(may be a foolish question--though given the results of this study in an animal model, utilizing doxycycline (a tetracycline class drug) to functionally decrease production of GDNF, would this apply to humans? Should individuals with PD not take doxycycline? Or does this effect not matter clinically?I do not have the original study, so do not know what the "side effects" from GDNF are defined as. I do recall (couple yrs ago?) study utilizing minocycline (tetracycline class of drugs, as is doxycycline)in neurodegenerative diseases for its interference with microglia activation... I remember minocycline crosses the BBB. Confusing. )

MrsD, any insight, or am I over-reading/mis- associating this stuff again?


http://blog.taragana.com/health/2009...therapy-10952/
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(GDNF) 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 (GDNF).

But this precise interaction can be inhibited with dietary doxycycline, an antibiotic..

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...

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...

(Abstract of study to which the above report refers: [had I first read this abstract, I would NEVER have known the study involved using doxycycline to decrease the production of GDNF}


http://www.nature.com/mt/journal/v17...t2009196a.html
Molecular Therapy 17, 1857–1867 (1 November 2009) | doi:10.1038/mt.2009.196



Tight Long-term Dynamic Doxycycline Responsive Nigrostriatal GDNF Using a Single rAAV Vector
Fredric P Manfredsson , Corinna Burger , Aaron C Rising , Kheir Zuobi-Hasona , Layla F Sullivan , Alfred S Lewin , Julia Huang , Emily Piercefield , Nicholas Muzyczka & Ronald J Mandel

Glial cell line-derived neurotrophic factor (GDNF) gene transfer is being developed as a treatment for Parkinson's disease (PD). Due to the potential for side effects, external transgene regulation should enhance this strategy's safety profile. Here, we demonstrate dynamic control during long-term expression of GDNF using a recombinant adeno-associated virus (rAAV)-based bicistronic tetracycline (tet)-off construct... Molecular Therapy (2009) 17 11, 1857–1867. doi:10.1038/mt.2009.196