Primary Lateral Sclerosis (PLS) is a type of MND that progress slowly over many years. It is estimated that around 3 in 100 people diagnosed with MND have PLS and is therefore considered a rare form of the disease. PLS commonly begins with symptoms affecting the movement and communication. People with PLS develop muscle stiffness, difficulties with walking and balance, and slurred speech.
Just like other forms of MND, diagnosing PLS takes time as it relies on doctors ruling out other diseases that may cause similar symptoms before a diagnosis is given. There are currently no effective treatments and what causes the disease remains a bit of a mystery.
PLS shares some characteristics with the most common form of MND, amyotrophic lateral sclerosis (ALS). Scientists who are experts in ALS, recognising key similarities and differences between the two conditions, are advancing our understanding on PLS. Researchers and clinicians around the world are working together to improve diagnosis, develop new effective treatments, and better understand the underlying causes of the disease.
Research into PLS was brought into the spotlight at the 36th International Symposium on ALS/MND in San Diego. In previous years, PLS has been discussed in separate meetings held before the main event. This year, for the first time ever, PLS had its own dedicated session as part of the Symposium programme, highlighting growing recognition of the condition and the urgent need for further research.
The PLS Session
The session was co-chaired by Dr. Sabrina Paganoni and Dr. Angela Genge, both of whom opened by expressing their excitement and gratitude for this milestone and for the growing recognition of PLS within the broader ALS/MND research field.
We are deeply grateful to the MND Association for including Primary Lateral Sclerosis in the main track of the International Symposium on ALS/MND. As a rare form of MND, PLS has historically been underrepresented, and this important step will help catalyze progress in both care and research. We look forward to working together to foster global, collaborative initiatives that advance understanding and improve outcomes for people living with PLS.- Dr Sabrina Paganoni, co-chair of the PLS Committee and the PLS registry of the Network of Excellence for ALS (NEALS).
The session began with Dr. Hiroshi Mitsumoto presenting an overview of the remarkable growth in PLS research. He shared data showing how scientific interest in PLS has accelerated in recent years and expressed strong optimism about the future of PLS research. Following this, presentations from five experts in the field covered major advances in understanding upper motor neuron degeneration, disease variability, and clinical trial readiness.
Dr Hande Ozdinler shared advances in understanding the damage to a type of motor neuron called upper motor neurons, which help the brain control body movement and is the main type of motor neuron that breaks down in PLS. She discussed how her team have found unique changes in genes and proteins that happen in upper motor neurons in PLS and these changes can help us to understand what is happening in upper motor neurons in the disease. This information could lead to further research and the development of possible treatments for upper motor neuron damage and PLS.
Dr Anita Jain built on this presentation to discuss research looking into gene and protein changes seen in upper motor neurons. Her team used post mortem brain tissue to identify and compare changes that happen in upper motor neurons and lower motor neurons in MND. She discussed how they found some gene changes that may play a role in the development of upper motor neuron damage. This study is ongoing and could reveal biological similarities and differences involved in upper motor neuron and lower motor neuron damage in MND, which may help to explain why people with MND experience different symptoms and progression.
Dr Michael Benatar highlighted an ongoing study looking at 60 people with PLS with the aim of identifying new disease specific biomarkers and understanding more about the links between gene changes, environmental factors and symptoms. Every 6 months, the participants complete questionnaires, give information about their symptoms and have biological samples collected.Part of this long-term study is investigating clinical trial design. It is looking into different ways to measure changes in clinical symptoms in people with PLS and may reveal which method might be the best way to detect changes in clinical trials. It could also indicate how long the trials might need to be to accurately measure whether a treatment is having an effect on symptoms.
Dr. Michael van Es discussed results from a long-term study following people thought to have PLS. The study participants were assessed every 9 months for up to 3 years and then further assessed at care centres for around 10 years. Over time, 12% of those thought to have PLS developed ALS and 7 people were found to have another motor neuron disease called HSP. One of the conclusions from this study was that people who meet PLS diagnostic criteria might go on to develop ALS and need long term assessments to make sure they have received an accurate diagnosis. It also highlighted the need for better ways of diagnosing PLS so that clinicians can be sure that someone does have PLS rather than another type of MND.
Dr. Ikjae Lee also presented his study looking into PLS diagnosis, ways to measure clinical changes during the disease and identifying biomarkers. He shared data from an ongoing long term study following 76 people thought to have PLS, which is running at 30 sites across USA and Canada for 2 years. This study also looked at different ways to detect changes in clinical symptoms for people with PLS and which might be the best method to use in clinical trials. It identified two outcome measures that might be useful for clinical trials and found that including people who are early in disease stages might reduce the number of people needed to take part in trials to show treatment effects. He suggested that monitoring levels of a biomarker called Neurofilament Light Chain in PLS might be useful in predicting disease progression and could indicate if someone may go on to develop ALS. This research could help to determine how clinical trials in PLS are designed and lead to the identification of biological markers of disease in the future.
The speakers then each shared an idea for collaboration or future research in PLS that could lead to even more advances in the field.
The session concluded with an announcement of two new PLS abstract awards honouring the legacy of Thurza Campbell and the Marren Family. These will be presented for the first time at the 37th International Symposium on ALS/MND later this year.
It was beautiful to see the PLS community together: so engaged and so motivated. Honoring our patients through the PLS abstract awards made the moment especially meaningful.- Dr Erica Scirocco, Post Doctoral Research Fellow at the Sean M. Healey & AMG Center for ALS, Massachusetts General Hospital (MGH).
We’re delighted to bring these research communities closer together through the International Symposium. PLS and ALS share many common features, not only in symptoms and clinical management, but also in the underlying pathology and disease processes. This means that new discoveries in one form of MND are likely to also advance our knowledge of other forms as well, accelerating the identification and development of potential new treatments across the board. – Dr Brian Dickie, Chief Scientist, MND Association.
Planning is already underway for the PLS session at the 37th International Symposium on ALS/MND in Amsterdam later this year, and we look forward to hearing more global advances in PLS research and care there.
We would like to thank Dr Sabrina Paganoni, Dr Erica Scirocco and Elizabeth Eagles Blue for their contributions to this blog.
