National Brain Awareness Week: Let’s get moving on Parkinson’s disease
Posted on: 15 March 2021
As part of National Brain Awareness Week (March 15-21st 2021), we chatted with Andrew Harkin, Professor in Pharmacology, School of Pharmacy & Pharmaceutical Sciences and Deputy director, Trinity College Institute of Neuroscience, to discover more about his research on Parkinson’s disease.
Let’s get moving on Parkinson’s disease; transforming research and discovering promising directions for new treatments.
Tell us about your research?
Andrew Harkin (AH): Parkinson’s disease is a progressive brain degenerative condition which occurs when brain cells that make dopamine, a chemical that helps us to co-ordinate our movements, lose function and die. There is no cure. The drugs currently used to treat the disease are still based on concepts that are decades old. Why these cells are lost is a mystery but progressive scientific research carried out in laboratories around the world is presenting us with a promising lead.
A protein, alpha synuclein, forms fine threads and accumulates in cells in deposits that are called Lewy bodies. These trigger inflammatory-like responses in the brain and cause cell death. Development of treatments is challenging on account of the need to get a therapeutic into the brain, targeting where synuclein is aggregating and driving inflammation, whilst minimising potential side effects in the body.
With a better understanding of synuclein and its underlying role in disease, a next step involves finding new drugs, or repurposing old ones, that target synuclein or synuclein-related effects, to treat, slow down, or even prevent the disease.
My research in Trinity approaches this challenge by adopting drug treatment strategies in the laboratory, to reduce synuclein burden, block synuclein-related brain inflammation and protect dopamine cells from synuclein-related loss. This has required advanced tools used to drive the expression of synuclein in cells and in clinically relevant animal models. From this base, we are fascinated by what we are discovering.
How many people are affected by Parkinson’s in Ireland?
AH: There are approximately 12,000 people living with Parkinson’s disease in Ireland and the disease affects more than 6 million people worldwide. It affects somewhere between one or two persons out of 1,000 and this rises to one out of every 100 people aged 80 and over. Abnormal deposits of alpha-synuclein are also linked to other neurodegenerative diseases including Lewy body dementia, the second most common form of dementia next to Alzheimer’s disease, which in addition to producing problems with movement, is associated with problems thinking, and with changes in behaviour and mood.
Did any of your research findings surprise you?
AH: Noradrenaline is a chemical messenger which is made in the brain and is required for a range of different activities such as our response to stress and threats, paying attention and other cognitive behaviours, among others. Our research has uncovered a lesser known function of noradrenaline which is an anti-inflammatory action in the brain which plays an important role in maintaining the brain in a healthy state. Noradrenaline is depleted in brain degenerative diseases which contributes to disease progression.
Consequently, therapeutics aimed at restoring noradrenaline have potential in preventing disease progression. To advance this research toward a new treatment for Parkinson’s, and potentially other brain degenerative diseases, consideration of how drugs access and target affected brain areas safely and effectively is paramount. Development of a neuroprotective medicine which serves to promote or mimic noradrenaline to reduce inflammation in a targeted manner where synuclein deposition and aggregation occurs, is a highly promising prospect.
Who will benefit from this research and how?
AH: This profoundly important research is paying important dividends for everyone. With advances in technology, the cascade of events that are causing disease are being revealed and unlocked at nanoscale. These findings are providing new targets for the development of drug therapies. For brain degenerative diseases, baseline costs run into hundreds of millions of euro in Ireland with the costs for society estimated to be at least ten times higher. As a country , with a growing aging population, we need to urgently tackle the challenge of age-related brain degenerative diseases.
Is your research unique?
AH: We are very fortunate in Trinity to be based within an interdisciplinary research environment that includes Trinity College Institute of Neuroscience (TCIN) and the Global Brain Health Institute (GBHI), both internationally recognised research centres, which facilitate collaborative research initiatives on understanding brain function in healthy and diseased states.
While Ireland already has a global reputation in the quality of pharmaceutical products manufactured here, building a research and development culture is critical. In this respect we are fortunate to be in partnership with enterprise with backing from the Irish Research Council, who are investing in and supporting our research. Furthermore, we are excited about a new collaborative direction with the School of Pharmacy and the Pharmaceutical Sciences in Trinity College who have expertise in nanomedicine-based approaches and the application of the tools of nanotechnology to deliver useful cargo to the brain. We are in a new era of research endeavour, which involves the use of nanoscale materials to assemble biocompatible nanoparticles, for molecular and cellular targeting of synuclein related inflammation and delivery of anti-inflammatory drugs to protect vulnerable dopamine brain cells.
The ultimate ambition is to contribute to development of next generation drugs. This may be realised sooner rather than later, as we are seeing promising efficacy in the laboratory with some drugs, already currently approved and in clinical use for entirely unrelated diseases. Our mission will be to translate these results for the benefit of patients, by way of a constructive and collective effort to make new, safe and effective therapeutics for treating synuclein related brain diseases, a reality.