Kristin “Sunny” Berry lived with essential tremor for more than 50 years. The neurological disorder caused her hands and jaw to shake uncontrollably, which only worsened with age. Medication seemed to do little for the 59-year-old apartment property manager.Simple tasks like dressing and eating became “impossible”; she often damaged her gums when she brushed her teeth. She abandoned many of her creative passions; the excruciating effort of steadying a pen or paintbrush left her in tears.
Then, last April, Berry enrolled in a clinical trial at Ohio State Universityto quell the tremor in her right hand with focused ultrasound, a procedure that uses beams of sound energy to destroy abnormal neurons in the brain, no surgery needed. Berry went back home to Howell, Michigan, the next day with no side effects other than some unsteadiness and mild numbness in her scalp. Now, the tremor in her right hand is 85 percent gone, she says — and she’s resumed painting. “It’s like being born again,” she says.
In an earlier study with mice, Lipsman and his colleagues found that focused ultrasound alone can help clear brain plaques suspected to contribute to Alzheimer’s disease.
The FDA approved focused ultrasound for essential tremor last July, but researchers are investigating its potential as a noninvasive, highly targeted therapy for a broad range of devastating neurological and psychiatric disorders, including Parkinson’s and Alzheimer’s disease, depression and obsessive-compulsive disorder (OCD). Ultrasound also could disrupt the nearly impenetrable blood-brain barrier, allowing the delivery of drugs and gene therapy. The need is urgent; the World Health Organization estimated that one billion people worldwide suffer from neurological disorders, yet few effective treatments exist.
More established technologies like deep-brain stimulation deliver electric current to treat psychiatric and movement disorders, but they either don’t reach the deeper structures involved in many brain disorders or, in the case of deep-brain stimulation, require surgically implanting electrodes. Focused ultrasound can address both limitations. Patients wear a helmet-like device and lie in an MRI scanner that relays real-time images of the brain to clinicians. Much like a magnifying glass focuses sunlight to singe a leaf, a “lens” concentrates ultrasound beams to destroy abnormally functioning neurons deep inside the brain, explains Neal Kassell, founder and chairman of the Focused Ultrasound Foundation. (Typically, the ultrasound is emitted at a frequency the human ear can’t detect.)
Researchers are harnessing these sonic beams to treat some of the most perplexing brain disorders. Nir Lipsman of the Sunnybrook Health Sciences Centre in Toronto is about to launch clinical trials of focused ultrasound in people with depression and OCD, which could offer relief to the one-third of people with mood and anxiety disorders who don’t respond to drugs or therapy. Both trials will involve the same procedure but different targets. Lipsman expects to receive approval to conduct the OCD trial in the next few weeks and the depression study sometime this year.
Others are using lower-intensity focused ultrasound to jolt neural circuits rather than destroy abnormal neurons. A 25-year-old coma patient at Ronald Reagan UCLA Medical Center in Los Angeles regained consciousness and language comprehension just three days after researchers stimulated neurons in the thalamus (a key gateway for consciousness and complex thought processes) with a device that emits focused ultrasound at a low intensity. Assuming it consistently helps others recovering from comas, Martin Monti, a professor of psychology and neurosurgery at UCLA, envisions a device that delivers the signal built into “a little helmet.” Jean-Paul Aubry, director of France’s National Center for Scientific Research, imagines a similar device for psychiatric and movement disorders.
Sreekanth Chalasani of the Salk Institute for Biological Studies in La Jolla, California, is investigating the use of ultrasound to switch specific neurons on and off. His lab has genetically engineered the neurons in nematodes (a type of worm) to contain channels that open in response to ultrasound, a technique known as sonogenetics. Ultrasound activates these neurons, causing the critters to alter their behavior, such as change direction. Sonogenetics might offer a noninvasive way to turn off neurons involved in disease — that is, once scientists figure out how to insert ultrasound-sensitive channels into human neurons. For now, Chalasani’s lab is trying to get sonogenetics to work in mice.
Scientists also are using ultrasound to breach the blood-brain barrier, a layer of densely packed cells that prevents viruses and other harmful substances from entering the brain — and drugs for brain disorders from reaching their targets. The procedure involves injecting the patient with microscopic bubbles. Focused ultrasound makes the bubbles vibrate and nudge apart the cells in the barrier. So far, the technique has enhanced the delivery of therapeutic agents to brain tumors in rodents and improved their response to treatment. But in an earlier study with mice, Lipsman and his colleagues found that focused ultrasound alone may help clear brain plaques suspected to contribute to Alzheimer’s disease. Following up on these findings, they recently began recruiting subjects for a trial to test the strategy in Alzheimer’s patients.
To be sure, “focused ultrasound is still in its infancy,” Monti says. Even if focused ultrasound receives FDA approval for treating brain disorders in addition to essential tremor, “it’s not a panacea,” Lipsman says. He doesn’t foresee it replacing existing technology, like deep-brain stimulation and other techniques that deliver electric current to the brain, but instead offering more options to personalize treatments.
As a patient, Berry is enthusiastic about what lies ahead. She initially considered surgical removal of the neurons responsible for her tremor, but it sounded dangerous, and she worried about the risk of infection. “The mere fact that [focused ultrasound] is noninvasive is massive,” she says. “I’m highly optimistic.” She plans to undergo focused ultrasound for the tremor in her left hand in a few years.
