Cough medicine ambroxol shows promise in slowing Parkinson’s dementia

Cough medicine ambroxol shows promise in slowing Parkinson’s dementia

LONDON: A small but groundbreaking study published in JAMA Neurology has found that ambroxol, a common cough medicine, may help slow cognitive and neuropsychiatric decline in patients with Parkinson’s disease dementia (PDD), particularly in those with specific GBA1 gene mutations.

The randomized clinical trial, led by Dr. Stephen H. Pasternak, a neurologist and dementia researcher, assessed ambroxol’s safety, tolerability, and impact on brain function in patients with PDD. The study involved 55 participants, all over the age of 50 and diagnosed with Parkinson’s disease for at least one year prior to the onset of dementia.

Ambroxol linked to stable neuropsychiatric symptoms

Patients were randomly assigned to receive either high-dose ambroxol (1,050 mg/day) or a placebo for one year. While primary and secondary cognitive outcomes were similar between the two groups, patients on placebo showed worsening neuropsychiatric symptoms, such as behavioral changes and agitation, while those on ambroxol remained stable.

Dr. Pasternak noted:

“Patients on ambroxol had fewer psychiatric symptoms and better preservation of cognitive function, especially those with GBA1 gene variants.”

Targeting GBA1 gene and brain enzyme activity

Ambroxol is believed to work by increasing levels of beta-glucocerebrosidase (GCase), an enzyme that helps with lysosomal function in brain cells. This is particularly relevant in Parkinson’s patients with GBA1 mutations, which are linked to faster cognitive decline.

In fact, participants with GBA1 variants who took ambroxol showed:

• Clinically meaningful improvements in cognition
• Decreased neuropsychiatric symptoms
• Increased GCase activity at 26 weeks

These early findings suggest ambroxol could be a disease-modifying therapy, offering more than just symptomatic relief.

Safety and tolerability outcomes

Ambroxol was generally well-tolerated. The most common side effects in the ambroxol group were gastrointestinal issues, while the placebo group saw more psychiatric events and falls. Despite some participants withdrawing from the study, the majority completed the 12-month trial.

A promising path, but more research needed

The authors emphasized that this phase 2 study was relatively small, had recruitment challenges, and included mostly white male participants with mild to moderate dementia. Furthermore, the study did not include data from the planned low-dose ambroxol group due to insufficient enrollment.

Only eight participants carried GBA1 mutations, so while results are encouraging, larger and longer-term trials are necessary to confirm ambroxol’s benefits.

Expert perspectives and future implications

Dr. Daniel Truong, a neurologist and editor-in-chief of the Journal of Clinical Parkinsonism and Related Disorders, commented on the study:

“This could mark a shift toward targeted disease modification in Parkinson’s dementia. Ambroxol’s known safety and wide use as a mucolytic drug make it an ideal candidate for repurposing.”

However, ambroxol is not yet approved by the U.S. FDA for neurological use. Still, if future studies replicate these results, it could lead to faster regulatory approval and accessibility in resource-limited settings.

Dr. Pasternak and his team plan to launch a follow-up clinical trial later in 2025, funded by the Garfield Weston Foundation in the U.K.

“Current therapies only manage symptoms. Ambroxol may offer a new avenue to protect brain function, especially in genetically at-risk patients,” Pasternak said.

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