Researchers find new therapeutic targets for MS
image: MS therapeutic target infographic
Credit: Netherlands Institute for Neuroscience
Researchers from the Netherlands Institute for Neuroscience (NIN) have discovered new potential therapeutic targets for multiple sclerosis (MS). While current treatments prevent further damage, the current findings may form the starting point for the development of new treatments for tissue recovery in MS.
Multiple Sclerosis (MS) is a chronic disease in which the immune system mistakenly attacks the central nervous system. This leads to lesions with localized inflammation, causing damage to the insulating sheath of nerve cells, known as myelin. As a result, individuals with MS may experience a wide range of neurological symptoms, including difficulties with walking, speech, and vision.
There are currently no regenerative treatments for MS, only treatments that can prevent new attacks from the immune system. With financial support from the Start2Cure foundation, Inge Huitinga and Joost Verhaagen, from the Netherlands Institute for Neuroscience, have established a collaboration with the aim to develop a regenerative gene therapy for MS.
A new approach
To identify potential targets that can promote recovery, Alida Chen, first author of the study, investigated brain tissue from a unique and well-characterized MS autopsy cohort of the Netherlands Brain Bank. These donors either had very well-recovered myelin, or poorly recovered myelin in MS lesions.
Chen looked into the locations of the brain where the myelin had naturally recovered and was still actively recovering. She was able to find genes and pathways that are associated with myelin repair and could potentially promote this restoration process. “We are not the first to study MS using human brain tissue, but we are the first to compare transcriptomic data of MS donors with differing recovering potential”, she explains.
“MS donors can have several different types of lesions”, Chen adds. “These can be classified based on the shape of the immune cells of the central nervous system, also known as microglia”. It turns out that the appearance of these microglia also plays a pivotal role in determining the success of tissue recovery. “This gives an important first indication of where to exactly look for targets for future treatments.”
The Start2Cure Pipeline
Now that Chen has identified promising targets by comparing lesions with poorly recovered and well-recovered myelin, researchers from Joost Verhaagen’s group have started working on state-of-the-art viral vector technology, which can use safe, inactive viruses to deliver these targets in a cell-specific way to the brain. Their ability to promote recovery can then be tested in models for MS.
“One of our big strengths is that we start our research with human tissue. Now we have a strong starting point to confirm and explore those findings using other methods, like cells or mice”, Chen explains.
Promising results
Chen’s findings are fully accessible for researchers globally. “Now that we have identified several genes associated with high myelin recovering potential, we expect these pathways and targets to become a rich source of information, so that other researchers can also develop new therapies to aid tissue recovery in MS”, Chen adds.
“These findings are clinically very relevant: all our effective treatments are solely focused on preventing new MS lesions. There aren’t any drugs that promote repair of damaged brain tissue that we, as neurologists, can offer our MS patients. The current findings provide numerous angles to investigate and potentially develop such treatments. This gives hope for better therapies in the long run ”, Joost Smolders, neurologist at the Erasmus Medical Centre and a co-author on the study, adds.
Source: BRAIN
About the Netherlands Institute for Neuroscience
The Netherlands Institute for Neuroscience (NIN) is a leading research institute dedicated to understand the neural circuits that create our mental functions and how they change in brain disorders. The NIN achieves this by combining innovative research, state-of-the-art technology, and interdisciplinary collaboration.
About the Start2Cure foundation
The Start2Cure Foundation was founded with the goal of improving the quality of life of people with progressive Multiple Sclerosis in the short term, and bringing a cure for the disease closer in the long term. The foundation provides grants for both medical scientific research and social initiatives. Read more about the Start2Cure Foundation using the following links: