University College London-Led Study Reveals Ambroxol Evidences Promise as Parkinson’s Disease Drug

University College London-Led Study Reveals Ambroxol Evidences Promise as Parkinson’s Disease Drug

A team led by University College London Institute of Neurology discovered ambroxol therapy could be used as a neuroprotective compound to treat patients with Parkinson’s disease both with and without glucocerebrosidase (GBA1) gene mutations.

This study was sponsored by University College London and included collaborators, including the UK’s Cure Parkinson’s Trust and PRO.MED.CS Praha a.s., a pharmaceutical company from the Czech Republic.

The Drug

Ambroxol is a drug that breaks up phlegm, used in the treatment of respiratory diseases associated with viscid or excessive mucus. Recently, a hypothesis suggested that it may have a potential role in the treatment of Paget’s disease of bone, Parkinsonism, and other common diseases of aging-associated ailments involving dysfunction of autophagy. Ambroxol is often administered as an active ingredient in cough syrup. It was patented back in 1966 and came into medical use in the 1970s.

The Study

The clinical trial was conducted between 2017 and 2018 at the Leonard Wolfson Experimental Neuroscience Centre, a clinical research facility that is part of the University College London Queen Square Institute of Neurology. A Phase II study, the sponsor sought to evaluate the safety, tolerability, and pharmacodynamics of ambroxol in participants with Parkinson’s Disease. Participants will administer ambroxol at five dose levels and will undergo clinical assessments, lumbar punctures, venipuncture, biomarker blood analysis, and cognitive evaluation throughout the study.

The investigators and staff identified actual study participants from the Royal Free London Hospital and National Hospital for Neurology and Neurosurgery in London.

This study involved an open-label clinical trial, including 17 Parkinson’s disease patients. The clinical investigators uncovered that ambroxol crossed the blood-brain barrier and bound to the β-glucocerebrosidase (GCase) enzyme and in the process, increasing β-glucocerebrosidase enzyme protein levels and cerebrospinal fluid (CSF) α-synuclein levels in participants with or without glucocerebrosidase gene mutations.

The team sought to detect ambroxol in the cerebrospinal fluid GCase activity at 186 days. The results of the study, “Ambroxol for the Treatment of Patients With Parkinson Disease With and Without Glucocerebrosidase Gene Mutations,” was published online in JAMA Neurology.


The study team sought the primary outcomes of the detection of ambroxol in the cerebrospinal fluid GCase activity at 186 days. While assessing the cerebrospinal fluid, the study team found a 156-ng/mL increase in ambroxol. And they observed increases in treatment to 50pg/mL (13%) in the CSF α-synuclein concentration (95% Cl, 14-87; P=.01) and increase of 88 ng/mol (35%) in the CSF GCase protein levels (95% Cl, 40-137; P=.002) was observed, reports Kenny Walter, with MDMag.

Walter reports that the study team found that the patients overall tolerated the new therapy with no serious adverse events. There were 176 adverse events, and 121 of them were deemed unrelated while 32 were unlikely related, leaving 15 possible related; 5 related and only three were certainly related to the treatment. The main adverse events included nausea, vomiting, and a burning sensation after consuming the medicine and a transitory skin issue on the chest, back and arms.                                                                                                                                                                   

Overall the study results point out that ambroxol therapy is safe and well-tolerated—moreover, “the CSF penetration and target engagement of ambroxol were achieved, and CSF α-synuclein levels were increased,” reported the authors.

The authors continued that “placebo-controlled clinical trials are needed to examine whether ambroxol therapy is associated with changes in the natural progression of Parkinson’s disease.”

MDMag reported that mutations of the glucocerebrosidase gene might trigger the autosomal recessive lysosomal storage disorder or Gaucher disease. The study team notes that in vitro and in vivo, studies reveal ambroxol increases β-glucocerebrosidase enzyme activity while reducing α-synuclein levels. A genetic risk factor for Parkinson’s disease, these mutations exhibit penetration of 10-30% and are present in 5-15% of Caucasian patients with Parkinson’s disease, 25% of Ashkenazi Jewish patients with Parkinson’s disease and only 1% of individuals without the disease.

Lead Research/Investigator

Stephen Mullin, PhD, Department of Clinical and Movement Neurosciences, University College London Institute of Neurology