The Brain Research UK Miriam Marks Research Fellowship scheme was established in 2020 in partnership with UCL Queen Square Institute of Neurology. The scheme is funded by the Miriam Marks Endowment Fund, which was established by the family of Mrs Miriam Marks in 1971 to support research into brain degeneration.
This award to Professor Antonella Spinazzola, one of two Fellowships awarded in 2020, will support her research into Parkinson’s disease, a progressive, degenerative neurological condition affecting around 145,000 people in the UK.
Professor Antonella Spinazzola is a neurologist with over 20 years’ experience studying the role of mitochondria in human diseases, in both clinical and laboratory settings.
As a junior doctor, working with people with rare mitochondrial diseases - often with profound neurological involvement - she became frustrated by the frequent inability to 'give a name' to the specific disorder and, even more, by the lack of treatment options. She therefore embarked upon a research career, determined to advance gene discoveries and mechanistic understanding of the pathologies of these diseases, with the view that this was the best route to the development of effective treatments.
During her career she has made major contributions to mitochondrial biology, culminating in the identification of potential treatments that are currently being tested in disease models, and in a human safety and efficacy trial, thus coming full circle. Her studies of rare mitochondrial diseases have also revealed fundamental aspects of cell and organ biology that have far-reaching implications for neurodegenerative conditions, in particular Parkinson’s disease.
Parkinson’s disease (PD) is a progressive and devastating neurological condition, affecting around 145,00 people in the UK. It is caused by the loss of cells (neurons) in the brain, especially those that produce dopamine, a chemical that carries signals between neurons, enabling us to perform smooth, coordinated movements.
The lack of dopamine gives rise to the three main symptoms of PD, namely tremor (shaking), slowness of movement, and rigidity (muscle stiffness). These symptoms usually begin gradually and get worse over time, as the disease progresses. Those affected may also have difficulty walking and talking, and may suffer mental and behavioural changes, sleep problems, depression, memory problems, and fatigue.
Whilst there are some treatments that can relieve the symptoms of PD, there are no treatments that can slow or delay progression of the disease. These kinds of neuroprotective treatments are the major unmet need in PD, yet their development is hampered by critical gaps in our knowledge of the underlying molecular mechanisms of the disease.
Mitochondria are vital components of human cells, found in all cells except red blood cells. They are powerhouses that convert food and oxygen into energy to support cell function. Whilst this can cause any organ to fail, the brain's high energy demand makes it especially vulnerable to mitochondrial dysfunction.
Professor Spinazzola’s research has focused on the small circles of DNA in the mitochondria that produce proteins that are essential for energy production. Recently, her studies have led to the discovery that multiple processes and pathways impaired in PD affect - and are affected by - changes in mitochondrial DNA metabolism. Her findings unify many earlier observations in the field of PD, and suggest that mitochondrial DNA metabolism is at the centre of a network of organelle interactions, perturbation of which can lead to PD.
With the support provided by this Fellowship, Professor Spinazzola will build on these recent discoveries to further advance our understanding of the role of mitochondrial DNA metabolism in brain disease and test new therapeutic approaches for PD.
Parkinson’s disease is a debilitating condition that limits the ability of those affected to live an active, independent life. Symptoms get progressively worse and there is no treatment that can slow this decline. Finding a treatment that could halt progression of the disease would be life-changing for those affected.
Professor Spinazzola’s project aims to address this unmet need by identifying novel targets in disease-relevant pathways, and to use this knowledge to develop therapeutic interventions.
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