Neurogene Announces Presentation of Preclinical Data for Gene Therapies to Treat AGU and CMT4J, Two Rare and Devastating Neurodegenerative Disorders

Researchers present “proof of concept” data in mice at the
TM 2019

, a company with a mission to bring life-changing medicines to
patients and families affected by rare neurological diseases, today
announced that researchers presented preliminary, unpublished “proof of
concept” data in mice evaluating the safety and efficacy of
adeno-associated virus (AAV) gene therapy for AGU and CMT4J, two rare
neurological diseases, at the 15th Annual WORLDSymposiumTM
conference in Orlando, Florida.

The potential therapies are being investigated under a collaboration
agreement between Neurogene and UT Southwestern Medical Center through
multiple sponsored agreements. Neurogene provides financial support for
these and other related research projects, including pre-clinical
studies for AGU and CMT4J.

AAV gene therapy is being investigated as a potential treatment for
aspartylglucosaminuria (AGU), a neurodegenerative disease caused by
dysfunction of the AGA gene. The unpublished data, which have not been
peer reviewed, consider the safety and efficacy of gene therapy for
these diseases in mice in support of potential future clinical trials.
Xin Chen, Ph.D., Instructor of Pediatrics at UT Southwestern Medical
Center, presented data evaluating the effects in mice lacking a
functional AGA gene, using intravenous or intrathecal administration
with low and high doses, and data were reported for early symptomatic
mice. Dr. Chen’s team reported data indicating AGU gene therapy resulted
in dose-dependent, complete or near-complete elimination of toxic
substrate in central and peripheral tissues and body fluids and that
treatment was well-tolerated at supraphysiological levels.

Cathleen “Cat” Lutz, Ph.D., MBA, from the independent, nonprofit
biomedical research institution The Jackson Laboratory (JAX), assessed
the efficacy and safety profile of an AAV gene therapy product for the
treatment of Charcot-Marie-Tooth disease, type 4J (CMT4J) syndrome, a
debilitating peripheral neuropathy caused by dysfunction of the FIG4
gene. CMT4J gene therapy resulted in a dose-dependent, significant
improvement in survival, gross motor function, nerve conduction
velocity, and histopathology, with optimal outcomes in mice dosed with a
maximally feasible dose and at younger ages before significant cellular
damage had occurred. There were no observable unexpected adverse effects
reported from overexpressing FIG4 in knockout or wildtype mice.

“Results thus far for the AGU and CMT4J gene therapy programs provide
encouraging proof of principle data to support future first-in-human
clinical trials,” stated Rachel McMinn, Ph.D., President and CEO of
Neurogene. “We are working closely with our collaborators to advance
these programs as expeditiously as feasible to help families suffering
from these diseases and further our commitment to advance a pipeline of
genetic medicines to treat the underlying cause of serious neurological

About AGU

AGU is a rare neurodegenerative lysosomal storage disease caused by a
deficiency of the aspartylglucosaminidase (AGA) enzyme, which leads to
toxic accumulation of N-acetylglucosamines that ultimately cause
cellular dysfunction. AGU is characterized in childhood by developmental
delay, high rates of inner ear infections, hepatosplenomegaly,
gastrointestinal disturbance, ventral wall hernia and gate disturbance.
With disease progression, patients experience psychomotor regression,
worsening gait disturbance, behavioral and emotional issues, worsening
intellectual disability, coarsened facial features, and an increasing
risk of seizure. People with AGU have a shortened life span.
Unfortunately, AGU can go undiagnosed or misdiagnosed as autism or ADHD,
unless a specific genetic, blood or urine based test is performed.

About CMT4J

Charcot-Marie-Tooth diseases are the most common inherited motor and
sensory neuropathies, composed of a group of pathologically and
genetically distinct subtypes ranging from slowly to rapidly progressive
disease. CMT4J is a rare form of CMT caused by mutations in the FIG4
gene, which leads to uneven loss of myelin of sensory and motor nerve
axons. Individuals with CMT4J typically develop symptoms in early to
late childhood, presenting with leg weakness, muscle atrophy and
clumsiness, and early onset disease is associated with a rapidly
progressive course, ultimately leading to loss of ambulation,
quadriplegia, respiratory compromise and premature death. Later onset
disease has a more variable course that can lead to transient muscle
weakness for some patients, while others develop a rapidly progressive
form of the disease that is reminiscent of amyotrophic lateral
sclerosis. CMT4J may be misdiagnosed as chronic inflammatory
demyelinating polyneuropathy, Guillain-Barre Syndrome, or other
neuromuscular disorders.

About Neurogene, Inc.

Neurogene was founded to bring life-changing medicines to patients and
families affected by rare neurological disorders. We partner with
leading academic researchers, patient advocacy organizations and
caregivers to bring therapies to patients that address the underlying
genetic cause of a broad spectrum of neurological diseases where no
effective treatment options exist today. Our lead programs use AAV-based
gene therapy technology to deliver a normal gene to patients with a
dysfunctional gene. Neurogene is also investing in novel technologies to
develop treatments for diseases not well served by gene therapy. For
more information, visit

Neurogene is collaborating with UT Southwestern Medical Center through
multiple sponsored agreements. Neurogene provides financial support for
these and other related research projects including pre-clinical studies
for AGU and CMT4J.


Sara Green, Ten Bridge Communications

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