hi all

i wouldn't mind having restored consistent function
in both of my front paws!

janet
but i'd have to be bribed with a lot of cheese
before undergoing brain surgery!
this mouse is a chicken

---------------------------------------------------
Rats With Partial Parkinson’s Damage In The Brain Show Complete Functional
Recovery After Gene Therapy

Date Posted:    Monday, April 01, 2002 - GAINESVILLE, Fla. - Scientists
report this week they have demonstrated that the injection of two
corrective genes into a specific brain region generated significant
restoration of normal limb movement in rats with a chemical-induced form of
Parkinson’s disease.

The findings – by a team of researchers from the University of Florida in
Gainesville and Lund University in Lund, Sweden – are published in the
current online version of the journal of the Proceedings of the National
Academy of Sciences.

Neuroscientists Anders Bjorklund of Sweden and Ronald Mandel with UF said
the strategy that proved effective in the rodents is not a cure for
Parkinson’s disease, but is expected to lead to a better method for
delaying and controlling symptoms of the progressively disabling condition.

About 1 million Americans are affected by Parkinson’s disease, which occurs
most often between the ages of 65 and 90.

"We found that the simultaneous delivery of two selected genes, coupled
with a powerful gene-activating agent, works like a pump to prime the
production of L-dopa, which is then converted into dopamine by appropriate
nerve cells in the brain," said Mandel, a professor of neuroscience with
UF’s Evelyn F. and William L. McKnight Brain Institute and the UF Genetics
Institute. Dopamine is a neurotransmitter chemical that plays a lead role
in coordinating limb movements.

Limb impairments were completely reversed in rats that had near-total
Parkinsonian lesions on only one side of the brain, meaning that some of
their dopamine-producing cells remained intact.

These partial lesions mimic the kind of damage (progressive death of
L-dopa-producing cells) found in people with the disease, according to the
scientists.

Even in the rats with complete destruction of dopamine-producing cells, the
delivery of gene therapy resulted in a limited amount of restored motor
function.

"Quite frankly, I was surprised by this successful outcome, since our
previous experiments in the same animal model failed to result in restored
motor function," said Mandel.

One key to success, he said, was to figure out how much L-dopa the
corrective genes need to generate to produce long-lasting functional
effects. "Our team was first to determine this critical threshold," he said.

The experiment that helped the rats regain motor function involved a single
injection of two different genes, each packaged separately along with the
selected gene promoter in a gene-transport molecule (vector). Both genes
code for enzymes essential to triggering production of L-dopa.

Based on prior discoveries by Dr. Bjorklund, the researchers injected these
genes into the striatal region of the forebrain, the destination point of
dopamine-producing cells.

When the injected vectors land in this area, they deposit their payload of
genes, which are "turned on" by the gene-promoter (a selected segment of
DNA) to initiate L-dopa production.

Mandel said videotapes of the rats moving about in tall clear-glass
cylinders provide the most visible demonstration of the spontaneous
behavior regained after gene therapy.

Initial tapes show healthy rats standing up and exploring the sides of the
cylinder with their front paws while walking around on their hind legs.

In the next tapes, taken after the induction of Parkinsonian lesions, the
rats can be seen dragging one limp and rigid front paw while walking around
and exploring their environment with the normal front limb.

Then, in videos taken after gene therapy, the same rats demonstrate normal
function of both front paws.

The vector used for the studies was the apparently harmless
adeno-associated virus, or AAV, developed at UF as a gene carrier in the
early 1980s by Nicholas Muzyczka, an eminent scholar with the UF Genetics
Institute and a co-researcher in the Parkinson’s study, and Dr. Kenneth
Berns, molecular biologist. UF holds the patent on use of the AAV vector in
the brain.

Mandel said the effectiveness of gene therapy in the Parkinsonian rats
generates hope that the therapy can eventually be applied in humans, with
the potential to double the time a person with Parkinson’s disease will
respond well to standard medications.

Typically a patient responds well to medication for three to five years,
but the beneficial effects gradually diminish because side effects begin to
reduce the therapeutic value of the drug.

"Before the U.S. Food and Drug Administration may approve this type of
therapy for human testing, we have to solve a critically important
problem," said Muzyczka, who also is co-director of the Powell Gene Therapy
Center at UF.

"The gene promoter we’re now using stays turned on continually, resulting
in continuous dopamine production unlike the way our bodies adjust this
production to meet our needs.

"We need a gene regulator that functions more like a rheostat to turn
dopamine production on and off as needed to sustain normal limb movement."

UF researchers now are investigating several promising candidate gene
promoters. Muzyczka said he is optimistic that human application may occur
in about five years.

"We anticipate gene therapy will offer a way to help patients with
Parkinson’s disease live many years longer free of disabling symptoms,"
Mandel said.

"There is no reason why gene therapy couldn’t also be given in addition to
medication and surgical procedures such as pallidotomy, or deep-brain
stimulation."

The research reported in the journal results from more than four years of
studies involving nearly 200 rats.

Funding came from the Swedish Medical Research Council, and the Knut and
Alice Wallenberg Foundation.

Source:             University Of Florida
Copyright © 1995-2002 ScienceDaily Magazine | Email: [log in to unmask]
Web Address:   http://www.sciencedaily.com/releases/2002/04/020401075214.htm


janet paterson: an akinetic rigid subtype, albeit perky, parky
pd: 55/41/37 cd: 55/44/43 tel: 613 256 8340 email: [log in to unmask]
smail: 375 Country Street, Almonte, Ontario, Canada, K0A 1A0
a new voice: http://www.geocities.com/janet313/

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