Long-term Results of GDNF Pilot Trial; Gene Therapy in Animal Model (AAN 2004)

[Linda J Herman <ljherman1@xxxxxxxx>]

FROM: E-MOVE:

Two encouraging reports--

Long-term Results of GDNF Pilot Trial (AAN 2004)
E-MOVE reports from the American Academy of Neurology, San Francisco
April 25-30, 2004. Page (A), session (S) and poster (P) numbers are from
Neurology 2004;62(7), Suppl 5

The long term effect of glial derived neurotrophic factor infusions and
18F-dopa uptake in Parkinson?s disease
GR Hotton, NK Patel, SS Gill, P Heywood, CJ Svendson, DJ Brooks
S38.001; A345

GDNF improves PD symptoms and increased fluorodopa uptake in the putamen
for up to two years, according to this report.

Five patients received GDNF bilaterally (n=4) or unilaterally (n=1) via
implanted minipump and indwelling cannula to the posterior putamen for
two years. UPDRS total score and ADL score improved by 41% versus
baseline, with most of the improvement occurring during the first 12
months. Fluorodopa uptake increased by 6o% in the posterior putamen, but
by only 6% in the anterior putamen, away from the site of the cannula.

Six-month results of this trial were reported by E-MOVE and are archived
at 

A double-blind trial of GDNF is currently underway, with results expected
to be announced in the fall of 2004.
------------------------------------------------------------------
Long-term Effectiveness of AADC Gene Therapy in PD Monkeys (AAN 2004)
E-MOVE reports from the American Academy of Neurology, San Francisco
April 25-30, 2004. Page (A), session (S) and poster (P) numbers are from
Neurology 2004;62(7), Suppl 5

Long-term evaluation of AAV/AADC gene transfer in parkinsonian monkeys
K Bankewiecz, M Daadi, R Danchez-Pernaute, P Pivirotto, J Bringas, P
Herscovitch, R Carson, W Eckelman, J Cunningham, JL Eberling
S28.004; A258

Gene therapy with aromatic acid dopa decarboxylase (AADC) remains stable
for up to 4 years, and reduces levodopa requirement in parkinsonian
monkeys, according to this study. AADC converts levodopa into dopamine;
the natural reservoir of AADC in dopaminergic neurons is depleted during
the course of Parkinson?s disease.

MPTP-treated monkeys received unilateral injection to the striatum of
AADC carried on an adeno-associated virus vector, or non-therapeutic
control vector. Fluorodopa PET imaging indicated an approximately
five-fold increase in uptake in the striatum; despite focal injection,
the increase in the imaging marker was largely uniform throughout the
striatum. AADC-treated monkeys ?showed clinical recovery and a robust
response? to previously non-therapeutic doses of levodopa ?without any
side effects,? according to the authors. Results remained stable for up
to 4 years.

The authors conclude, ?This approach may have direct application for
treating PD by restoring and/or increasing striatal conversion rates of
systemically administered levodopa, thus widening the therapeutic window
and may help to avoid levodopa-induced dyskinesias.?

----------------------------------------------------------------------
To sign-off Parkinsn send a message to: mailto:listserv@xxxxxxxxxxxxxxxxxxxx
In the body of the message put: signoff parkinsn