A new Parkinson’s disease treatment that adapts to the brain

The hallmark symptoms of Parkinson’s disease — shaky hands, muscle stiffness, slowed movements, and difficulty with balance — signify underlying irreversible damage to dopaminergic neurons in the brain. “Unfortunately, there is no cure for Parkinson's, and there are no disease-modifying therapies — meaning our treatments are only symptomatic,” said Suneil Kalia, a neurosurgeon and neuroscientist at the University of Toronto.

Kalia explained that currently, the two gold-standard treatments include medications that replace the lost dopamine in the brain and, for a subgroup of patients after the disease progresses, a surgical treatment called deep brain stimulation (DBS). In DBS, neurosurgeons like Kalia insert electrodes deep inside the brain — for Parkinson’s disease, they target the basal ganglia — that connect to wires under the skin that run to an implantable computer in the chest. Neurologists then program this device to send pulses of electrical current to reset abnormal brain rhythms and improve symptoms.

It is a very exciting advance, actually, and it's more physiologic so I think that's really going to take off.”
- Martin McKeown, University of British Columbia

Since the 1990s, classic DBS treatment has consisted of sending the same electrical pulses continuously day and night, regardless of what state the brain is in. But in February, the FDA approved the first adaptive system for Parkinson’s disease. Developed by Medtronic, this DBS device adjusts to the brain’s rhythms and sends personalized electrical pulses. The company had been developing the technology, called BrainSense™ Adaptive deep brain stimulation (aDBS), for over 10 years.

“What they've been able to do is … ramp up or ramp down the stimulation, depending upon the activity of the person or the brain state,” said Martin McKeown, a neurologist and engineer at the University of British Columbia. “It is a very exciting advance, actually, and it's more physiologic so I think that's really going to take off.”

The approval is based on Medtronic’s Adaptive DBS Algorithm for Personalized Therapy in Parkinson's Disease (ADAPT-PD) clinical trial, which evaluated the effectiveness and safety of two aDBS modes compared to continuous DBS. Results so far showed that compared to continuous DBS, the adaptive DBS system resulted in a clinically meaningful improvement in the amount of time that the patient felt that the device was working without a significant increase in adverse events (1).

Following the approval, Medtronic announced that the aDBS system will become the largest commercial launch of a brain-computer interface technology thus far. Kalia pointed out that the personalized nature of the aDBS system means that it will take even more time for neurologists to program the device for patients. In an attempt to address this concern, the approval also includes Medtronic’s BrainSense™ Electrode Identifier (EI), and Medtronic claims that the use of the EI allows clinicians to program the system 85 percent faster. However, Kalia believes this would only help identify parts of the electrode that might be best for classical stimulation, but he doesn't think this will reduce the time to program the adaptive stimulation.

Moving forward, Kalia and McKeown both agreed that the new aDBS system could have wide-ranging benefits for conditions beyond Parkinson’s disease too. “You could maybe tune the adaptation for different symptoms, so the tuning that's best for the motor system symptoms may be different than the tuning that's best for cognitive impairment or anxiety or other non-motor features,” said McKeown.

At the same time, Kalia noted that aDBS systems still do not modify the progression of Parkinson’s disease, and he’s hopeful that researchers will eventually discover a new treatment that does. “I always say that the goal of our lab is to put me out of business of doing these deep brain stimulation surgeries,” he said. “[Deep brain stimulation] has an amazing impact for our patients, but the disease is progressing. … We need therapies that slow down the course of the disease.” Kalia added that these therapies could take the form of oral pills or gene therapies delivered to the brain to slow down the loss of dopaminergic neurons. But he’s not ruling out that DBS or aDBS systems could turn out to be effective for this purpose too. “Is it possible to actually use DBS and adjust the stimulation in some way, to repurpose it, to slow down the loss of neurons?” he asked. Kalia said that his lab and others already have some preliminary data in this direction.

“That's another exciting area of investigation,” he said.

Reference