How Modeling the Brain’s Electrical Network Could Develop Therapies for Huntington’s Disease

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Understanding how Huntington’s disease disrupts the brain’s wiring could give medical researchers insights needed to find a way to slow or even stop the progression of this deadly disorder. Read about how brain-simulator software developed by IBM scientists offers that promise.

Huntington’s disease, a fatal genetic disorder that causes a progressive breakdown of the brain’s neurons, afflicts about five to seven people per 100,000 in western countries, and is famous for taking the life of folksinger Woody Guthrie. But despite millions of dollars spent over the past two decades to investigate the disease, there’s been little progress in developing a drug or therapy to stop its ravages.

That’s why IBM neuroscientist and inventor James Kozloski thinks it’s time for a new approach. By using a supercomputer and sophisticated neural simulation software to look at Huntington’s from a new angle — its effect on the brain’s electrical signaling networks — Kozloski and his colleagues at the Thomas J. Watson Research Center in Yorktown Heights, New York, hope to finally achieve a lifesaving breakthrough.

“Huntington’s is caused by a single mutant protein,” explains Kozloski. “But what that protein actually does is a mystery. That’s what we’re trying to find out.”

Simulating the Brain’s Wiring

Instead of focusing on genetics or biological processes, the IBM researchers are trying a new approach that lies at the intersection of medicine and information technology. They’re using a piece of software called the Neural Tissue Simulator, which runs on the IBM Blue Gene supercomputer, to investigate Huntington’s effect on the brain’s electrical signaling system at its most basic level — how individual neurons “talk” and “listen” to one another.

That communication, Kozloski explains, enables the brain to form sprawling networks of connected neurons to carry out its various functions. The IBM researchers’ theory is that Huntington’s mutant protein subtly changes the way that neurons receive those signals, which causes them essentially to get the message wrong and then send an errant response that gradually cascades though the rest of its network — sort of the way that a mistaken idea can go viral on the Internet.

“It could be that the Huntington’s gene is causing the neuron to relate to its neighbors in a way that’s slightly different from how it’s supposed to,” Kozloski explains. “If that’s so, the circuit might be adjusting to a whole different set of conditions.”

But to understand how the disease does its damage, researchers need to be able to peruse both the interactions among neurons and the effects across larger neural networks in the brain. Fortunately, IBM’s brain-simulating software is well equipped to do just that. As Kozloski explains, the software can zoom in and look at how a tiny sliver of a simulated brain works electrically, and then zoom out to see network activity.

Using Brain Simulation to Guide the Search for a Huntington’s Cure

The IBM research effort eventually could help us to understand exactly how Huntington’s damages the brain and eventually kills a person. But it also could help speed up development of a treatment for slowing or stopping the disease, because researchers can model the effects of a new drug or a therapy such as electrical deep-brain stimulation, looking at the effect from the cellular level right up to the network, according to Kozloski. The computer modeling might give doctors ideas on how to adjust dosages, for example, that might not occur to them otherwise — and spark human trials.

“We’re not going to replace clinical trials, but we could provide justification for new levels of clinical research,” Kozloski says. His hope is that such an insight may lead to a treatment to stop Huntington’s that for too long has eluded medicine.

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Source: people 4 smarter cities

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