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Common drug can function as 'off switch' for Parkinson therapy.

Byline: ANI

Washington, Aug 29 (ANI): A common antibiotic can act as an "off switch" for a gene therapy that is being developed for Parkinson's disease Parkinson's disease or Parkinsonism, degenerative brain disorder first described by the English surgeon James Parkinson in 1817. When there is no known cause, the disease usually appears after age 40 and is referred to as Parkinson's disease. , according to a study on rats conducted by University of Florida University of Florida is the third-largest university in the United States, with 50,912 students (as of Fall 2006) and has the eighth-largest budget (nearly $1.9 billion per year). UF is home to 16 colleges and more than 150 research centers and institutes.  researchers.

The findings of the study have explained how new, therapeutic genes that have been irrevocably delivered to the human brain to treat Parkinson's can be controlled if the genes unexpectedly start causing problems.

Meanwhile, in a review of Parkinson treatments, the researchers have said that earlier experiments 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.

Taken together, the findings have indicated 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.

"We have worked every day for 10 years to design a construct to the gene delivery vector Noun 1. gene delivery vector - a vector for delivering genes into cells
transducing vector

liposomal delivery vector - a transducing vector that uses liposomes to carry the gene of interest
 that enhances the safety profile of gene transfer for Parkinson's disease," said Ronald Mandel, a professor of neuroscience at UF.

He added: "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 levodopa: see l-dopa.
levodopa
 or L-dopa

Organic compound (L-3,4-dihydroxyphenylalanine) from which the body makes dopamine, a neurotransmitter deficient in persons with parkinsonism.
 (L-dopa), which is converted into dopamine dopamine (dōp`əmēn), one of the intermediate substances in the biosynthesis of epinephrine and norepinephrine. See catecholamine.
dopamine

One of the catecholamines, widely distributed in the central nervous system.
 by enzymes in the brain. But such treatment is not effective over time, and does nothing to slow the disease's progression.

In the meantime Adv. 1. in the meantime - during the intervening time; "meanwhile I will not think about the problem"; "meantime he was attentive to his other interests"; "in the meantime the police were notified"
meantime, meanwhile
, trials in the US 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 Side effects

Effects of a proposed project on other parts of the firm.
.

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 glial cell line-derived neurotrophic factor Glial cell line-Derived Neurotrophic Factor (GDNF) is a small protein that potently promotes the survival of many types of neurons. Functions
The most prominent feature of GDNF is its ability to support the survival of dopaminergic and motorneurons.
 (GDNF GDNF Glial-cell Line-Derived, Neurotrophic Factor
GDNF Gesinnungsgemeinschaft der Neue Front (German) 
).

The naturally occurring protein is important for the survival of dopamine-producing neurons during brain development, and a survival factor when given to adults.

For the current study, the researchers 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 doxycycline /doxy·cy·cline/ (dok?se-si´klen) a semisynthetic broad-spectrum tetracycline antibiotic, active against a wide range of gram-positive and gram-negative organisms; used also as d. calcium and d. hyclate. , 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. 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," said Fredric P. Manfredsson, a postdoctoral associate in UF's department of neuroscience.

The researchers used a number of methods to gauge GDNF production, but one was uncommon and involved the novel observation of the rats' weight.

The scientists found that they could control the rate of weight gain in the rats with dietary doxycycline, which essentially verified they were controlling the GDNF therapy.

The study has been published in the journal Molecular Therapy. (ANI)

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Publication:Asian News International
Date:Aug 29, 2009
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