27 Sep 2005(Medicalnews.com) - Neurologix's Phase I trial showed
positive interim results in patients with Parkinson's disease. One
year following treatment, patients exhibited a statistically
significant improvement in motor function on the side of their body
correlating to the treated part of the brain. Further, PET scans at
one year revealed that the treated side of the brain exhibited a
statistically significant decrease in abnormal metabolism, results
considered similar to those achieved with STN Deep Brain Stimulation.
Neurologix, Inc. (OTCBB:NRGX) today announced positive interim
results of its landmark gene therapy clinical trial for patients with
Parkinson's disease. Neurologix's 12-patient, dose-escalating Phase I
trial is the world's first study to use a viral vector (the non-
pathogenic adeno-associated virus, or AAV) for the treatment of an
adult neurological disease. In the Neurologix-funded trial, the
vector was injected into a specific target site in the brain in order
to transfer a gene to treat Parkinson's disease. The gene encodes
glutamic acid decarboxylase (GAD), an enzyme which synthesizes the
major inhibitory neurotransmitter in the brain, (gamma)-aminobutyric
acid (GABA).

Under the FDA-sanctioned trial protocol, patients with advanced
Parkinson's disease received unilateral (one side of the brain)
infusion of AAV-GAD via a hair-thin catheter into the subthalamic
nucleus (STN), a deep brain structure known to function abnormally in
Parkinson's patients. According to the interim findings, Neurologix's
STN AAV-GAD treatment appears to be safe and well-tolerated in
advanced Parkinson's disease, with no evidence of adverse effects or
immunologic reaction related to the study treatment. Furthermore,
patients in the trial, at one year, exhibited a statistically
significant improvement (27%, p = .04) in motor function on the side
of their body correlating to the treated part of the brain, as
measured by the Unified Parkinson Disease Rating Scale (UPDRS). In
contrast, the untreated side evidenced no significant improvement in
the UPDRS score. Also, activities of daily living (ADL), another
standard measure of Parkinson's severity which is recorded by the
patients themselves, showed a strong trend toward statistical
improvement (p= .06).

In addition, fluorodeoxyglucose (FDG)-PET scans at one year revealed
that the treated side of the brain exhibited a statistically
significant decrease in abnormal metabolism, while the untreated side
showed a further increase in abnormal metabolism. The imaging results
were considered similar to those achieved with STN Deep Brain
Stimulation, an FDA-approved treatment which currently represents the
preferred surgical approach for advanced Parkinson's disease. This
data provides solid biological support for the observed clinical
improvements.

Twelve subjects in total have undergone gene transfer, four in each
of three dose cohorts. Seven of the eight patients representing the
low and mid-dose cohorts have now been evaluated one year following
treatment. Three of the remaining five subjects have been followed
for six months and the remaining two for more than four months.

The Phase I trial, which is the first FDA-approved clinical trial to
test gene therapy to treat Parkinson's disease, is an open-label dose-
escalation study with four patients in each of three escalating dose
cohorts. The third cohort of four patients received 10 times the dose
of the first cohort. The 12 patients participating in the trial were
diagnosed with severe Parkinson's disease of at least five years'
duration and no longer adequately responded to current medical
therapies.

The Gene Therapy Procedure

The surgery entailed a stereotactic neurosurgical procedure performed
under local anesthesia with the patient awake. First, MRI was used to
image the target subthalamic nucleus (STN) region of the brain. The
STN was mapped using microelectrodes by recording from single neurons
as the electrode was slowly moved towards the STN. Once a signature
firing pattern was obtained confirming that the electrode was in the
STN, the fine-wire electrode was removed, leaving only the
microelectrode sheath through which a hair-thin (165 micron) hollow
tube was inserted. Thirty-five microliters containing 3.5, 10 or 35
billion particles (depending upon dose cohort) of the AAV (adeno-
associated virus) viral vector with a human GAD gene (cDNA) were then
infused at 0.5 microliters/minute, together with 15 microliters of
25% mannitol. After the 100-minute infusion period, the delivery
catheter was withdrawn and the incision closed. No hardware was left
behind following this procedure, and all patients were discharged
within 48 hours of the procedure.