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This is great news! Kathleen 2009/8/28 [log in to unmask] <[log in to unmask]> > This was one of the last missing parts to the puzzle - how to turn off gene > therapy, if needed, > Subject: off switch for gene therapy > Date: Sat, 29 Aug 2009 01:02:12 GMT > Public release date: 28-Aug-2009 > From EurekaAlert > > Contact: John Pastor > [log in to unmask] > 352-273-5815 > University of Florida > > UF scientists construct 'off switch' for Parkinson therapyCommon drug shuts > down gene therapy in rats, addressing safety concerns for humansGAINESVILLE > — A common antibiotic can function as an "off switch" for a gene therapy > being developed for Parkinson's disease, according to University of Florida > researchers writing online in advance of September's Molecular Therapy. > > The discovery in rats answers an important question — how can new, > therapeutic genes that have been irrevocably delivered to the human brain to > treat Parkinson's be controlled if the genes unexpectedly start causing > problems? > Meanwhile, in a review of Parkinson treatments, the researchers say that > prior experimental attempts using growth factors — naturally occurring > substances that cause cells to grow and divide — to rescue dying brain cells > may have failed because they occurred too late in the course of the disease. > > Together, the findings suggest that gene therapy to enable the brain to > retain its ability to produce dopamine, a neurotransmitter that falls in > critically short supply in Parkinson's patients, could be safely attempted > during earlier stages of the disease with an added likelihood of success. > > Parkinson's disease affects more than 1 million Americans, causing patients > to gradually develop movement problems, including tremors, stiffness and > slowness. It is caused by degeneration and death of nerve connections that > produce dopamine, a substance necessary for communication between cells that > coordinate movement. > "We have worked every day for 10 years to design a construct to the gene > delivery vector that enhances the safety profile of gene transfer for > Parkinson's disease," said Ronald Mandel, a professor of neuroscience at > UF's McKnight Brain Institute and the Powell Gene Therapy Center. "With that > added measure of safety, we believe we can intervene with gene transfer in > patients at earlier stages of the disease. We strongly believe that trials > to save dopamine-producing connections in patients with Parkinson's disease > have failed because the therapy went into patients who were in the late > stages of the disease and who had too few remaining dopamine-producing > connections." > > Often patients are given prescriptions for levodopa, or L-dopa, which is > converted into dopamine by enzymes in the brain. But the treatment loses its > effectiveness over time and does nothing to slow the disease's progression. > Meanwhile, trials in the United States to treat Parkinson's involving > direct infusion of growth factors or the transplantation of genes that > produce growth factors have had limited success, with some side effects. > Mandel's research group has concentrated on using an adeno-associated virus > to engineer brain cells in animal models with genes that can protect > dopamine-producing cells, which then do the vital work of producing GDNF, > short for glial cell line-derived neurotrophic factor. The naturally > occurring protein is important for the survival of dopamine-producing > neurons during brain development, and a survival factor when given to > adults. > In this case, scientists engineered the virus with two genes that must act > in concert to produce the protein. But this precise interaction can be > inhibited with dietary doxycycline, an antibiotic that is often prescribed > in low doses to treat bacterial growth related to acne. > > Depending on the amount of the antibiotic, protein production can be > reduced or stopped, which would for the first time give medical > investigators the ability to regulate gene therapy after the treatment was > delivered. > "With this technique, you could adjust the therapy in the patient," said > Fredric P. Manfredsson, a postdoctoral associate in UF's department of > neuroscience. "That would be extremely helpful because no one is really > certain yet what dosage is required for a protective effect in humans. The > process is also much more sensitive than we had imagined it would be. GDNF > production can be shut down completely with a dose of doxycycline that is > much smaller than what is commonly prescribed." > Mandel said that adding the safety construct to the gene vector and proving > its effectiveness were arduous tasks in which Manfredsson played an > essential role. > > A variety of methods were used to gauge GDNF production, but one was > uncommon and involved the novel observation of the rats' weight. In prior > research, the scientists had found delivering the protein to certain regions > of the brain would hinder weight gain in younger rats and can cause weight > loss in older rats. In the recent experiments, scientists found they could > control the rate of weight gain in the rats with dietary doxycycline, which > essentially verified they were controlling the GDNF therapy. > "The ability to control gene regulation is important for the future > development of gene therapy, and optimizing its safe application to humans," > said Dr. Mark Tuszynski, a professor of neurosciences and director of the > Center for Neural Repair at the University of California, San Diego, who did > not participate in the research. "The work of Dr. Mandel and colleagues > brings us an important step closer to this goal." > > http://www.eurekalert.org/pub_releases/2009-08/uof-usc082809.php > > > __._,_.___ > > > __,_._,___ > > ---------------------------------------------------------------------- > To sign-off Parkinsn send a message to: mailto: > [log in to unmask] > In the body of the message put: signoff parkinsn > ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn