World MS Day is celebrated on 30.05. Pioneering interdisciplinary work on multiple sclerosis (MS) is being carried out in pilot project coordinated by Neurocenter Finland, which have brought together excellence from various fields.

Neurocenter Finland is coordinating a project focusing on MS, consisting of two different entities. It is one of the six pilot projects funded by the Ministry of Social Affairs and Health, where the idea is to create synergies in research by bringing together top experts from various disciplines across the country.

“The goal of the MS pilot is to create new collaborative patterns and, through them, create new solutions for the prevention, treatment and diagnosis of MS,” explains Merja Jaronen, the Program Manager of Neurocenter Finland.

This interdisciplinary collaboration in the study of MS is already bearing fruit: in April, the Academy of Finland granted a five-year funding grant to Sanna Hagman, an Academy researcher at Tampere University who participated in the MS pilot, for the development of a human in vitro disease model. The study utilizes actual human cells.

“MS research is typically done through animal experiments, but because there are considerable differences between animals and humans, these results are difficult to apply and their accuracy is poor. With an interdisciplinary team, we are developing a platform to find new potential drug candidates for MS using human-derived cells,” says Sanna Hagman.

When neurons are placed in the same tissue culture dish, it is possible to measure the type of damage caused by glial cells to these neurons. By experimenting with different drugs, we are investigating whether the damage caused by glial cells to neurons can be prevented

Understanding progressive MS

Laura Airas, Professor of Neurology at Turku University Hospital (TYKS), who is the coordinator of the MS pilot, is also leading the pilot’s second subproject. It investigates the pathological mechanisms of MS and the risk genes for MS and their mechanisms of action.

“We’re trying to better understand what’s going on in the brain specifically for the progressive form of MS that currently lacks therapeutic options apart from supportive care,” Airas explains.

A subset of Airas’ study is involved in examining whether glial cells with a risk allele for MS and glial cells with a protective allele behave differently in cell cultures. This part of the project is a collaboration between Professor Airas and Sanna Hagman from the neurology group of Tampere University.

“When neurons are placed in the same tissue culture dish, it is possible to measure the type of damage caused by glial cells to these neurons. By experimenting with different drugs, we are investigating whether the damage caused by glial cells to neurons can be prevented,” Airas explains.

Airas’ project is unique because it combines data from cell culture with data from PET imaging of MS patients.

“We are able to genotype MS patients, that is, to see what kind of risk alleles they have for MS. PET imaging can directly look at different glial cell phenotypes in a living person. When this data is combined with results from cell culture, we get real, accurate data on the behavior of cells and the effects of drugs on these cells,” says Airas.

An interesting hypothesis in the study is that it could be potentially applied to other diseases involving neurodegenerative processes.

“The initial trigger in diseases can vary, but when the process starts in the brain, it can be similar regardless of the disease,” considers Airas.

Single cell-level samples for the development of targeted therapies

MS can be a very individually unique disease, and finding a pattern requires large amounts of data. The only way to find targeted therapies is through persistent basic research that can offer information about the causes and mechanisms of MS. The pilot’s second subproject, launched in autumn 2018, aims to build a nationwide operating model for more efficient collection of blood samples from MS patients.

“The idea is to systematically collect blood samples from MS patients at the biobank at different stages of the disease and medication. At the same time, the opportunity to collect live blood cells for freezing is utilized,” explains Pentti Tienari, Professor of Neuroimmunology at Helsinki University Hospital (HUS).

Research samples can be taken through the same injection as routine samples during medical appointments for MS patients.

“These can be used to study the effects of drugs and analyze the factors that affect their side-effects and efficacy,” Tienari says.

Over the last 15 years, biotechnology has evolved greatly, allowing the study of metabolic processes in single, individual cells. Such research brings a whole new level of detail to the identification of cells. For example, single-cell RNA sequencing may potentially identify a single hostile, MS-causing leukocyte from a large number of cells.

“Once the sample data are large enough, we can analyze the characteristics of these MS-causing leukocytes, which is a prerequisite for developing targeted therapies that focus on such hostile ‘terrorist’ cells,” Tienari says.