MELBOURNE, Australia,
Jan. 28, 2022 /PRNewswire/
-- Alterity Therapeutics (ASX: ATH, NASDAQ: ATHE) ("Alterity"
or "the Company"), a biotechnology company dedicated to developing
disease modifying treatments for neurodegenerative
diseases, today announced that data in an animal model of
Multiple System Atrophy (MSA) were published in the Journal of
Parkinson's Disease. MSA is a
devastating neurodegenerative disorder without approved
therapy.
The publication, entitled, "The Compound ATH434
Prevents Alpha-Synuclein Toxicity in a Murine Model of
Multiple System Atrophy" describes a study evaluating the efficacy
of ATH434 in genetically altered mice that develop manifestations
of MSA. The investigation demonstrated that in the studied
brain region, ATH434 treatment reduced both the toxic oligomeric
and aggregated forms of α–synuclein, a central nervous system
protein important for normal function of nerve cells. At the same
time, ATH434 treatment reduced the cardinal pathology of MSA (glial
cell inclusions), reduced brain iron, preserved neurons and
improved motor performance. The publication concluded that ATH434
is a promising small molecule drug candidate that has potential for
treating MSA. The study was led by David I.
Finkelstein, Ph.D., Head of Parkinson's Disease Laboratory
at the Florey Institute of Neuroscience and Mental Health and the
University of Melbourne. The full
publication can be accessed here.
"These preclinical data are extremely valuable as they
demonstrate our thesis that by binding and redistributing excess
iron in the brain of patients with Parkinsonian disorders, we can
reduce α–synuclein aggregation and oxidative stress and rescue
neurons in multiple brain regions to address the underlying
pathology of disease," said David
Stamler, M.D., Chief Executive Officer, Alterity. "We
believe that these preclinical studies may translate to clinical
benefit in patients with MSA, and we look forward to further
patient evaluation in our upcoming Phase 2 clinical trial."
Elevation in regional brain iron together with accumulation of
aggregated α–synuclein are important contributors to the pathology
of MSA. Previous studies with ATH434 in preclinical models of
Parkinson's disease have shown that it is brain-penetrant, reduces
iron accumulation and iron-mediated redox activity, provides
neuroprotection, inhibits α–synuclein aggregation and improves
motor function. The compound was also well-tolerated in a
first-in-human oral dosing study in healthy and older adult
volunteers with a favorable, dose-dependent pharmacokinetic
profile.
In this study, genetically altered, or transgenic, mice
overexpress α–synuclein, develop glial cell inclusions, and
manifest motor and non-motor aspects of MSA. Animals received
ATH434 in food or a control diet for 4 months starting at 12 months
of age. Western blot analysis was used to assess oligomeric and
aggregated forms of α-synuclein levels in brain and stereology was
used to quantitate the number of neurons and glial cell inclusions
in the substantia nigra pars compacta.
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 Multiple System Atrophy
Multiple System Atrophy (MSA) is a rare, neurodegenerative
disease characterized by failure of the autonomic nervous
system and impaired 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 a variable combination of slowed movement and/or
rigidity, 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 glia, 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
1National
Institute of Health: Neurological Disorders and Stroke, Multiple
System Atrophy Fact Sheet
|
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 Parkinsonian
disorders. Alterity also has a broad drug discovery platform
generating patentable chemical compounds 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