In Early Trial, Ambroxol Shows Promise for Parkinson Disease Dementia
A drug used in Europe for treating respiratory conditions was safe, well-tolerated, and demonstrated target engagement in patients with Parkinson disease dementia (PDD). The findings, published in JAMA Neurology, could be used to support larger trials investigating ambroxol as a potential disease-modifying treatment for PDD.
“This early trial offers hope and provides a strong foundation for larger studies,” said lead author Stephen Pasternak, MD, PhD, a cognitive neurologist at the Lawson Research Institute of St. Joseph's Health Care London, London, Ontario, Canada, in a news release.
Approved for respiratory conditions in Europe, ambroxol is not currently approved for any use in Canada or the United States. However, during a fellowship at The Hospital for Sick Children in Toronto, Ontario, Canada, Dr Pasternak learned about ambroxol as a potential treatment for a rare genetic disorder called Gaucher disease, which is caused by a deficiency of the enzyme glucocerebrosidase (GCase).
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Patients with Parkinson disease often have low levels of GCase as well, which can cause waste build-up and eventual damage in brain cells. Ambroxol supports GCase, leading Dr Pasternak to investigate whether it could help patients with PDD.
The phase 2, double-blind study randomized 55 patients with PDD at a single center to daily ambroxol or placebo for 52 weeks. Researchers monitored adverse events, memory, psychiatric symptoms, and glial fibrillary acidic protein (GFAP), a blood marker associated with brain damage, in participants.
According to the findings, ambroxol was safe, well-tolerated, and reached therapeutic levels in the brain. Although patients who received placebo experienced clinically meaningful worsening in psychiatric symptoms, patients who received placebo remained stable. Additionally, GFAP levels increased in the placebo group but not in the ambroxol group, suggesting a potential for brain protection with ambroxol.
Patients with high-risk variants of the GBA1 gene, which produces GCase, demonstrated improved cognitive performance with ambroxol, researchers reported.
“Current therapies for Parkinson disease and dementia address symptoms but do not stop the underlying disease,” Dr Pasternak said. “These findings suggest ambroxol may protect brain function, especially in those genetically at risk. It offers a promising new treatment avenue where few currently exist.”
The research team plans to begin a follow-up trial focused specifically on cognition later this year.
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