Click the play button for the audio version of this Research Summary
Why is it important?
- Novelty 80% 80%
- Proximity 80% 80%
- Deliverability 60% 60%
All participants underwent 5 clinical visits, at the start of the trial, then at days 11, 98, 186, and then after ambroxol dosing had ended at 279 days to assess wash out. They underwent several neurological tests and completed questionnaires on cognition and non-motor symptoms. In addition to blood samples, participants underwent a lumbar puncture for the collection of cerebrospinal fluid (CSF) which bathes the brain and so offers an array of direct chemical insights into brain metabolism. CSF was collected at baseline and at the end of the study.
Ambroxol was well tolerated and the reported adverse events related to gastrointestinal disturbances and a transient skin condition in one patient. The analyses showed that by day 186, ambroxol had penetrated the brain as indicated by its levels in CSF, and reduced GCase activity – counterintuitively, ambroxol has been shown to reduce free GCase activity in fluid that contains no cells, but increases it when applied to neurons. Levels of alpha synuclein in CSF also increased, potentially indicating enhanced neuronal GCase activity resulting in better clearance, or expulsion, of alpha synuclein into CSF. Some improvements were seen in movement using the Unified Parkinson’s Disease Rating Scale (UPDRS part III), although these did not persist after the drug dosing ended, and are difficult to interpret as no placebo arm was included.