Multiple Sclerosis (MS) is an unpredictable neurological condition which affects the brain and spinal cord, potentially causing a wide range of symptoms including problems with vision, arm or leg movements, sensation, and balance.

Multiple Sclerosis (MS) is the most common autoimmune disorder of the Central Nervous System (CNS), affecting around 2.8 million people globally.

We spoke with Kirsi Kinnunen PhD, Senior Biomarker Scientist at IXICO ahead of this year’s World MS Day, to discuss how IXICO are supporting Multiple Sclerosis clinical trials to advance therapies for MS and other demyelinating diseases, by transforming brain imaging data into clinically meaningful insights.

Kirsi, what causes Multiple Sclerosis and other demyelinating diseases?

Unfortunately, we are still unsure of the cause of these diseases. All we know is that there are some risk factors that make some people more susceptible than others. In both MS and other demyelinating diseases, such as MOG Antibody Disease (MOGAD), the immune system goes haywire and damages the myelin sheath.

The myelin sheath is the protective tissue that surrounds the axons of nerve cells in the brain, spinal cord, and optic nerves. It allows the nerve cell to efficiently conduct signals from the cell body to the axon terminal for connection with other nerve cells. The confused immune system mistakenly attacks myelin, and in those with MOGAD it targets the MOG protein found on the myelin sheath.

Through brain imaging, we can see the result of this attack as one of three different types of lesions. As scientists and clinicians working on Multiple Sclerosis research studies, we are able to track these lesions as they develop, and design and test drug therapies to shrink them and stop them from developing more widely over time.

Why don’t we have an effective cure for Multiple Sclerosis or other demyelinating diseases?

We haven’t got an effective cure yet as the diseases themselves are so challenging, and the symptoms present differently in every patient. Given the causes can be genetic, environmental, or due to infection, it’s very difficult to find a cure because there are so many variations.

We do have successful disease-modifying therapeutics to aim to stop the immune attacks and reduce the frequency of MS flare-ups that patients with relapsing-remitting MS experience. However, these don’t usually slow down disease progression, as they can’t repair myelin damage or protect nerves.

What are the most significant MS clinical trials at the moment?

Through clinical trials, there are now a good number of disease-modifying therapeutics for treating relapsing-remitting Multiple Sclerosis and even a couple of therapies for progressive MS. There has been a significant increase in drug development over the past 20 years and there are now 19 plus drugs on the market for patients with all stages of the disease.

These disease-modifying treatments are positive for patients as they reduce the length of the relapse, and patients can be in remission for longer. The next challenge we face in MS clinical trials is to find a therapeutic that will stop disease progression in patients with MS and other demyelinating diseases.

Important efforts are underway to look at whether it is possible to achieve re-myelination. Reversing the demyelination process and regenerating the damaged myelin sheath would be a huge, game-changing breakthrough.

What has been IXICO’s role in clinical trials for MS and other demyelinating diseases?

Multiple Sclerosis clinical trials are a new area for IXICO. We have recently been working on MOGAD using imaging of the brain, spine and potentially the optic nerve, and these imaging techniques are consistently used across clinical trials in demyelinating diseases. In both cases, the neuroinflammation in both the brain and spine can be successfully tracked by imaging.

For MS and demyelinating disease diagnosis, imaging is crucial. It allows us to look for the hallmark lesions in the brain and spine.

What have been the biggest breakthroughs in MS clinical research in the last decade?

Over the last ten years, we have come a long way in Multiple Sclerosis research in terms of slowing the frequency of relapsing MS. Today, we have more than 19 effective therapeutics available, in comparison to the 1990s and early 2000s when there were really only four options for the treatment of MS: the interferons and copaxone.

For progressive Multiple Sclerosis, the clinical research into remyelination currently underway, is an important step towards finding new solutions for MS patients, and we look forward to learning more from this study.

What are the biggest challenges faced by MS clinical research?

The challenges of MS and demyelinating disease trials are similar to the difficulties in understanding the causes of these diseases – there are so many variables and patients present very differently.

There are lots of clinical trials for Multiple Sclerosis taking place, but it’s only in recent years that the more difficult aspects, such as halting progression or reversing the nerve damage are being considered as something we can address.

Why is the use of AI and data analysis so vital to Multiple Sclerosis research studies?

Advancements in data and analytics allow us to track imaging findings much faster, more accurately and more reliably. Previously, segmenting of lesions was done manually which was exceptionally time-consuming, as well as having a margin for human error. Using automated techniques to segment lesions means we can reduce the opportunity for error and improve accuracy.

At IXICO, we are also using trained AI algorithms to find and detect the right kind of lesion and be able to measure it. This process takes seconds, so it could be hugely beneficial for clinical trial eligibility screening.

For clinicians, the use of this technology to track a patient’s condition could be revolutionary. Multiple Sclerosis patients require regular imaging as part of their care, potentially having a scan every 6-24 months. Clinicians can use these tools to quickly look for any change or growth in a patient’s lesions, and spot new ones developing.

What is IXICO doing to support future MS clinical trials?

We are ready to support an increasing number of MS clinical trials, as we are experts in this area and have everything that’s needed to support these trials in terms of data acquisition and image analysis.

We have been using the core T2- and T1-weighted sequences for other disease areas for many years now and we’re able to support the advanced MS imaging that sponsors require – not just Magnetic Resonance Imaging (MRI), but also Positron Emission Tomography (PET).

Advanced MRI, including diffusion MRI and myelin-specific sequences, can be used for evaluating demyelination and/or axonal loss. Magnetic Resonance Spectroscopy (MRS) is another potentially interesting technique IXICO could support, which gives more direct imaging biomarkers than those available from MRI, and it’s completely non-invasive.

There has been some exciting work in the PET area recently, including repurposing the amyloid tracers that we've been using for years for Alzheimer’s disease clinical trials: tracers normally used to detect amyloid accumulation can be repurposed to look at myelin content in MS trials. Other tracers are available or in development to look at inflammation and neurodegeneration.

All in all, the future is certainly looking brighter for Multiple Sclerosis clinical research, and we hope that our work with trial sponsors will contribute considerably to finding a cure for MS one day in the future.

Find out more about IXICO

With our specialist neuroscience knowledge, AI-driven innovation, and robust operational infrastructure, IXICO solutions are specifically designed to enable sponsors to address core challenges and realize the full power of imaging biomarkers in their CNS clinical trials.

Click here to find out more about our neuroscience, data, and neuroimaging expertise for CNS trials.

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