Parkinson’s disease (PD), a debilitating neurological condition, significantly impacts the lives of those affected, particularly in its advanced stages. The disease is characterised by severe locomotor deficits, including gait impairments and balance issues, often unresponsive to existing treatments such as dopamine replacement therapies and deep brain stimulation (DBS) of the subthalamic nucleus.
Researchers have now developed a groundbreaking neuroprosthesis designed to alleviate these locomotor deficits. This device operates in a closed loop, targeting the dorsal root entry zones in the lumbosacral spinal cord to replicate the natural activation patterns during walking. This innovative approach could redefine treatment options for Parkinson’s disease, particularly in its later stages. The findings were published in Nature Medicine.
The journey to this discovery began with the creation of a preclinical model using non-human primates (NHPs) treated with MPTP, a compound that induces Parkinson-like symptoms. This model helped in understanding the locomotor deficits akin to those seen in humans with Parkinson’s. Researchers found that both NHPs and human patients displayed similar gait impairments and balance problems, validating the use of NHPs as an effective model for developing the neuroprosthesis.
The neuroprosthesis is based on epidural electrical stimulation (EES) targeting specific leg motor neurons. The device’s development involved detailed analyses of the natural activation patterns in NHPs and how these were altered by Parkinson’s. This led to the creation of electrode arrays tailored to target key areas in the spinal cord involved in walking.
The first application of the brain-controlled neuroprosthesis was in NHPs. It involved integrating motor cortex activity with EES bursts, establishing a digital bridge between the brain and spinal cord. This approach successfully alleviated gait impairments and balance problems in MPTP-treated NHPs. Notably, it also improved their posture and skilled locomotion abilities, like navigating a horizontal ladder.
The neuroprosthesis was also tested in combination with DBS, showing that it could complement DBS in addressing the range of motor signs associated with PD. In NHPs, this combination led to enhanced mobility and alertness, as well as improved gait and balance.
Transitioning to human trials, researchers established the feasibility of decoding motor intentions from cortical activity in people with PD. This was critical for the synchronization of EES with ongoing movements. A 62-year-old male patient with a 30-year history of PD and severe locomotor deficits was enrolled in the STIMO-PARK clinical trial. Despite DBS and medication, the patient faced significant challenges, including frequent falls.
The neuroprosthesis, tailored to the patient’s spinal cord anatomy and locomotor requirements, showed significant improvements. It re-established the natural activation of leg motor neurons during walking, effectively complementing existing treatments like DBS and medication. This led to improvements in gait symmetry, stride length, balance, and a reduction in freezing episodes.
This novel neuroprosthesis represents a significant leap in treating Parkinson’s disease, particularly in its advanced stages. It offers a new avenue of hope for patients who have been unresponsive to existing treatments, promising an improved quality of life and greater independence.
