Study Rationale:
Motor symptoms of Parkinson’s disease are caused by a lack of brain neurons that carry a neurotransmitter called dopamine, and are commonly treated with levodopa. However, after several years of treatment, many patients develop side effects such as uncontrolled jerky movements, called dyskinesia, that negatively impact quality of life. Recent studies show that dyskinesia is associated with another brain neurotransmitter, called serotonin. Inhibition of serotonin neurons is a promising strategy to treat dyskinesia and can be achieved using drugs such as NLX-112. Experiments in pre-clinical models of Parkinson’s disease show that NLX-112 is effective in reducing dyskinesia, while maintaining the antiparkinsonian activity of levodopa.
Hypothesis:
The hypothesis being tested is that NLX-112, a drug that targets brain serotonin neurons by specifically activating 5-HT1A receptors, will be safe and well-tolerated in patients with Parkinson’s disease and that it will reduce their levels of levodopa-induced dyskinesia.
Study Design:
A total of 24 patients with moderate to severe Parkinson’s disease will be allocated to one of two treatment groups: placebo or NLX-112. Treatments will be taken twice per day, once in the morning and once in the evening for eight weeks. Patients will be carefully monitored to assess the safety and tolerability of NLX-112 and to determine whether it reduces the patients’ levels of dyskinesia in response to levodopa treatment. This will be done using standard scoring methods, as well as wearable devices. Other parameters of the patients’ condition, such as mood and sleep, will also be assessed.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
If the trial is successful, it will provide support for specifically targeting serotonin 5-HT1A receptors on brain serotonin neurons to diminish levodopa-induced dyskinesia in Parkinson’s disease. Moreover, it will provide important information concerning the safe and effective doses of NLX-112 that can be tested in larger clinical trials.
Next Steps for Development:
The next step in the development of NLX-112 will be to carry out advanced clinical trials involving larger numbers of patients. If these confirm the findings of the present study, they will lead up to preparation of a regulatory application to the FDA for approval as a novel drug.
Trial Phase:
Phase IIa