February 2024 issue
February 29, 2024 | The neurotechnology market opportunity for treating Parkinson’s disease has been dominated by deep-brain stimulation systems. But in recent months, some new neurotech therapies exploiting other forms of neuromodulation have emerged from two research teams in Asia.
A team of researchers from Japan has developed a novel neuromodulation approach that features gait-combined closed-loop transcranial electrical stimulation. The team demonstrated significant gait improvements in patients with various neurological disorders including PD.
Gait disorders in PD manifest as decreased step length, reduced arm swing, slow movements, rigidity, and postural instability. While non-pharmacological approaches like transcranial direct current stimulation show promise in improving motor function, this new research focuses on gait-combined closed-loop stimulation, which synchronizes brain stimulation with the individual’s gait rhythm. A recent study published in the Journal of Neurology, Neurosurgery & Psychiatry proposes a novel intervention for gait improvement, thus creating new hope for patients with PD.
“We recently developed a novel neuromodulation approach using gait-combined closed-loop transcranial electrical stimulation and demonstrated promising gait improvements in patients who are post-stroke. Here, we tested the efficacy of this intervention in patients with Parkinsonian gait disturbances,” said lead author Ippei Nojima from Shinshu University and Nagoya City University, Japan.
To this end, the clinical researchers from Japan recruited 23 patients with PD or Parkinson’s syndrome. All study participants were randomly assigned to receive either the active treatment or a “sham” treatment that mimics the active treatment but does not offer any therapeutic benefit.
During the course of the trial, an electrode carrying a low current (up to 2 mA) was externally affixed to the occipital region of the head. A reference electrode was then placed in the neck region to establish a stable electrical reference point and to complete the electrical circuit. The treatment included performing tES on the cerebellum in a noninvasive manner. The brain side showing severe impact was specifically targeted during the electrotherapy.
“Gait disturbance lowers activities of daily living in patients with PD and related disorders. However, the effectiveness of pharmacological, surgical, and rehabilitative treatments is limited. Our novel intervention might be able to improve physical function for not just patients with PD but also for those with other disabilities,” said senior author Yoshino Ueki from the department of rehabilitation medicine at Nagoya City University.
The cerebellum plays a key role in gate control. Therefore, electrical stimulation of this region is likely to exert therapeutic benefits. The therapy showed encouraging results after just 10 repetitions. The treatment group showed a significant improvement in gait parameters including speed, gait symmetry, and stride length. “These findings showed that gait-combined closed-loop tES over the cerebellum improved Parkinsonian gait disturbances, possibly through the modulation of brain networks generating gait rhythms,” said Nojima.
Interestingly, no patient dropped out during the study. Moreover, patients from both the groups (treatment and sham) showed good and comparable compliance. Side effects such as skin irritation, vertigo, or odd sensations/perceptions were also not observed in any of the volunteering patients. This study has special significance, considering the fact that Japan is witnessing a sharp rise in its elderly population.
“Patients with impacted gait have restricted daily activities. We successfully developed a new non-pharmacological and noninvasive intervention for the rehabilitation of patients with PD and other neurological disorders. Our breakthrough method could be used to restore gait in these patients,” said Ueki.
Although the study has certain limitations, it suggests that the personalized brain stimulation, synchronized with individual gait rhythm, can effectively enhance gait function in PD and has the potential to be used as an adjunct therapy for gait rehabilitation.
Another team of researchers from the Institute for Basic Science in South Korea recently reported in ACS’ Nano Letters on a new form of neuromodulation, called magnetogenetics, that uses very small magnets to wirelessly trigger specific, gene-edited nerve cells in the brain. The treatment effectively relieved motor symptoms in mice without damaging surrounding brain tissue.
In traditional DBS, a battery pack externally sends electrical signals through wires, activating nerve cells in the subthalamic nucleus. STN activation can relieve motor symptoms of PD, including tremors, slowness, rigidity, and involuntary movements. However, because the potential side effects, including brain hemorrhage and tissue damage, can be severe, DBS is usually reserved for people who have late-stage Parkinson’s disease or when symptoms are no longer manageable with medication. In a step toward a less invasive treatment, Minsuk Kwak and Jinwoo Cheon worked with their colleagues to develop a wireless method to effectively reduce motor dysfunction in people with Parkinson’s disease.
For their wireless technique, the researchers tagged nanoscale magnets with antibodies to help the molecules “stick” to the surface of STN nerve cells. Then they injected the sticky magnets into the brains of mice with early- and late-stage Parkinson’s disease. Prior to the injection in the STN, those same nerve cells had been modified with a gene that caused them to activate when the modified magnets on the cell’s surface twisted in reaction to an externally applied magnetic field of about 25 milliteslas, which is about one-thousandth the strength of an MRI.
In demonstrations of the magnetized and modified neurons in mice with Parkinson’s disease, the mice exposed to a magnetic field showed improved motor function to levels comparable to those of healthy mice. The team observed that mice that received multiple exposures to the magnetic field retained more than one-third of their motor improvements while mice that received one exposure retained almost no improvements. Additionally, the nerve cells of treated mice showed no significant damage in and around the STN, which suggests this could be a safer alternative to traditional implanted DBS systems, the researchers say. The team believes its wireless magnetogenetic approach has therapeutic potential and could be used to treat motor dysfunction in people with early- or late-stage PD as well as other neurological disorders, such as epilepsy and Alzheimer’s disease.
