Understanding the causes and progression of Parkinson's disease
Researchers at the RVC, UCL, Oxford and Cambridge are undertaking pioneering study into the causes and progression of Parkinson’s disease, supported by a $7 million grant from the Aligning Science Across Parkinson’s (ASAP) initiative.
Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s. It is a progressive disease of brain degeneration that occurs when brain cells that make dopamine, a chemical that coordinates movement, either stop working or die. This causes people with Parkinson’s to develop slowness, tremors, stiffness, and walking and balance problems. The disease can also lead to problems with cognition, mood, and sleep.
Parkinson’s affects over 130,000 people in the UK and approximately 10 million worldwide. The currently available treatments act only to alleviate symptoms, but not slow progression of the disease. Levodopa is a drug that replaces dopamine, the main chemical produced by the neurons that Parkinson’s disease attacks. However, its effect tends to wear off after four to seven years and can cause side effects. Other drug treatments try to mimic the action of dopamine, protect it from breakdown or preserve movement ability through other molecular pathways. For some people with Parkinson’s disease, surgically implanted electrodes have relieved symptoms.
Because science doesn’t yet have adequate understanding of how Parkinson’s disease starts and progresses, the challenge of developing a disease-modifying drug is significant.
The ASAP Collaborative Research Network is a global consortium of researchers bringing together investigators across multiple disciplines, institutions, career stages, and geographies seeking to tackle key knowledge gaps in the basic mechanisms that contribute to Parkinson’s development and progression. The ASAP CRN fosters deep collaboration within and across teams, with a mandate for open science and open access publication.
The ASAP grant will enable the RVC and UCL researchers to explore the possibilities of future prevention and treatment of the condition. The researchers at the RVC, led by Dr Patrick Lewis, Professor of Neuroscience, have been awarded $659,000 from ASAP to use cellular and biochemical approaches to investigate the role of the LRRK2 and other genes in the mechanisms that underlie the progressive decline seen in Parkinson’s. Mutations in the LRRK2 gene are the most common genetic cause of Parkinson’s, making it a priority drug target for the disease. However, the molecular details of how this gene can influence the progression of neurodegeneration in Parkinson’s have not yet been fully explored.
The RVC team are working closely with geneticists, basic biologists, clinicians and pathologists at UCL, Oxford and Cambridge to identify and characterise new genes involved in progression – with the ultimate goal of finding ways to slow down or even halt the progression of Parkinson’s.
At present there are no drugs available for Parkinson’s that act to slow down or halt the progression of the disease. Our aim with this project is to provide the foundations for new therapies that can alleviate the decline experienced by people living with Parkinson’s, providing treatments at the earliest stages of the disease so that they can live their lives to the full.
|Modelling the functional genomics of Parkinson's disease in Caenorhabditis elegans: LRRK2 and beyond||Bioscience Reports||2021|
|From structure to ætiology – a new window on the biology of Leucine Rich Repeat Kinase 2 and Parkinson’s disease||Biochemical Journal||2021|
|Integrating protein networks and machine learning for disease stratification in the Hereditary Spastic Paraplegias||iScience||2021|
|An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of a-synuclein||Cell Reports||2021|
|Preclinical modelling of chronic inhibition of the Parkinson’s disease associated kinase LRRK2 reveals altered function of the endolysosomal system in vivo||Molecular Neurodegeneration||2021|
|Identification of Candidate Parkinson Disease Genes by Integrating Genome-Wide Association Study, Expression, and Epigenetic Data Sets||JAMA Neurology||2021|
|Vesicle trafficking and pathways to neurodegeneration||Molecular Neurodegeneration||2021|