ALS researchers from around the world continue to build upon existing work and make new discoveries in the hopes of realizing a world free of ALS. In the October 2024 Research Update, explore new insights into promising brain-computer interface technology, understanding the diversity of people living with ALS, promising new therapeutic areas, and more. 

We have developed a research glossary that contains a list of scientific and medical terms and definitions relevant to ALS. This glossary was created to support knowledge-sharing by helping to provide clarity around terminology that may be unfamiliar to our readers. Click here to download a copy.  

 

Mind Over Chatter: brain-computer interface shows promise as an assistive communication device for ALS 

A recent study by University of California, Davis, investigated the use of brain-computer interfaces (BCIs) in facilitating communication for a 45-year-old man living with ALS. Five years after the onset of the disease, the participant, affected by severe paralysis and difficulty speaking, underwent a small surgical procedure for the implantation of four microelectrode arrays in his left ventral precentral gyrus – a part of the brain responsible for speech production.

The technology, explained simply, translates brain activity into text. Researchers were able to decode the participant’s brain signals as he tried to form words. These decoded words were then displayed on a computer screen and vocalized through a text-to-text speech system.

Generally, the challenge for BCIs has been the high level of training required and the limitations in accuracy and speed. The results of this study show promise in addressing those limitations: the calibration process, which involves recording brain signals while the participant attempted to speak, took just 30 minutes. Additionally, on the first day of testing, twenty-five days after the surgery, the technology achieved a 99.6% accuracy in translating his brain activity into text, although with a limited vocabulary of 50 words. On the second day of testing, the device reached 90.2% accuracy with a much larger vocabulary of 125,000 words. Over the next 8.4 months, the system maintained an accuracy of 97.5%, allowing the participant to engage in conversations at a speed of 32 words per minute. You can see a video of the participating communicating with his family here.

Although promising, the technology still needs continued research and refinement, and it may still be years away before BCIs can become a standard method for restoring communication, in comparison to traditional assistive technologies that use eye movements or muscle control. Another potential limitation of the technology is longevity, as it has not been extensively examined in people living with ALS. Another recent study indicated that the accuracy of BCIs may decline over time as the disease progresses.  

Other studies currently investigating brain-computer interfaces include BrainGate2 and the PRIME study by Neuralink, which is currently seeking participants. You can learn more about participation here 

If you are interested in learning more about brain-computer interface technology, watch a talk from ALS Canada’s 3rd Virtual Research Forum with Dr. Nick Ramsey.  

 

New efforts toward understanding ALS diversity: Project Mosaic & ALL ALS 

ALS is a heterogenous disease, meaning every person living with ALS will be affected differently. These differences can affect symptom progression and management, individual responses to potential treatments, and clinical trial participation. To properly discover effective therapeutics for ALS, these gaps in our understanding of the disease need to be tackled. 

Toward improving clinical trials and drug development to better address the diversity of people living with ALS, Project Mosaic was formed by a consortium of ALS nonprofits and industry stakeholders. Most commonly in the laboratory, researchers will study ALS in genetic models of the disease. But since ALS cases without an apparent gene variant represent over 75% of cases, potential therapeutics tested in genetic models in the lab often fail to replicate the same promising results in clinical trials.

Project Mosaic aims to evaluate and validate the best representative model to study ALS cases with no known genetic cause, using induced pluripotent stem cells (iPSC). These cells make it possible to create essentially any cell type in the body using any other as a starting point. This means that researchers can take skin or blood samples from people living with ALS and convert them into motor neurons to be studied in the lab. The validation and distribution of an ALS model that better reflects the disease’s heterogeneity will hopefully have a significant impact on improved drug development and clinical trial validation.   

Additionally, the National Institutes of Health (NIH) launched the “Access for ALL in ALS” (ALL ALS) consortium in the United States. ALL ALS will be a part of the Accelerating Medicines Partnership in Amyotrophic Lateral Sclerosis (AMP® ALS), that will bring together multiple research institutions across the US to collect and store data from people living with ALS and from those at risk of developing the disease (ALS gene variant carriers). By collecting important information about the diversity of people living with ALS, the initiative can bring us closer to personalized drug development and identify reliable disease biomarkers, to better track disease progression and potentially aid in earlier diagnosis. 

ALL ALS will emphasize inclusion of diverse geographically, ethnoculturally, and socioeconomically misrepresented groups in research. The collected data will include clinical and genetic information; family, medical, and environmental history; biofluids and symptom progression; and other patient reported measures such as quality of life and emotional aspects. All data will be made available to researchers to support innovative approaches in understanding ALS and new therapeutic avenues.   

ALS Canada is committed to Canada’s contribution to global ALS research. We are excited to announce our partnership on AMP® ALS, contributing over $125,000 to the initiative over the next five years.

