The US FDA has approved PharmaTher’s Investigational New Drug application to begin Phase 2 clinical trials for ketamine to treat levodopa-induced dyskinesia in patients with Parkinson’s disease.
Levodopa is an amino acid precursor of dopamine and is commonly used alongside carbidopa, an inhibitor of L-amino acid decarboxylase, to treat Parkinson's disease symptoms including tremor, muscle stiffness and slowness of movement.
Dyskinesia, characterized by rapid, involuntary and uncontrollable movements distinct from the typical tremors associated with Parkinson's, is a side effect of long-term levodopa use. Around half of the patients treated with the drug develop the condition within five years of initial treatment, and almost all patients develop it within ten years.
While dyskinesia can be localized to one part of the body, it can also spread to other areas. It can also affect speech, the respiratory tract, and the eye muscles in rare cases.
The underlying cause of dyskinesia from Levodopa is not currently known. However, it may be the result of fluctuations in dopamine caused by the drug, alongside a loss of dopaminergic neurons seen in those with Parkinson's.
In a retrospective analysis of patients with Parkinson’s disease, researchers found that those treated with ketamine for pain relief experienced an improvement in dyskinesia symptoms. Other studies have found that ketamine may also be able to treat pain and depression, other symptoms that are frequently found in those with Parkinson’s.
Having now received approval to commence Phase 2 trials investigating the effects of ketamine on Levodopa-induced dyskinesia, the researchers at PharmaTher plan on recruiting up to 36 subjects across eight clinical sites in the US. They will assess the patients according to changes in the Unified Dyskinesia Rating Scale over 8 weeks. They will also monitor total daily ‘off times’, periods when Parkinson’s symptoms return despite the use of medication, from 24-hour diaries.