A research team at the UCL Queen Square Institute of Neurology has identified mutations in a gene called PSMF1 as a cause of a spectrum of severe neurological disorders, including early-onset Parkinson’s disease.

The findings, published in Nature Communications, are based on a study of 25 individuals from 18 families of diverse ethnic backgrounds and may help identify future therapies for Parkinson’s disease and neurodegeneration.

The PSMF1 gene produces a protein that helps regulate the proteasome – the system cells use to clear away damaged or misfolded proteins. This function is especially important in brain cells, where abnormal protein build-up can lead to neurodegenerative diseases.

The research, supported by the BRC’s Translational Neuroscience theme, found that mutations in PSMF1 disrupted the ability of cells to remove harmful proteins and produce energy efficiently. Researchers also found that loss of PSMF1 function led to movement problems and neurodegeneration.

The study reinforces the importance of involving people from diverse ethnic backgrounds in research, particularly in genetics research that has historically been globally dominated by work in Caucasian populations.

The discovery also complements related work on PSMF1 by collaborators at Rockefeller University in the USA.

 Parkinson’s disease is progressive and currently incurable, with up to 15% of cases linked to changes in single genes, particularly in early-onset forms of the condition. Studying these inherited forms of disease has helped scientists uncover biological pathways that are also relevant to more common forms of Parkinson’s disease and has informed the development of several treatments currently being tested in clinical trials.

First author of the paper Dr Francesca Magrinelli, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, said: “Parkinson’s disease affects around 170,000 people in the UK, with a new diagnosis occurring every 20 minutes. Globally, the number of cases is projected to exceed 25 million by 2050. So, there is a huge need to understand the disease and related conditions, and to find new therapies.

 “More work is needed first – but ultimately in future we want to investigate in clinical trials whether gene therapies that restore PSMF1 function could form the basis of new treatments for neurodegenerative diseases.”

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