“AMP® ALS is the kind of collaborative initiative we have needed for a long time. There have been many amazing, independent ALS research initiatives around the world but their true power will be revealed when we bring them all together. ALS Canada is proud to partner with all of these great organizations, sharing the common goal of accelerating our understanding and treatment of ALS. Together, through AMP® ALS, we change the world for this disease.” – David Taylor, VP, Research & Strategic Partnerships

Additionally, ALS Canada have also initiated discussions to integrate data from CAPTURE ALS into AMP® ALS. CAPTURE ALS is a Canadian platform also uniting people living with ALS, physicians, and researchers by collecting multiple measures of people living with ALS. Data collected from CAPTURE ALS can provide us with the opportunity to massively accelerate the development of effective treatments for the disease.

Read more about CAPTURE ALS and how to participate in the study.  

 

 

Shining a light on neuroinflammation: how targeting these star cells may have a protective effect in ALS 

ALS causes the degeneration and death of the nerve cells responsible for voluntary muscle movement, called motor neurons. This is why, over time, people with ALS lose the ability to walk, talk, and eventually breathe. Researchers know that the disease can also affect supportive cells to motor neurons, influencing their overall environment and leading to chronic inflammation in the nervous system.  

In a recent scientific study led by Prof. Ludo Van Den Bosch’s team (VIB-KU Leuven Center for Brain & Disease Research), neuroinflammation is studied in more depth as a potential key therapeutic area.  A specific type of star-shaped support cells in the nervous system, called astrocytes, are known to be heavily involved in a neuroinflammation response in ALS that some scientists believe is caused by an altered response to interferons. Interferons are proteins produced by the immune system that can increase inflammation in the body. 

With the goal of reducing neuroinflammation, researchers investigated an enzyme called EGLN2, that plays a critical role in regulating inflammation and energy at the cellular level. By using animal models of ALS such as zebrafish and mice, as well as astrocytes made from people living with ALS, scientists found that reducing EGLN2 levels can turn off this inflammatory switch in astrocytes by normalizing interferon response. This had a neuroprotective effect in the ALS models and reduced motor neuron degeneration.  

The study reinforces the idea that EGLN2 regulation could be an effective therapeutic strategy for ALS – by reducing inflammation linked to astrocytes, leading to a healthier environment for motor neurons, and potentially slowing disease progression. Additionally, the authors emphasize the importance of further studies to better understand these supportive cells and what role they play in neuroinflammation and disease.  

 

Brain drain: what role does the glymphatic system play in ALS? 

One of the most recent areas of research focus in ALS involves the glymphatic system – the brain’s  “drainage system”. This system works mainly while we are sleeping, clearing out toxins and harmful proteins. A hallmark of ALS is the accumulation of misfolded proteins in cells, which may contribute to degeneration in motor neurons, the cells in the brain responsible for voluntary movement. Researchers are aiming to uncover what role the glymphatic system may play in ALS through clearing this protein accumulation, and whether this could potentially be a new therapeutic target.  

In a recent study, a team co-led by Dr. Minh Dang Nguyen, Dr. Richard Frayne & Dr. Gerald Pfeffer (University of Calgary) used a specialized brain imaging technique called diffusion tensor image analysis along perivascular spaces (DTI-ALPS) to measure how well the glymphatic system was working in 45 participants living with ALS. Participants were recruited from the CALSNIC study (Canadian ALS Neuroimaging Consortium), supported by an ALS Canada-Brain Canada Arthur J Hudson Translational Team Grant. The study also included five participants with primary lateral sclerosis (PLS) and 22 healthy controls for comparison. Three brain scans were performed every four months to track changes, and researchers also looked at clinical factors such as age, sex, disease severity, and progression. 

The study found that glymphatic function seems to be reduced in people living with ALS compared to control groups. This reduction didn’t seem to be directly linked to any clinical factors, meaning someone with a rapid disease progression did not experience quicker glymphatic function decline compared to a slow progressor. However, researchers did note that glymphatic function seemed to decline with age, confirming past studies.  

These findings emphasize the importance of further exploring the glymphatic system in ALS, as this could help researchers to better understand the mechanisms underlying the buildup of misfolded proteins that contribute to motor neuron degeneration. Investigating the glymphatic system opens a new area with therapeutic potential for the disease, and future studies will need to explore how to properly target this system in people living with ALS.  

 

Questions about ALS research? Join us for ALS Research Clinicals Trials 101 Q&A: this monthly Q&A drop-in session is available for people living with ALS, their families, caregivers, and anyone close to someone living with the disease who is seeking information or might have questions about ALS research and/or clinical trials.  

 

Want to learn more about current clinical research in Canada? Join ALS Canada for our next ALS Clinical Trials Unboxed webinar to hear a Canadian or international investigator talking about their clinical trial and research. Watch past Unboxed webinars here. 

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