Right drug, right patient, right time for rare neurological disease
Motor Neurone Disease - from the ice-bucket challenge to the recent diagnosis of journalist Charlie Bird, many people are aware of this progressive degenerative disease, where the body’s nervous system loses function over time.
For decades, scientists and doctors have grappled with how to help patients with this rare condition, particularly because it can arise and affect people in different ways. Now a Science Foundation Ireland-funded project wants to enable a smarter approach to understanding and ultimately treating Motor Neurone Disease, or ALS as it is also known.
Enter Precision ALS, a Europe-wide consortium that seeks to gather, analyse and use many different types of information about ALS to improve treatments and quality of life for patients.
Led by clinician scientist and 2022 SFI Researcher of the Year Professor Orla Hardiman, the consortium is taking a broad view of how the disease starts and develops in patients; of how we can use many different approaches or ‘modalities’ from genetic analysis to brain imaging to diagnose and monitor the disease; and of course looking for new ways to support and treat individual patients on their journey with the condition.
One of the core issues with ALS is how differently it can appear in patients, making it more difficult to spot useful patterns, explains Professor Hardiman, who is a Consultant Neurologist at Beaumont Hospital in Dublin and Professor of Neurology at Trinity College Dublin.
“Not only is ALS rare, there are probably multiple different pathways to the disease, for example we know that many different genes can operate in different ways as the disease develops,” she explains. “So most likely it is a spectrum condition that can be caused by a variety of different mechanisms in the body.”
The Precision ALS project wants to capture information about the disease in a way that helps find the most suitable treatment plan for a particular patient at a particular stage in their ALS, says Professor Hardiman. “If we want to either target the underlying mechanism or to manage the progression of the symptoms, we need to have a better handle on how to characterise the disease in a more sophisticated manner that we do at the moment,” she says.
“So in this project we are looking to bring together the clinical information, the kind of changes that I can detect as a trained neurologist, and also harness the power of other technologies in which we have made strides in research over the years, such as changes in the expression of particular genes or levels of particular proteins, and insights we have from advanced imaging of the brain, and exciting developments in how we can measure disease associated differences in neuroelectric networks by analysing brain wave using complex mathematics.”
Professor Hardiman has blazed an international trail in ALS research for almost three decades, including building a registry or bank of information and samples from patients and families in Ireland with the condition. She and colleagues have made important discoveries such as the involvement of the ANG gene in ALS and novel insights into biological overlaps between ALS and other neuropsychiatric conditions such as schizophrenia.
Through the Precision ALS project, this kind of information can be integrated into an international framework alongside other discoveries about the disease - including future discoveries - to identify individuals or groups of patients who could benefit from specific treatments, or who could access and trial emerging treatments. The result, explains Professor Hardiman, will be greater than the sum of its parts.
“It is really exploring and building out on some of the discoveries we have made over the years and then trying to Integrate those discoveries into something that is useful in the longer term, and that can be then integrated into a system that is self-perpetuating,” she says. “We want to make it easier to capture and use this information across Europe, rather than having humans - research assistants and nurses - wearing out foot leather and time gathering and cataloguing all this information. The Precision-ALS framework will enable us to access and use this information more efficiently.”
One of the keys to Precision-ALS is having people with many different backgrounds working on the problem together. Researchers from the SFI FutureNeuro Centre are focusing on the clinical and molecular presentations of the disease, while researchers at the SFI Adapt Centre are exploring how to best capture, share and analyse the information using artificial intelligence. The researchers will work together with a number of companies including Biogen, Novartis, Takeda, IQVIA, Roche and Accenture, and in partnership with TRICALS, an independent consortium of ALS experts, patients and patient advocacy groups across Europe.
Bringing the €10-million project together is a challenge, notes Professor Hardiman. “The technological difficulties and pitfalls are not trivial, there are many moving parts to this,” she says. “It has not been done before in this way and it is difficult, but it will enable us to translate clinical and research findings into something much more meaningful for patients.”
"The hope is that it will help to identify the right patient for the right drug or treatment for the right time, while also supporting the search for new drugs and treatments into the future."