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Gene therapy eases Parkinson's by rewiring brain

3 December 2018
Appeared in BioNews 978

A gene therapy relieves Parkinson's disease symptoms by rewiring the brain circuits involved in movement.

The trial was first published in 2011; patients were given injections of a gene encoding the enzyme glutamic acid decarboxylase (GAD) into the subthalamic nuclei (STN) of their brains. Those patients who received the therapy had improved movement which was sustained for up to one year after treatment. However, the method of action behind this improvement was unknown.

Now, researchers at the Feinstein Institute for Medical Research in Manhasset, New York, believe the positive effects to be mediated by the formation of new brain circuitry.

'Shutting down the disease-causing pathways between the STN and the brain's motor regions appeared to encourage alternative pathways to develop instead,' said Dr David Eidelberg, senior author on the study.

The paper, published in Science Translational Medicine, analysed PET scans taken from 15 patients who received the gene therapy, and 20 sham-treated placebo controls. The new brain circuitry found in patients is not found in healthy individuals, suggesting that 'gene therapy lets people with Parkinson's form novel, compensatory brain circuits for controlling movement' a term called 'adaptive rewiring' said Dr Eidelberg.

One of the most debilitating symptoms of Parkinson's disease is a constant tremor, caused by overstimulation of the STN. Therefore, as the therapy appears to dampen the activity of the STN, it is beneficial to patients.

While the therapy may be promising, Professor Hideki Mochizuki at Osaka University, Japan, who was not involved in the study, told AlzForum that the 'clinical outcome [of the therapy] should be compared with deep brain stimulation in terms of safety and efficacy before wide-range application could be envisaged'.

According to AlzForum, a British gene therapy company has now purchased the rights to the treatment. A phase three clinical trial of the therapy is planned to start in late 2019.

SOURCES & REFERENCES
Gene therapy eases Parkinson’s symptoms by rewiring parts of the brain
New Scientist |  28 November 2018
Gene therapy reduces Parkinson’s disease symptoms by reorganizing functional brain connectivity
Science Translational Medicine |  28 November 2018
Imaging Data Resurrects Abandoned Parkinson's Gene Therapy
AlzForum |  30 December 2018
Parkinson’s therapy creates new brain circuits for motor function, study finds
Feinstein Institute for Medical Research |  28 November 2018
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