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Common Antibiotic Can Act As An ‘Off Switch’ For Parkinson’s Therapy
In the meantime, 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.
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 (GDNF).
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, 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.
Source-ANI
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