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Potential Parkinson's treatment targets two major nerve systems

Friday January 24th, 2020

A non-invasive gene therapy technique that targets a highly specific group of brain cells has the potential to treat Parkinson’s disease, according to a UK study.

Researchers at the University of Sussex, working with Imperial College London and Invicro, a precision medicine company, have built on work in 2015 that showed that a form of gene therapy could target and stimulate cholinergic neurons, which degenerate as the disease progresses.

Using brain imaging technology, they have discovered their method, which targets cells that produce specific brain chemicals, can also stimulate another type of neuron through cell-to-cell interactions.

Writing in the latest edition of Neurotherapeutics, University of Sussex pharmacology lecturer and senior author Dr Ilse Pienaar say the findings reveal a clear communication pathway between cholinergic neurons and dopaminergic neurons.

People with Parkinson’s have fewer dopaminergic neurons, which produce dopamine, because the neurons deactivate and eventually die, leading to symptoms such as impaired movement.

However, when Dr Pienaar and her colleagues used a type of gene therapy in a rat model of Parkinson's to target cholinergic neurons, they discovered that a therapeutic knock-on effect was also felt by dopaminergic neurons.

Using a harmless virus to deliver a genetic modification to cholinergic neurons in rats rendered Parkinsonian before administering a drug that stimulates target neurons, they found that the originally stimulated cell evoked a positive reaction in the receptive cell type, restoring dopaminergic functions. The rats appeared to make a full recovery, because both groups of nerve cells were stimulated.

Dr Pienaar said: "When we used brain imaging, we found that as we activated cholinergic neurons, they then interacted directly with dopaminergic neurons.

"This seems to be a knock-on effect so by targeting this one set of neurons, we now know that we are able to also stimulate dopaminergic neurons, effectively restarting the production of dopamine and reducing symptoms.

"This is really important as it reveals more about how nerve systems in the brain interact, but also that we can successfully target two major systems which are affected by Parkinson's disease, in a more precise manner."

The researchers hope the technique could eventually be a less invasive and more effective way to treat Parkinson's patients.

Dr Pienaar added: "While this sort of gene therapy still needs to be tested on humans, our work can provide a solid platform for future bioengineering projects."

Sharma PK, Wells L, Rizzo G et al. DREADD Activation of Pedunculopontine Cholinergic Neurons Reverses Motor Deficits and Restores Striatal Dopamine Signaling in Parkinsonian Rats. Neurotherapeutics 21 January 2020

http://dx.doi.org/10.1007/s13311-019-00830-4

Tags: Brain & Neurology | Genetics | UK News

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