A landmark Phase 3 clinical trial is beginning in the UK, testing whether a common cough medicine can be used to treat Parkinson's disease. Early studies indicate the 50-year-old drug can cross into the brain and help clear out the toxic proteins known to cause Parkinson's.
Around a decade ago, researchers were investigating novel treatments for a condition known as Gaucher disease. The rare genetic disorder leaves people deficient in an enzyme called glucocerebrosidase (or GCase). Screening hundreds of already approved drugs, researchers discovered a common ingredient in cough syrup called ambroxol increased the activity of GCase.
Following this discovery, Parkinson's disease researchers took note. Low levels of GCase in the brain have been implicated in the pathology of Parkinson's as the enzyme plays a crucial role in helping the brain clear out toxic proteins.
Up to 15% of people with Parkinson's disease carry a specific gene mutation which reduces production of GCase, and many Parkinson's patients without the gene mutation still show unusually low levels of GCase. So if ambroxol increases GCase activity, could it work as a treatment for Parkinson's?
Preclinical tests were promising and it quickly became plausible the drug could potentially help Parkinson's patients. But two questions remained – does enough of the drug cross the blood-brain barrier in humans to be effective, and can patients tolerate the doses necessary for the drug to be therapeutically effective?
A Phase 2 human trial promisingly answered those questions, finding ambroxol was safely tolerated at high enough doses to enter the brain and increase GCase levels. The research, published in 2020, also showed ambroxol lowered levels of the toxic protein alpha-synuclein in Parkinson's patients and potentially improved motor symptoms.
All of this has paved the way for a crucial Phase 3 trial, beginning this year in the UK. The trial plans to recruit 330 Parkinson's patients, offering each subject either ambroxol or a placebo for two years.
"This will be the first time a drug specifically applied to a genetic cause of Parkinson’s disease has reached this level of trial and represents 10 years of extensive and detailed work in the laboratory and in a proof of principle clinical trial," explained lead investigator on the trial Anthony Schapira.
It's hoped by 2025 the trial will offer some insights into whether this common cough medicine drug can benefit patients with Parkinson's diseases. Will Cook, from charity Cure Parkinson's, said his organization is working on helping fund trials such as this one to rapidly bring new treatments to the clinic.
“This trial is a big step forward in the search to find new treatments for Parkinson’s," said Cook. "Once the ambroxol trial is underway, it will be one of only six Phase 3 trials on public record of potentially disease-modifying drugs in Parkinson’s, worldwide."
Source: UCL
