Shining the Light V: Humanity is Going to Make It!


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This review will cover the mechanisms of action of photobiomodulation to the brain, and summarize some of the key pre-clinical studies and clinical trials that have been undertaken for diverse brain disorders. Download : Download full-size image. We use cookies to help provide and enhance our service and tailor content and ads.

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Author links open overlay panel Michael R. Under a Creative Commons license. Abstract Photobiomodulation PBM describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. Graphical abstract Download : Download full-size image. But Sklar obviously leans toward optimism. She suggests that the numerous variants provide more chances to home in on key pathways involved in the disorders, and more opportunities to come up with clever ways to fix them.

The hope is that all those genetic variants will tend to affect common sets of molecular pathways, types of cells, or specific neurocircuits. Yet Sklar, who specializes in searching for the genetic causes of schizophrenia and bipolar disorder, acknowledges that despite the rapid advances in genetics over the last few years, large gaps in understanding remain.

Add to this genetic mystery the fact that the brain has roughly 86 billion neurons and around a quadrillion synapses the connecting points between neurons , and it becomes obvious how overwhelming it will be to understand the causes of brain disorders. Now they have a way to directly examine how genetic variants have affected the neurons of a patient with an illness.

You still might not know all the details of the genetics, but at least you can see the results. But how do these neurons function in an actual brain, with its immense networks of circuits and connections? How are the genetic mutations implicated in autism and schizophrenia actually affecting those circuits to alter behavior? New research is starting to investigate those questions. Monkeys and people share a highly developed prefrontal cortex, the region near the front of the skull. Later generations of monkeys could have the multiple mutations found in most forms of autism and schizophrenia.

The monkeys could provide a more reliable way to test psychiatric drugs than rodents, whose brain circuitry is much less similar to ours. It becomes a confirmation that we can correct the circuits and that the changes lead to improvements in behavior. The mouse cowers in one corner of the maze. Even in the video of the experiment, its anxiety seems palpable as it presses against a wall.

Suddenly, after a burst of blue light through the fiber, the mouse begins scurrying about, exploring the four branches of the maze with new energy and courage. The invention of optogenetics has revolutionized the study of neurocircuitry. But even among all the impressive studies using the technology, this mouse experiment, which Kay Tye conducted in as a postdoc at Stanford, stands out. Tye, now an assistant professor at MIT, showed she could turn anxiety on and off with a flip of a switch.

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I was blown away. It has changed how I think about the brain. How can this increasing knowledge of brain circuits and connections—and their role in such feelings as anxiety—be translated into actual therapies? It requires genetic modification of the cells that researchers want to activate and the intrusive use of a fiber-optic thread in the brain. Using the technology to directly fix malfunctioning brain circuits in humans is not now practical, and it may never be.

But as a research technique, it could give drug researchers what they so desperately need: new molecular targets. Researchers like Tye and Feng believe that their optogenetic experiments can help identify specific types of cells in the circuits underlying certain psychiatric symptoms.


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Then they will have to spot distinguishing markers on those cells that allow the drug to recognize them. But the research is still in its very early days. One alternative is to try to intervene directly in the circuits, skipping the use of drugs.

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There might also be ways to directly affect faulty circuits without resorting to surgery. Amit Etkin, an assistant professor of psychiatry at Stanford, is using a combination of functional magnetic resonance imaging fMRI and noninvasive magnetic stimulation to map the circuitry that goes wrong in patients. The therapy, which is administered using an electromagnetic coil placed against the scalp, uses magnetic pulses to create an electric current that can increase or decrease brain activity. The commercial version of the technique is designed to target the same small part of the prefrontal cortex in all patients, but by combining it with imaging technology, Etkin hopes to aim the stimulation more precisely to where a patient needs it.

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The method seems to help only some people. But driving his work, says Etkin, is his frustration at not being able to offer patients more successful options. Etkin, who also works at a clinic at the Palo Alto VA Hospital for veterans suffering from severe anxiety and depression, uses a variety of tools to help patients, including drugs and psychotherapy as well as magnetic stimulation. The key to making all the approaches more effective, he says, is to learn more about how faulty neural circuits and connections lead to aberrant behavior.

And sometimes the gap is significant.

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At Novartis, Ricardo Dolmetsch is responsible for trying to close that gap between the exploding scientific understanding of brain disorders and the availability of more effective drugs. It takes a long time. Dolmetsch is not your typical drug-industry manager. Less than a year ago, he was still running a lab at Stanford and helping to create a library of neurons from autism patients, to be hosted at the Allen Brain Institute in Seattle. About a decade ago, his research took a dramatic turn. He had started out at Stanford looking into basic questions about the biochemistry in brain cells, work that was impressive enough to gain him an appointment as an assistant professor.

But then, in , his son received a diagnosis of autism. Frustrated by the lack of treatment options, Dolmetsch rebuilt his lab around researching the disorder. Since then, he has helped pioneer methods that take skin cells from individuals with autism, reprogram those cells to become stem cells, and then induce them to develop into neurons in which abnormalities can be studied.

Designing drugs to precisely target circuits in the brain remains a more distant opportunity. But that still leaves the daunting challenge of developing a drug that selectively activates or inactivates certain types of cells in certain circuits. Dolmetsch joined the pharmaceutical industry because he realized that the science and technology had advanced far enough to create opportunities for developing new psychiatric drugs. He also realized after years of academic research that commercializing a new drug requires the resources, money, and patient populations available to a company like Novartis.

Still, the failure to find effective new drugs for brain disorders—and the stigma that has grown around the high cost of those failures—is clearly never far from the minds of those in the industry.


  1. Shining the Light Series | Light Technology Publishing.
  2. Works of John Lancaster Spalding!
  3. Her Silent Hell.
  4. But at least now, after decades of dead ends, drug researchers finally have some of the tools they need to begin methodically testing strategies for finding and acting on those targets. David Rotman.

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    Shining the Light V: Humanity is Going to Make It! Shining the Light V: Humanity is Going to Make It!
    Shining the Light V: Humanity is Going to Make It! Shining the Light V: Humanity is Going to Make It!
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