Stephen H. Pasternak (Canada)
Parkwood Insitute/Western University
Cognitive Neurology and Alzheimer's Disease Research Centre
Dr. Stephen Pasternak is a Cognitive Neurologist (specialized in the diagnosis and treatment of neurodegenerative disease) and Director of the Cognitive Neurology and Alzheimer’s Disease Research Centre at Parkwood Institute and a Scientist at the Robarts Research Institute, at the University of Western Ontario (Western University). His laboratory at Robarts uses live cell imaging to understand lysosomal trafficking in Alzheimer’s disease, on blood biomarkers of neurodegenerative disease, and on harnessing protein clearance to treat neurodegenerative disease. At his clinic at Parkwood he sees patients with neurodegenerative disease including Alzheimer’s disease, Lewy Body disease and Parkinson’s Disease Dementia and participates in academic and industrial clinical trials including his own phase 2 trial of Ambroxol to treat Parkinson’s Disease Dementia.

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A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF AMBROXOL AS A DISEASE-MODIFYING TREATMENT FOR PARKINSON’S DISEASE DEMENTIA; BASELINE CHARACTERISTICS.

Session Name
1980 - ADVANCES IN PD AND LBD DRUG DEVELOPMENT 2 (ID 102)
Session Type
SYMPOSIUM
Date
Sun, 20.03.2022
Session Time
11:35 AM - 01:20 PM
Room
ONSITE: 114
Lecture Time
11:50 AM - 12:05 PM
Presenter

Abstract

Aims

Currently, there are no disease-modifying treatments for Synucleinopathies. Increasing the levels of α-Glucocerebrosidase (GCase; gene name GBA) lowers the levels of α-synuclein in cell and animal models and improves Parkinsonian symptoms. Ambroxol is an over the counter expectorant which is a pharmacological chaperone for GCase. This study aims to test the safety, tolerability and efficacy of Ambroxol in individuals with Parkinson’s Disease Dementia.

Methods

Our goal was to randomize 58 individuals with mild to moderate dementia (MoCA <=24, MMSE >=16) to Ambroxol 1050mg/day or placebo for 1 year. Primary outcome measures are the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog) and the ADCS Clinician’s Global Impression of Change (CGIC). Secondary outcomes include the UPDRS and a battery of cognitive and clinical assessments, and plasma/CSF and neuroimaging biomarkers. Pharmacokinetics and pharmacodynamics will also be examined.

Results

We have screened 70 candidates and 55 have been enrolled (94% of target). Enrollment is closed. So far 46 are at full dose, 34 have passed 6 months and 26 have completed a year. Mean MOCA at baseline was 19 and Mean MMSE was 25. Ambroxol has been well tolerated and there have been no SAE’s judged to be due to Ambroxol. We are achieving blood levels of 10-12 micromolar and CSF levels of about 0.7 μM. GCase levels in white blood cells is increased by 1.6 fold.

Conclusions

We are achieving Plasma and CSF levels predicted to be clinically useful. If found effective, Ambroxol will be the first disease-modifying treatment for PDD.

ClinicalTrial.gov NCT02914366. Funded by the Weston Brain Institute.

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