Neurology 2024: Targeted Plasticity Therapy and New Targets
Targeted plasticity therapy (TPT) is a bioelectronic medicine segment in the medical device market that uses neurostimulation and neuromodulation to treat upper limb dysfunction. It uses Vegas nerve stimulation and training nerves as rehabilitation enhancers. The therapy has been discovered to work in preclinical models of spinal cord injury and is currently in clinical trial. Labs are exploring new techniques, approaches, and targets for targeted plasticity therapy.
Bioelectronic medicine is a treatment approach that offers a more efficient and effective alternative to pharmacological medicines. Bioelectronic medicines stimulate neural tissue, such as peripheral nerves, brain, and spinal cord, to deliver therapeutically relevant molecules. This approach allows for immediate and potentially rapid release of these molecules, reducing side effects and allowing for better spatial and temporal control. By stimulating specific nerves, bioelectronic medicines can directly modulate the target organ or tissue, reducing side effects and allowing for rapid termination of stimulation. This approach offers better spatial and temporal control over traditional medicines.
Bioelectronic medicines, specifically vagus nerve stimulation (VNS), are used for targeted plasticity therapy. VNS is implanted on the left cervical vagus with a pulse generator and is FDA-approved for four conditions: depression, epilepsy, obesity, and stroke rehabilitation. It uses molecular release to facilitate neuroplasticity, allowing the brain and neural circuits to change. By stimulating the vagus, 90% of fibres are afferents, releasing acetylcholine and norepinephrine, which play a significant role in modulating synaptic connectivity and rewiring broken circuits after damage.
TPT is a treatment that targets specific neural activity to promote the plasticity of circuits before or after injury. TPT uses a half-second stimulation to target specific events, such as motor and sensory connections, to double or triple brain connections to activated muscles. This spatially precise technique requires careful timing and targeting of other neurotransmitters. TPT has been used to enhance connectivity and function after neural injuries, such as spinal cord injuries or strokes. The therapy has rewired the primary auditory cortex, reduced tinnitus symptoms, and targeted movements. The therapy is currently in phase two clinical trials. TPT has shown promise in rehabilitating damaged brains and enhancing function.
Neuronal maps show muscle-specific activation and plasticity before injury, suggesting the potential to rewire the motor system. This motor-targeted plasticity therapy could be used after injury, particularly in models of ischemic stroke. The study also showed that recovery can be enhanced even after neural damage by rewiring spare neural circuits, a preclinical model that is now being explored in clinical trials. The therapy works after peripheral nerve injury and has various events and targets in the motor realm.
The study investigates the effectiveness of upper limb rehabilitation after spinal cord injury. Animals are trained to perform an operant conditioning task, allowing forelimb strength tracking and recordings of good motor activity. The study compares vagus nerve stimulation with traditional upper limb rehabilitation, commonly done in humans post-injury. The goal is to increase neural activity and muscle connections, compared to the conventional rehabilitation treatment alone.
The study presents preliminary evidence that targeted neuromuscular stimulation (VNS) and rehabilitation therapy can improve forelimb strength in individuals with cervical spinal cord injuries. The study found that the combination of VNS plus rehab and targeted plasticity therapy significantly increased forelimb strength over six weeks, demonstrating that this could work after a spinal cord injury. The study also showed that post-injury neuroplasticity was promoted through intracortical microstimulation and brain mapping of the motor cortex. The animals that received hundreds or over a thousand good movements paired with Vegas nerve stimulation had four times more brain area connected to the paralyzed distal forelimb muscles, likely facilitating increased recovered strength. Trans synaptic tracing was used to examine the neuroanatomical aspects of the circuits connected to the paralyzed muscles. The study suggests that the neuron access plasticity may rely heavily on the motor cortex rather than sub-vertically. This exciting development has led to a phase 1 clinical trial for individuals with cervical spinal cord injuries.
The clinical spinal cord injury trial introduced a miniaturized stimulation device that runs through Android systems and uses sensorized objects to enhance upper limb rehabilitation. The device is placed on the Vegas nerve and triggers using a scarf around the neck. The device is reimbursed for six weeks of therapy, but more movement pairings may be needed for maximum recovery. The University of Miami is a site in the pivotal trial, and the FDA has approved it for phase 3. The device is expected to be used in at-home sessions and contribute to rehabilitation efforts.
9th Edition of International Conference on Neurology and Neurological Disorders June 20-22, 2024, Paris, France
