Research targets root cause of Parkinson’s disease as cases set to rise

A government-funded University of Malta research project called Minds is investigating the role of mitochondria in neurodegenerative diseases, with a focus on Parkinson’s disease.

The Minds project is studying mitochondria (cell energy structures) and their role in neurodegeneration. The aim is to have a better understanding of the loss of brain cells in conditions like Parkinson’s disease. The project is being funded by the Secretariat for Youth, Research and Innovation, under the initiative of Parliamentary Secretary Keith Azzopardi Tanti

The Malta Independent on Sunday spoke to Professor Neville Vassallo, the lead researcher behind the project and lecturer at the Department of Physiology and Biochemistry of the University of Malta. He explained that recent scientific literature and health data indicate that Parkinson’s disease is the fastest-growing neurological condition globally, outpacing dementia and stroke. Cases in Europe are projected to increase by 50% by 2050, according to a study published last year in the British Medical Journal. Over 1 million people in Europe currently live with Parkinson’s. In Malta, there are about 3,000 cases.

Parkinson’s disease is in fact the second most common neurodegenerative disease, after Alzheimer’s. It involves the progressive death of brain cells related to movement, Vassallo explained. It is more common in men and typically affects older adults, but it can also occur in younger people in their 30s and 40s, often due to genetic factors.

Parkinson’s is a movement disorder causing slowness of movement and difficulty initiating actions such as standing and walking. It also causes muscle stiffness, tremors (especially at rest), reduced facial expression and small handwriting. The disease also significantly increases the risk of falls, with many patients ending up in hospital. Moreover, other disorders may coincide with Parkinson’s, such as sleep disorders, depression, and even dementia.

Vassallo highlighted the major misconception that Parkinson’s disease is just a disease of the elderly, or a normal part of ageing. It is a serious neurological condition, and not part of the natural ageing process. Moreover, the public may often think that Parkinson’s is just a tremor. In reality, it involves considerable movement difficulties that go beyond a mere tremor, with the loss of independence for tasks such as dressing or eating, and the need for long-term care and support. It is also a progressive condition that worsens over time.

Vassallo said that the disease is driven by a loss of dopamine, which is a crucial brain chemical. This happens because dopamine-producing cells in the brain progressively die. Symptoms typically appear after more than half of these cells are lost. There are existing pharmacological treatments, such as Sinemet, which replaces dopamine temporarily. But this only improves symptoms and does not stop the disease’s inexorable progression. The effectiveness of Sinemet, for instance, typically declines after 5-10 years.

The same goes for surgical treatments such as Deep Brain Stimulation (DBS), whereby symptoms improve, but the dopamine cells continue depleting. Moreover, DBS is only suitable for selected patients, often younger ones, and is not widely applicable. Therefore, while current treatments can improve symptoms, they do not stop the fundamental drivers of the disease.

The Minds project aims to change that, laying the scientific foundations for future therapies that could slow, or even halt, Parkinson’s. Vassallo explained that research will be conducted in the laboratory, not on patients, using lab-grown brain cells similar to dopamine neurons. The project will focus on mitochondria – the cell’s energy “power stations”. These are especially abundant in dopamine-producing neurons. The key idea is that if the mitochondria fail, the cell loses energy, and it dies. Researchers will thus isolate mitochondria and study how, and why, they become damaged.

The project also aims to find new strategies to protect mitochondria, keeping brain cells healthy. Healthy mitochondria, Vassallo explained, means healthy cells, and thus slower disease progression. Therefore, the focus is not just on understanding the disease, but on preventing cell death.

The research will be conducted in partnership with the Max Planck Institute for Multidisciplinary Sciences in Germany, which is one of the world’s top research institutions, as well as the Centre for Neurodegenerative Disease Research, also in Germany. This will give the project’s researchers access to thousands of chemical compounds to test for potential treatments.

The researchers aim to identify compounds that could become future drugs. The approach is described by Vassallo as “bench to bedside”, meaning from lab research to eventual patient treatment. That being said, no cure or drug is expected to result immediately from this three-year project. Drug-development, Vassallo explained, often takes around 15 years of animal studies and clinical trials. This project is simply a first step intended to generate knowledge and potentially lead to future, larger research projects.

“The medicines we will use in the future are the ones we are discovering through research today,” Vassallo said.

Vassallo stressed that research must “push boundaries” and explore new niches. The project’s focus on mitochondria aims to be innovative and not previously explored in the same way. What makes Minds different is that the project aims for “disease-modifying treatment”. This targets why brain cells die, not just the symptoms of the disease. The goal is to slow or stop disease progression, and to complement – not replace – existing therapies. While the research will not deliver an immediate cure, it represents a crucial step in understanding Parkinson’s disease and building the foundations for future treatments that could one day change patients’ lives.

In addition to its primary scientific objectives, the project will also enable training of highly-skilled researchers and build expertise in advanced lab techniques. Most of the experimental work is done by a small, specialised research team. Unfortunately, the risk exists that skilled researchers may leave Malta due to a lack of research-driven industries and jobs.

Talking more generally about university-based research, Vassallo said that such research, at a significant scale, could support a knowledge-based economy. He cited a 2024 study by the London School of Economics which revealed that for every £1 of public money invested in universities, £14 of economic benefit are generated in return. Thus, university research can act as a driver of economic growth, through initiatives like startups and research grants.

“Therefore, research like the Minds project actually leads to higher added value,” Vassallo concluded. 

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