Crowd-sourcing optogenetics data to tackle neurological diseases

Published on: 21 October 2020

Around the world, some 50 million people have epilepsy. It’s one of the most common neurological diseases globally, characterised by recurrent seizures in part or all of the body.

Epilepsy is treatable with daily antiseizure medications, yet like many prescription drugs these have side effects, and they can’t target the exact spot in the brain triggering the seizures.

Researchers at Newcastle University and the University of Pennsylvania see potential in another option called optogenetics. This field uses genetic techniques to increase the light sensitivity of specific neurons in the brain and controls their activity with direct light. 

Professor Chris Petkov, from Newcastle University’s Faculty of Medical Sciences, said: “In the future, optogenetics could help treat neurological diseases with high precision and accuracy, so it’s an exciting step forward in research.”

Central database

Despite a large neuroscience community working on optogenetics, scientists noticed that no central database existed to foster information exchange, particularly related to the subset of optogenetics focused on nonhuman primates.

That meant anything not published in an academic journal – which, in this case, represented nearly half of in-progress work – never saw the light of day.  And without knowing what had previously succeeded or failed, optogenetics researchers were constantly reinventing the wheel.

“We realised there was research out there in this field that hadn’t been published, where people had tried different techniques, different viral vectors, and just never reported it,” says Michael Platt, a Penn Integrates Knowledge Professor.

“For all the work that had been published, none of it had been collected into a single database.”

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A paper, just published in the journal Neuron, details the results of an open-source database that includes raw data and results from 45 labs in nine countries working on optogenetics in nonhuman primates. The paper also describes preliminary results of a meta-analysis conducted about what has and has not worked so far.

Optogenetics is relatively new and was developed approximately 15 years ago. To date, many of its achievements have come by way of small animal models. For optogenetics to become a safe and efficient clinical tool for humans, however, the science must first succeed in an intermediate step with nonhuman primates.

Professor Petkov said: “This database is an important global initiative that combines the expertise of scientists around the world, to which we were delighted to contribute.

“Newcastle University is actively assessing optogenetics for treatment of debilitating neurological diseases. Animal research remains indispensable in this regard for developments that in the future can translate to next generation treatments.”

To ensure the quality of the resource they were building, the University of Pennsylvania researchers added crucial context to each entry, including the type of virus used to deliver the genetic materials what’s known as the viral vector—plus experimental methodology and results related to anatomy, physiology, and behaviour, among other factors.

Data analysis

From the data analysed, several evidence-based conclusions have been made about the progression of nonhuman primate optogenetics in the past decade and a half.

For one, many experiments successfully modulate activity in the brain but do not alter behaviour – they change what the neurons are doing but not the actions that flow from that.

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“This is critical because if we want this to have clinical value for patients it needs to do more than play with neurons,” says Dr Sébastien Tremblay, a Research Associate from the University of Pennsylvania.

“It needs to reduce the symptoms of Parkinson’s or Alzheimer’s or any other disease. This is a gap we have to fill.”

Beyond that, researchers found there’s far more optogenetics can learn from gene therapy, particularly in terms of the best mechanisms to express proteins in the brain. The scientists were also able to rank many of the parameters, determining, for example, what caused the most light sensitivity or which viral vectors worked most efficiently.

All of this is with an eye toward human clinical trials. “What’s special about these techniques is that we can stimulate the exact part of the brain and even a subset of the neurons within that part of the brain,” Dr Tremblay says.

“It’s unlike using a drug, which will go to the brain but will also hit other organs and create collateral damage. It’s also a new level of precision that never existed before.”

For someone with epilepsy, for instance, such a technique could selectively turn off seizures by targeting the exact spot in the brain that’s triggering them.

Press release adapted with thanks to the University of Pennsylvania 


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