Advances in Treatments for Movement Disorders

Jeffrey S. Schweitzer, MD, PhD, and Ziv Williams, MD, neurosurgeons at Mass General, are actively researching possible treatments for Parkinson’s, epilepsy and other movement disorders. Dr. Schweitzer and Dr. Williams are studying the use of a patient’s own cells as a source of replacement neurons. Dr. Schweitzer explains that Parkinson’s disease is being used as the initial target for cell-based therapy because the motor impairments are largely caused by the loss of a single, well-understood type of brain cell. 

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“The hope has always been that rather than offer symptomatic treatment, such as deep-brain stimulation, we could develop a cure,” Dr. Schweitzer says. “There are many labs around the world that are working on this, and there have been very encouraging results in animal models.”

Adult Cells as the Basis of Therapy

Previous sources of the stem cells presented ethical, practical and clinical problems. But now, Dr. Schweitzer says, innovative technology allows for the use of induced pluripotent stem cells from adults, cells which can then be used to create in the laboratory specific cell types suitable for implantation.

“We take a skin biopsy, and four specific chemical signals can be put into cells from that sample to turn them back into undifferentiated stem cells,” he explains. “Once you’ve got a cell back to its embryological condition, you can give it step-by-step instructions that fool the cell into thinking it’s in a particular site or part of an embryo,” notes Dr. Schweitzer. “Branch by branch along the tree, you persuade it to differentiate into the type of tissue you want.” In this case, that’s a midbrain dopamine neuron.

Dr. Schweitzer has partnered with a research team from Harvard Medical School that has developed a safe method of maturing the cells to the desired type—the kind of brain cells lost in Parkinson’s disease—and treating the cells in a special way such that no cancer cells result

Trials of Cell-based Therapies on the Horizon

Presently, no government in the world has approved a cell-based therapy for Parkinson’s disease. However, over the last three years Dr. Schweitzer and his colleagues have actively pursued a pilot study toward this goal, and Dr. Schweitzer’s team is working with the FDA to gain approval for a formal clinical trial that they hope to begin in 2019.

“We’re right there on the cutting-edge with this,” notes Dr. Schweitzer. “In the next one to two years, you can expect to see a number of centers offering clinical trials.”

Tools for Epilepsy Management

One of Dr. Williams’ main interests is better management of epilepsy. He explained that he and his colleagues at Mass General enjoy access to a wide range of high-tech tools for working up seizures and treating the underlying disease. These include:

• Beneto encephalography, a very high-resolution form of intracranial electroencephalography that records activity in the cerebral cortex
• Positron emission tomography
• Functional imaging
• Responsive neurostimulators, which are “smart” stimulators implanted in the brain that allow a surgeon to detect seizures in real time
• Robot-assisted surgery, which allows neurosurgeons to implant electrodes very precisely, to localize where seizures are coming from
• Laser thermal ablation, a minimally invasive method in which laser light is administered through a very small pinhole to target a very specific area involved in producing seizures

All the innovative diagnostic devices are designed to be more precise and safer, says Dr. Williams. In that way, they better identify which patients with epilepsy are eligible for surgery and what procedure will benefit them most.

Bob Carter, MD, PhD, Chief of Neurosurgery at Mass General, states, "The greatest challenge we have is in getting the word out to both our patient and physician referring communities about all that we can offer patients, at even at an early stage of diagnosis. Our new minimally invasive therapies are both effective and safe, and they offer an additional strategy for our referring doctors and their epilepsy patients to consider."

These therapies can be done in conjunction with the patient’s existing team, and they permit the patient to quickly reintegrate into their usual routines and return to their existing physician for ongoing care after the procedure is completed. Dr. Carter adds, "The evaluation process is streamlined, and by offering a minimally invasive approach early in the patient’s course, we can improve a patient’s quality of life for many years ahead."

If a patient’s first antiepileptic medication doesn’t work and they try a second medication, the clinician should begin to think about referring to a comprehensive epilepsy center, Dr. Schweitzer advises. If a patient still has seizures despite being on two medications, then they should be referred to a comprehensive center for a work-up to see if they’re a candidate for surgery.

Brain-fused Spinal Neuroprosthetics

Many neurological disorders, such as motor paralysis and stroke, have little or no current treatment. Dr. Williams’ lab was the first to develop a functional cortical–spinal neural prosthetic “bypass” that is able to restore basic volitional motor control in a fully paralyzed limb.

This technology, which is still experimental, relies on the fact that most parts of the body are unaffected by damage to the central nervous system. After a spinal cord injury, for example, the brain, parts of the limbs and the nerves above and below the injury still function.

“We implant a small microchip in the part of the brain that’s responsible for thinking and planning, then put another microchip in part of the spinal cord below the injury,” Dr. Williams says. “In real time we record activity from the brain to predict what movement the individual is planning to make. Then through the other microchip, we stimulate the parts of the spinal cord or peripheral nerves that can generate that movement.”

Similar efforts by other researchers require patients to use a robotic arm, and that constrains the ability to move around freely, Dr. Williams observed. Using his lab’s technology, patients can control their own limbs.

Currently, the neuroprosthetics produce simple movements, such as raising a limb upward, but Dr. Williams is optimistic about the continued success of his research. “In theory you could recapitulate fairly naturalist movements if you have enough information and enough electrodes to record from.”

Dr. Schweitzer is even more confident about the future of stem cell–based therapy for Parkinson’s. “I’m at the stage now that when I talk to younger patients, I tell them that deep-brain stimulators are a bridge to the time when we will have the cure,” he says. “And if this cell-based therapy works for Parkinson’s disease, it will be applicable to other diseases, such as Alzheimer’s.”

Learn more about the Neurosurgery Department at Mass General

Learn more about the Cognitive Science Lab at Mass General