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| Immunohistochemistry for alpha-synuclein showing positive staining (brown) of an intraneural Lewy-body in the Substantia nigra in Parkinson's disease. Credit: Wikipedia |
February 22, 2016
Experts at the University of Pittsburgh School
of Medicine are leading the second arm of a clinical trial using gene therapy
to relieve the symptoms of tremor and mobility impairment in patients with
Parkinson's disease. The technique shows promise in prolonging the
effectiveness of levo-dopa, the mainstay treatment for the progressive
neurodegenerative condition, by increasing production of a key enzyme essential
to convert the drug into the neurotransmitter dopamine.
An estimated 7 to 10 million people worldwide
have Parkinson's disease, which is caused by degeneration of dopamine-producing
neurons, said Mark Richardson, M.D., Ph.D., assistant professor of neurological
surgery, Pitt School of Medicine, and director of Epilepsy and Movement
Disorders Surgery at UPMC. Levo-dopa can replace the deficient dopamine for a
while, but eventually the drug loses effectiveness, and subsequent increases in
dosage may cause disabling side effects.
"Less dopamine is made as the neurons
degenerate, and one reason is that there is a decrease in an enzyme needed to
turn levo-dopa into dopamine," said Dr. Richardson, who is the principal
investigator of the Pitt arm of the trial. "By inserting the gene for this
enzyme into cells in a specific part of the brain, we hope to make levo-dopa
treatment more effective for a longer period of time."
In the gene therapy, a harmless
virus called adeno-associated virus-2 is used to carry the gene that makes the
enzyme – aromatic L-amino acid decarboxylase (AADC) – into neurons. Once in the
neurons, cellular machinery kicks into gear to increase production of the AADC
enzyme.
To deliver the treatment, Dr. Richardson will
make a small hole in each side of the patient's skull to insert a thin catheter
into the putamen, a brain region that is an important part of the circuit
affected by Parkinson's disease. After the gene therapy is infused over several
hours, the catheter is withdrawn and the skull is repaired.
Different infusion doses will be tested during
the course of the study. Up to 20 participants at two sites, Pittsburgh and San
Francisco, will be followed for up to three years to have their disease and
medication status reassessed.
The principal investigator of the trial, which
is sponsored by Voyager Therapeutics, is Krystof Bankiewicz, M.D., Ph.D., of
the University of California, San Francisco, who also led an earlier trial that
showed the gene therapy can be safely administered.
More information:
Individuals between 40 and 70 who have had Parkinson's disease for more than
five years and have been taking levo-dopa for at least three years may be
eligible to participate in the trial. For more information, contact Patricia
Porter, B.S., at 412-648-8983 or Porterpm2@upmc.edu.
Provided by: University of Pittsburgh
http://medicalxpress.com/news/2016-02-gene-therapy-parkinson-disease.html?
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