Full Press Release Details
VistaGen Announces Positive
Preclinical Data Supporting AV-101's
Potential for Treating Levodopa-Induced Dyskinesia in Patients with
Parkinson's Disease, without the Psychological Side Effects
and Safety Concerns of Amantadine
Significant reduction of levodopa-induced dyskinesia by AV-101
observed in gold standard MPTP non-human primate
model of Parkinson's disease, while maintaining
antiparkinsonian activity of levodopa and without causing
amantadine-like adverse effects
SOUTH SAN FRANCISCO, Calif., June 20, 2019 - VistaGen
Therapeutics (NASDAQ: VTGN), a clinical-stage
biopharmaceutical company committed to developing new generation
medicines for central nervous system (CNS) diseases and disorders
with high unmet need, today announced positive results of recent
preclinical studies of the effects of AV-101, its oral NMDA
receptor glycine site antagonist, in a widely-used MPTP non-human
primate model for reproducing motor complications of
Parkinson's disease (PD), including dyskinesia (sudden
uncontrolled movements) observed in PD patients treated with
levodopa. In the MPTP primate model, AV-101's antidyskinetic
effects were similar to those generally observed with amantadine
therapy, but AV-101 did not cause adverse effects experienced with
The MPTP primate model used in this study is the gold
standard for animal modeling of PD and has been used
extensively to study both antiparkinsonian therapies and
levodopa-induced dyskinesia (LID). MPTP is a neurotoxin that kills
dopaminergic neurons in the striatum, producing motor symptoms
similar to those of PD. In this study, AV-101's efficacy
against LID was measured through behavioral scores on a dyskinesia
scale, and a Parkinsonian disability scale was used to measure
levodopa antiparkinsonian efficacy. This study demonstrated
that AV-101 significantly (p = 0.01) reduced LID without affecting
the timing, extent, or duration of the therapeutic benefits of
levodopa. This new preclinical study was conducted by Dr. Th r se
Di Paolo, Professor in the Faculty of Pharmacy at Laval
University and among the world's leading researchers focused
on Parkinson's disease and LID, pursuant to VistaGen's
research agreement with
Qu bec Universit Laval Research Center in
Summary results of the study will be presented at an upcoming
scientific conference.
antidyskinetic activity of AV-101 that we
measured compares favorably with
our observation with amantadine in
parkinsonian monkeys, said Dr. Di Paolo. Better
than amantadine, with its known side effects (in humans with
Parkinson's disease and in parkinsonian monkeys), we
observed no adverse effects with AV-101.
pivotal pathological hallmark of PD is a loss of dopamine neurons
in the substantia nigra.
Loss of dopamine neurons is thought to be due to neurotoxicity
associated with misfolding of proteins and is associated with
increased signaling of glutamate, the most abundant excitatory
neurotransmitter in the brain. Increased glutamate activity is
involved with aberrant neuronal signaling and excitotoxic death of
NMDA receptor plays a major role in glutamatergic signaling and has
been shown to be a therapeutic target for LID, said
VistaGen's Chief Scientific Officer. AV-101's
active metabolite, 7-Cl-KYNA, is a potent and selective NMDA
receptor glycine site antagonist with neuroprotective properties.
These recent results confirm our prior antidyskinesia study in this
MPTP monkey model. We believe these preclinical data and
AV-101's positive safety profile in all clinical studies to
date support AV-101's potential to treat LID, while both
maintaining the antiparkinsonian benefits of levodopa and without
causing hallucinations or other serious side effects that may be
associated with current amantadine-based therapy for LID,
added Dr. Snodgrass.
About Parkinson's Disease
PD is the second most common neurodegenerative disease worldwide,
affecting approximately one million people in the U.S. and ten
million people worldwide, according to the Parkinson's
Foundation. Although there is no "one-size-fits-all
description of PD, PD is a complex neurodegenerative disorder that
occurs when brain cells that make dopamine, a chemical that
coordinates movement, stop working or die, resulting in progressive
deterioration of voluntary motor control. Classic PD motor symptoms
include muscular rigidity, resting tremor, and postural and gait
impairment. Typically, PD patients present with a combination of
motor and non-motor symptoms. Non-motor symptoms may include
cognitive impairment, sleep disorders, pain and fatigue. There is
currently no medication to slow, delay, stop or cure PD, and
currently available treatments are symptomatic. Treatment of motor
symptoms with oral levodopa, introduced about 50 years ago, remains
the gold standard treatment.
About Levodopa-Induced Dyskinesia
LID is a disorder that affects people with PD who are treated with
the current standard of care, oral levodopa, for an extended period
of time. Oral levodopa remains the most effective therapy for motor
symptoms of PD. However, after continuous long-term use (longer
than five years), many PD patients experience LID. Although
clinical manifestations of LID are heterogenous, LID is commonly
associated with abnormal involuntary movements, including chorea
and dystonia. These motor complications tend to become more severe
as PD progresses and as the duration of levodopa treatment is
extended, until the impact of LID may compromise the advantage of
treatment with levodopa. PD treatment with levodopa is routinely
delayed due to concerns over LID. Once LID develops,
levodopa-treated PD patients may be faced with a choice between