Good news for the treatment of Parkinson’s Disease may be on the near horizon after a British scientific study on ambroxol, the active ingredient in cough suppressants, showed amazing results.
University College in London sponsored the clinical trial in collaboration with the UK’s Cure Parkinson’s Trust, the Van Andel Research Institute’s shared funding initiative, the John Black Charitable Foundation, and an independent leading Czech pharmaceutical company called PRO.MED.CS Praha a. s.
The researchers set out to “evaluate the safety, tolerability and pharmacodynamics of ambroxol in participants with Parkinson Disease.” Pharmacodynamics is the study of the biochemical and physiologic effects of drugs.
Ambroxol has been a common additive to commercial cough syrups since the 1980s to break up phlegm (“flem”). The new findings indicate that this ready medicine helps reduce levels of alpha-synuclein (“AL-fa-sigh-NEW-klee-in”), a toxic protein, in neurons – one of the key characteristics of Parkinson’s Disease (PD).
PD patients with the single GBA gene mutation are at a higher risk for developing Parkinson’s. They have an inherited predisposition (likelihood) to develop impaired movement when younger, display more cognitive dysfunction, and experience a faster progression of the disease.
GBA gene mutations occur in about 10 percent of PD cases and are the biggest genetic risk factor for the disease. They cause dysfunction in the naturally-occurring enzyme protein glucocerebrosidase (“GLU-co-seh-REE-bro-sih-DAZE”), abbreviated as GCase, which can create a build-up of alpha-synuclein. The enzyme GCase can reduce the growth of cells that cause PD.
Ambroxol has been demonstrated to improve the function of GCase in nerve cells, which helps reduce the accumulation of alpha-synuclein. The scientists wanted to see if reducing these aggregated clumps of alpha-synuclein in neurons would slow the progression of PD.
The proof-of-concept study, led by Dr. Anthony Schapira, MD, DSc, at the Royal Free Hospital, was called AiM-PD. Over 24 months, 18 people with the genetic form of PD received ambroxol at five dose levels. Clinical assessments, lumbar punctures, venepuncture, biomarker blood analysis, and cognitive assessment were tracked throughout the course of the study.
Schapira shared his team’s positive news:
“The results of the AiM-PD study indicate that ambroxol is safe, well-tolerated, and able to increase GCase levels in the spinal fluid of people with Parkinson’s. This is an important step to now allow us to find out whether this drug can slow the progress of Parkinson’s.”
The clinical trial was open-label, the kind where study details are shared with the participants. Unlike a blinded trial where study information is withheld to reduce bias, both the researchers and participants know which treatment is being administered.
An open-label approach was used because each patient self-administered the study drug ambroxol (60 mg per tablet) at 5 intra-dose escalations over the course of 6 months – from January 2017 to April 2018 – as shown below:
Day 1-7: 60 mg three times a day
Day 8-14: 120 mg three times a day
Day 15-21: 180 mg three times a day
Day 22-28: 300 mg three times a day
Day 29-186: 420 mg three times a day
The researchers noted that previous studies showed that ambroxol can penetrate the brains of rodents and non-human primates and may slow the progression of Parkinson’s Disease.
By analyzing the cerebrospinal fluid, blood, and urine samples of 17 patients before, during, and after the drug had been taken for a 6-month period, the researchers concluded that the GCase enzyme was stimulated, producing measurably higher levels after the ambroxol crossed the blood-brain barrier.
The findings also showed that ambroxol crossed the blood-brain barrier and bound to the GCase enzyme.
This research backs up previous human and animal studies from University College London (UCL) that showed ambroxol can increase GCase proteins in cerebrospinal fluid by about 35 percent while simultaneously reducing alpha-synuclein levels.
Simon Stott, PhD, of The Cure Parkinson’s Trust in London, explained the importance of this information:
“The ambroxol study is important because there are no treatments available for Parkinson’s that slow, stop, or reverse [it]. All of the current medications only deal with the symptoms of the condition – they do nothing to delay the progression of Parkinson’s.”
The study sponsors are now exploring the next steps in the development of this new therapeutic approach to conquer Parkinson’s.