AD/PD 2022 | Phase II trial of ambroxol as a disease modifying therapy for Parkinson’s disease dementia

Mutations in the GBA gene, resulting in impaired glucocerebrosidase activity, are the single largest genetic risk factor for idiopathic Parkinson’s disease (PD) development, thought to occur in 5-10% of all Parkinson’s cases. The associations of GBA mutations with dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) have also been well established. Ambroxol was identified in drug screening studies as an agent of interest on account of its action as a small molecule chaperone able to increase glucocerebrosidase activity. Stephen Pasternak, MD, PhD, FRCPC, Robarts Research Institute, Western University, London, Ontario, Canada, discusses a Phase II trial (NCT02914366) investigating the safety and efficacy of ambroxol in patients with PDD. A total of 55 patients have been enrolled and randomized to receive high dose ambroxol (1050mg/day) or placebo for 1 year. To date, no serious adverse events attributable to ambroxol use have occurred, and plasma and cerebrospinal fluid (CSF) drug levels have been achieved that are predicted to be clinically useful. This interview took place at the AD/PD™ 2022 Conference in Barcelona, Spain.