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Parkinson’s disease (PD) is a progressive and complex neurodegenerative disorder that affects movement. It is narked not only by motor symptoms – such as tremors, stiffness, and bradykinesia – but also by cognitive decline. PD is also characterized by the degeneration and death of nerve cells in the brain that produce dopamine, a chemical messenger crucial for smooth and coordinated muscle movements. This loss of dopamine leads to a variety of motor and non-motor symptoms. Moreover, up to half of people with PD develop Parkinson’s disease dementia (PDD) within a decade, with symptoms ranging from memory loss and confusion to hallucinations and mood disturbances.Recently, a groundbreaking phase 2 clinical trial has revealed that a common cough medicine can stabilize psychiatric symptoms and potentially slow cognitive decline in PDD patients.Read on to know more.

The recent discovery

According to a clinical trial, Ambroxol, a common cough medicine (used in Europe), has shown promise in slowing cognitive decline in people with Parkinson’s disease dementia.

A 12-month study conducted by researchers at Lawson Research Institute found that Ambroxol helped stabilise psychiatric symptoms, improved cognitive function, and protected against brain damage in genetically at-risk participants.The study published in JAMA Neurology compared the outcome of the expectorant Ambroxol with a placebo among participants with Parkinson’s disease dementia.While primary and secondary outcomes were similar, participants on the placebo experienced worsening neuropsychiatric symptoms compared to symptoms remaining the same in the intervention group.The results also showed a possible improvement in cognitive symptoms for people with variants of a particular gene.

Understanding Parkinson’s Dementia

Parkinson’s disease dementia is a progressive condition superimposed on the classic movement symptoms of PD. It typically manifests in the later stages of the disease and includes cognitive impairment – memory lapses, executive dysfunction, visual hallucinations, and mood disturbances like depression or apathy.Approximately 153,000 people in the UK live with PD. There is currently no cure for PDD, but patients can take medications called cholinesterase inhibitors to help manage symptoms. Existing treatments, such as cholinesterase inhibitors (e.g., rivastigmine, donepezil) and memantine, may provide some symptomatic relief but fail to halt or alter the underlying neurodegeneration.

Ambroxol: From cough syrup to neuroprotection

Ambroxol has been widely used in Europe for decades as a mucoactive agent – it helps clear phlegm and has an excellent safety profile. Its potential in neurodegenerative disease stems from its ability to enhance glucocerebrosidase (GCase) activity, a key enzyme encoded by the GBA1 gene. Reduced GCase activity leads to the build-up of alpha-synuclein, a hallmark of PD and PDD. By enhancing GCase, Ambroxol may promote the clearance of pathological proteins and reduce brain cell damage.

Key findings from the phase 2 trial

Researchers at Lawson Research Institute conducted a 12-month, randomized, placebo-controlled trial in 55 PDD patients, administering high-dose Ambroxol (525–1,050 mg/day). The major outcomes included:

Symptom stabilization: Placebo participants experienced significant worsening in neuropsychiatric measures, while those on Ambroxol remained stable.Brain injury marker (GFAP): Serum GFAP – a biomarker of neuronal damage – increased in the placebo group but remained stable with Ambroxol, implying neuroprotective action.Cognitive improvement in high-risk individuals: Patients harboring GBA1 risk variants exhibited noticeable cognitive gains.Safety and tolerance: Ambroxol was generally well-tolerated, with no serious adverse effects noted.One detailed report noted that high-dose Ambroxol recipients showed improved Montreal Cognitive Assessment (MoCA) scores by approximately 2 points, while placebo subjects declined.

Limitations and the way ahead

While findings are promising, they come from a small, single-center Phase 2 trial with limited diversity and may not be fully statistically conclusive. Certain dose‑response relationships remain unclear, and the subset of GBA1 carriers was small – about eight participants. Researchers are planning larger Phase 3 clinical trials in 2025 to specifically evaluate cognitive outcomes and determine optimal dosing strategies.

The parting thought

Ambroxol’s success could inspire wider interest in repurposing safe, existing medications for neurodegenerative disorders. It also supports the hypothesis that enhancing GCase activity may combat alpha-synuclein pathologies – a concept applicable to Parkinson’s, dementia with Lewy bodies, and potentially Gaucher disease.Moreover, this study draws attention to the value of targeted precision medicine – showing particular promise in patients with genetic risk factors (e.g., GBA1 variants). This could pave the way for more personalized neurotherapy approaches

What is your line of work?

All of my research is about the brain. I have two main lines of research in my lab. In one, we are developing ways to test how mechanical forces and drugs affect brain cells. We grow the brain cells in the lab and see how they behave under various conditions.

The other is research on an approach we call TrapKill, which uses a biomaterial that we are engineering with the hope to make therapies for brain cancer more effective.

My work applies engineering in medicine, and I have a joint appointment in the medicine and engineering schools here at the University of Galway and I work in Cúram, which is the Research Ireland Centre for Medical Devices.

TrapKill is a dramatic name – tell us more about it

TrapKill is a type of material called a hydrogel, which can be put into the body. We make it with three-dimensional channels in it that are designed to trap and compress cells.

The ultimate idea is that after a brain tumour, such as glioblastoma, is removed by surgery, the gel could be placed in the cavity to weaken the trapped cancer cells and make them more susceptible to radiation and drug treatments. I got funding for this project from the European Research Council.

You also grow ‘brains in a dish’ – can you explain?

We programme commercially available stem cells to grow into brains from the cortical region, particularly. Still, we can also combine them with other brain regions. I got national funding for this project through Research Ireland and Cúram.

What do you do with these groups of brain cells?

For some of them, we look at what happens when force is applied to them. This helps us to better understand how cells could respond to traumatic brain injury.

We also look at how the groups of cells respond to each other. For example, if we combine cells from different brain regions, we see faster development of star-shaped cells called astrocytes that carry out many functions in the brain.

How did you become interested in research?

Growing up in Medellín, Colombia, my parents were a huge inspiration. My father is a pharmaceutical chemist, and my mother is a retired bacteriologist. I loved visiting their labs as a child, and they inspired in me the persistence and rigour that are important for research. They still inspire me.

What was your journey to Galway?

I studied in Colombia, the United States, Italy and France, and I completed my PhD with Dr Manus Biggs in Galway. I then worked in the UK for a few years before returning to Cúram in 2022 and establishing my own lab here.

What keeps you going in your research?

I really love it. It’s hard work, the hours are long and you are always thinking about it, but I have a huge passion for research. I see so many people now who are living with cancer and brain diseases, and these are areas where we need research for even better treatments. This keeps me going.

What do you like to do outside of research?

I do reformer Pilates religiously, which keeps me strong and flexible. It’s a great antidote to all the sitting down and writing I do as part of my research. I love walking around and painting. I also have lovely plants that I take care of.

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