Ketamine could potentially provide relief for Parkinson's disease-related Dyskinesia
In a groundbreaking discovery, researchers have found that ketamine, commonly known as an anesthetic or a treatment for depression, could offer a promising new approach to managing levodopa-induced dyskinesia (LID) in Parkinson's patients.
Traditionally, LID was believed to be a result of dopamine receptor dysregulation in the basal ganglia due to prolonged levodopa treatment. However, the new understanding emphasizes that motor cortex circuitry disruptions also play a central role in LID.
Ketamine helps restore neural control in Parkinson’s patients with LID primarily by modulating motor cortex dysfunction through its action as an NMDA receptor antagonist. This reduces the abnormal overactivity and neural circuit disruptions caused by long-term levodopa use, leading to a reduction in involuntary movements without inducing anesthesia at low doses.
The motor cortex is not generating unwanted movements in Parkinson's patients with LID. Instead, the neural activity in the motor cortex shows almost no correlation with the uncontrollable movements. The first mechanism of ketamine's influence is disrupting the abnormal repetitive electrical patterns occurring during dyskinesia. The second mechanism is triggering slower processes involving neuroplasticity, which allows the motor cortex to gradually reassert control over movement.
This second-phase effect of ketamine allows for improvement in the quality of life for Parkinson's patients for weeks or even months after treatment. A single dose of ketamine can provide long-lasting benefits for up to several months. Early results from the clinical trial show some patients experiencing benefits that last for weeks after a single course of treatment.
The study, which received funding from the National Institute of Neurological Disorders and Stroke and the Arizona Biomedical Research Commission, fundamentally changes how we think about the relationship between brain activity and movement in Parkinson's disease.
Researchers are exploring other compounds and non-pharmacological approaches to promote motor cortex reconnection without ketamine's dissociative effects. The traditional approach to managing dyskinesia has been unsuccessful due to an incorrect understanding of its causes. This research publication offers renewed hope for Parkinson's patients suffering from dyskinesia, as it suggests potential ketamine-based therapies.
A Phase 2 clinical trial at the University of Arizona is testing low-dose ketamine infusions for dyskinesia in Parkinson's patients. The differences between the traditional understanding and ketamine's mechanism and new understanding are summarized as follows:
| Aspect | Traditional Understanding | Ketamine’s Mechanism and New Understanding | |--------|---------------------------|-------------------------------------------| | Primary cause of dyskinesia | Dysregulated dopamine receptor signaling in basal ganglia | Disrupted motor cortex activity and glutamatergic NMDA receptor overactivation | | Target for therapy | Dopamine pathways | NMDA receptors and cortical motor circuits | | Effect of ketamine | Not traditionally used for LID | Reduces dyskinesia by normalizing cortical control, reducing involuntary movements at sub-anesthetic doses |
Thus, ketamine restores movement control not by directly replacing dopamine but by rebalancing cortical neural activity disrupted in Parkinson’s patients on levodopa, offering a promising and different approach to managing LID.
Therapies and treatments using ketamine for neurological disorders such as Parkinson's disease are being explored, as ketamine could offer a unique and effective approach to managing levodopa-induced dyskinesia (LID). Instead of focusing solely on regulating dopamine receptor signaling, as traditionally believed, the new understanding emphasizes the importance of rebalancing cortical neural activity, particularly in the motor cortex, to manage LID effectively.
