By Andrew Deck
A new wave of medical technologies is changing the way we approach studying the brain and treating patients suffering from neurological diseases and mental illness.
For people suffering from Parkinson’s, epilepsy, OCD and severe depression, these technological advancements are parting the sea of neuropharmacology by offering targeted, noninvasive alternatives to pills.
“Drugs flatten your whole body,” said Thomas Knöpfel, chair of optogenetics and circuit neuroscience at Imperial College of London. “You want to treat an organ, like the brain, but you also end up with receptors on your kidneys and liver, and a lot of side effects.”
Instead of ingesting pills that have a far-reaching impact, what if you could go directly to the source of brain diseases by activating brain cells? Doctors are testing this idea with treatments such as deep brain stimulation (DBS) and optogenetics, which combines light and genetics to control events within cells of living tissue.
DBS is not new. In fact, the first procedure was conducted by a French neurosurgeon in 1987. But it was only in the last decade that DBS technology was refined and widely accepted as a treatment for Parkinson’s disease and movement disorders, according to Dr. Mark Richardson, assistant professor of neurological surgery at the University of Pittsburgh.
While DBS is not a cure, it can improve the quality of life for a patient by lessening or eliminating the symptoms of movement disorders such as tremors and stiffness, he said.
The procedure involves inserting two 3-millimeter-long electrodes beneath the brain’s surface. Wires run down the brain and neck to connect with a battery pack, about the size of a stopwatch, under the skin of a patient’s chest.
Nicknamed the brain “pacemaker,” descriptions of DPS electrodes as “shocking” the brain are hyperbolic, Richardson said.
Rather, they emit a low, continuous electrical current that disrupts any abnormal electrical activity in the diseased brain. This abnormal activity causes tremors, stiffness and other symptoms of movement disorders.
During checkups, doctors will use a wireless remote to increase or decrease the rate of the charge, optimizing its effects. It may take up to six months to program the device and fully realize its benefits.
Richardson attributes this trial-and-error period to the persistent unknowns of DBS research.
“There is still plenty of science in the field that remains to be uncovered,” he said. “But it is important to note that it does work really well, even if we don’t fully know why it works really well.”
One other unknown, is the part DBS will play in treating mental illness.
The Food and Drug Administration (FDA) approved DBS for essential tremors in 1997 and Parkinson’s in 2002, but severe depression and post-traumatic stress disorder (PTSD) treatments are still awaiting federal approval. Severe obsessive compulsive disorder (OCD) is the only mental illness that has received an FDA sanction.
That being said, many advanced trials are underway that provide DBS treatment for mental illnesses. Patients with severe depression in trials have experienced positive mood changes and the elimination of suicidal thoughts.
“We’re still not sure which patients are going to benefit from DBS who have depression or OCD,” Richardson said. “I think DBS will become an established therapy for mental illness, but right now we don’t know enough.”
Despite the promise of DBS, some feel it falls short of being a truly targeted treatment.
“The brain is composed of more cells than people living on Earth,” Knöpfel said. There are approximately 86 billion neurons in the brain, according to recent estimates.
While DBS stimulates a general region of the brain, Knöpfel said a more effective treatment would stimulate the individual neurons responsible for a brain disorder.
Optogenetics may be that solution, he said.
Optogenetics has made waves in the neuroscience community in the last five years, ever since Nature named it “2010 Method of the Year.” With optogenetics, a neuron or a type of neuron is genetically engineered to be light-sensitive. Therefore, when you expose those neurons to a light source they will immediately activate. When brain tissue is under a microscope, a researcher could see exactly how dopamine affects the brain. This could lead to major breakthroughs in Parkinson’s, schizophrenia and addiction research, Moore said.
Instead of activating an entire region of the brain, as DBS does, optogenetics can activate just the abnormal cells responsible for a brain disease, leaving the healthy cells undisturbed.
But there are roadblocks to clinical applications. Unlike DBS, which has decades of clinical history and is FDA approved for multiple conditions, optogenetics currently has only one human trial.
Optogenetics-based treatments for movement disorders and mental illness are theoretical, while DBS treatments are proven. Two major engineering hurdles stand in the way of further optogenetics trails. The first is human genetic engineering.
“I think optogenetics is a powerful technique, but people do not fully understand that currently gene therapy in the human brain is very experimental,” DBS-specialist Richardson said. “You need to be able to get the right gene to the right type of cell in the right brain region. I think it is underdiscussed, because how you do that is incredibly complicated.”
Light delivery also presents a challenge for researchers.
“You just don’t see light beams coming through someone’s skull,” said Moore, explaining why it is difficult to introduce light into the human brain.
While fiber optics cables inserted into the brain have been employed as a light source, Moore asks whether, at its current level of effectiveness, this invasive approach is warranted.
Both DBS and optogenetics are far from perfect technologies, but they are notable because their method of brain activation presents an alternative to drug-centric treatment plans.
A study conducted by the National Institute of Neurological Disorders and Stroke (NINDS) and the Department of Veterans Affairs compared DBS treatment with the “best medical therapy” for Parkinson’s, which included medication and physical therapy. Their finding: “DBS showed overall superiority to the best medical therapy at improving motor symptoms and quality of life.”
While Richardson says medical management will fall to the wayside due to these advancements, he does believe they will continue to improve and gain credibility in the clinical community as an established form of treatment.
“I think pharmacological treatment has its place, but once the medications are not working we need other solutions,” he said.
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