Atrophy
Multiple System Atrophy (MSA) is a rare, neurodegenerative disease characterized by a combination
of symptoms that affect both the autonomic nervous system and
movement. The symptoms reflect the progressive loss of
function and death of different types of nerve cells in the
brain and spinal cord. It is a rapidly progressive disease and
causes profound disability. MSA is a Parkinsonian disorder
characterized by motor impairment, autonomic instability that
affects involuntary functions such as blood pressure
maintenance and bladder control, and impaired balance and/or
coordination that predisposes to falls. A pathological hallmark of
MSA is the accumulation of the protein α-synuclein within the
support cells of the central nervous system and neuron loss in
multiple brain regions. MSA affects approximately 15,000
individuals in the U.S., and while some of the symptoms of MSA
can be treated with medications, currently there are no
drugs that are able
to slow disease progression and there is no cure.[1]
[1]National Institute of Health: Neurological Disorders and Stroke, Multiple Systems Atrophy Fact Sheet
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About Alterity Therapeutics Limited
Alterity Therapeutics is a clinical stage biotechnology company
dedicated to creating an alternate future for people living with
neurodegenerative diseases. The Company's lead asset, ATH434, has
the potential to treat various forms of Parkinsonian disorders.
Alterity also has a broad drug discovery platform generating
patentable chemical to intercede in disease processes. The Company
is based in Melbourne, Australia,
and San Francisco, California,
USA. For further information please visit the Company's web site at
www.alteritytherapeutics.com.
Authorisation & Additional information
This announcement was authorized by David Stamler, CEO of Alterity Therapeutics Limited.
Forward Looking Statements
This press release contains "forward-looking statements"
within the meaning of section 27A of the Securities Act of 1933 and
section 21E of the Securities Exchange Act of 1934. The Company has
tried to identify such forward-looking statements by use of such
words as "expects," "intends," "hopes," "anticipates," "believes,"
"could," "may," "evidences" and "estimates," and other similar
expressions, but these words are not the exclusive means of
identifying such statements.
Important factors that could cause actual results to differ
materially from those indicated by such forward-looking statements
are described in the sections titled "Risk Factors" in the
Company's filings with the SEC, including its most recent Annual
Report on Form 20-F as well as reports on Form 6-K, including, but
not limited to the following: statements relating to the Company's
drug development program, including, but not limited to the
initiation, progress and outcomes of clinical trials of the
Company's drug development program, including, but not limited to,
ATH434, and any other statements that are not historical facts.
Such statements involve risks and uncertainties, including, but not
limited to, those risks and uncertainties relating to the
difficulties or delays in financing, development, testing,
regulatory approval, production and marketing of the Company's drug
components, including, but not limited to, ATH434, uncertainties
relating to the impact of the novel coronavirus (COVID-19) pandemic
on the company's business,
operations and employees, the ability of the Company to procure
additional future sources of financing, unexpected adverse side
effects or inadequate therapeutic efficacy of the Company's drug
compounds, including, but not limited to, ATH434, that could slow
or prevent products coming to market, the uncertainty of obtaining
patent protection for the Company's intellectual property or trade
secrets, the uncertainty of successfully enforcing the Company's
patent rights and the uncertainty of the Company freedom to
operate.
Any forward-looking statement made by us in this press
release is based only on information currently available to us and
speaks only as of the date on which it is made. We undertake no
obligation to publicly update any forward-looking statement,
whether written or oral, that may be made from time to time,
whether as a result of new information, future developments or
otherwise.
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SOURCE Alterity Therapeutics Limited