The rapidly evolving field of precision medicine and how it is reshaping the understanding and treatment of motor neurone disease (MND) is explored in a recent review led by researchers in Western Australia as part of an international collaboration including Kings College London.
Published in the high-impact journal Molecular Neurodegeneration, the paper addresses advances in understanding the complex genetic architecture of amyotrophic lateral sclerosis (ALS), the most common form of MND, leading to progressive muscle weakness and paralysis.
The paper emphasises the importance of understanding population genetics and genetic testing when considering patient selection for clinical studies.
Additionally, the review discusses advances in long-read whole genome sequencing and how it can help streamline genetic testing, and when combined with ‘omics’ data and machine learning, these tools can help identify specific patient sub-groups and enhance preclinical drug development.
Lead author Dr Frances (Frankie) Theunissen is a FightMND Early Career Research Fellow at The University of Notre Dame and the MND Genetics and Therapeutics Research group based at the Perron Institute, the Personalised Medicine Centre (PMC) Murdoch University, and an affiliate of Kings College London.
“Until recently, treatments could only slow disease progression by less than three months in some patients with ALS, but new genetic and molecular tools are now revealing ways to target the disease,” Dr Theunissen said.
“Currently there are only three approved disease modifying therapies to treat amyotrophic lateral sclerosis (ALS). With only three treatments contributing to varying levels of disease modification, there is considerable focus on improving both the efficacy and number of available treatment options to modify disease progression.
“Our paper highlights the success of the first gene-targeted therapy for ALS, approved for use by the United States Food and Drug Administration, the European Medicines Agency, and the Medicines and Healthcare products Regulatory Agency in the UK and other regulatory authorities.
“This antisense (molecular genetic) therapy works by silencing a faulty form of the SOD1 gene that is commonly associated with ALS.
“Precision medicine means giving the right drug to the right patient at the right time. With the emergence of antisense oligonucleotide technologies, additional gene targeted therapies will soon enter the market for ALS.
“Our research looks ahead to how precision medicine principles can be applied to other genetic forms of ALS, and even to so-called ‘sporadic’ cases, as new technologies help us understand the genetic and molecular differences that make each person’s disease unique.”
“For a young and growing research group, publication of this review in a leading journal recognises the calibre of the work being carried out,” said co senior author Professor Anthony Akkari, Head of the MND Genetics and Therapeutics Research group and Director of the Personalised Medicine Centre.
“It also reinforces the ethical importance of ensuring that emerging treatments are available to all, regardless of geography or income — a message close to our hearts at the Perron Institute and the Personalised Medicine Centre.
“This publication marks a significant milestone for our team and for our mission to advance next-generation genetic therapies for ALS. With collaboration, innovation and integrity, we are building new pathways for discovery that bring real hope to patients and families affected by this devastating disease.”
Co senior author of the paper is Dr Masha Strømme (PMC), and other authors are Dr Loren Flynn (PMC and Perron Institute), Professor Alfredo Iacoangeli (Kings College London), Dr Ahmad Al Khleifat (Kings College London and Perron Institute), Professor Ammar Al‑Chalabi (Kings College London and Perron Institute), and Dr James Giordano (Georgetown University Medical Centre, Washington, DC, USA).
Photo of Dr Frances Theunissen courtesy The University of Notre Dame