STOCKHOLM – The infusion of mesenchymal stem cells in people with multiple sclerosis is a safe procedure. This has been confirmed by preliminary data from the MESEMS study, the first international study of its kind, presented at ECTRIMS by Antonio Uccelli, Scientific Director of San Martino Hospital, Genoa and co-principal investigator of the MESEMS study along with Mark Freedman, Professor of Neurology at the Ottawa Hospital Research Institute, Canada.

The recently concluded phase II, double-blind, multi-center study involved 10 countries, with the aim of verifying the safety and efficacy of autologous mesenchymal stem cells for the treatment of multiple sclerosis. While results provide evidence of the safety of intravenous administration of mesenchymal stem cells, with no difference compared to placebo, the study was unable to show an effect on decreasing brain inflammation, determined by the number of gadolinium enhancing lesions detected by magnetic resonance imaging of the brain.

Researchers expect to learn more with further analyses of secondary outcomes, to be concluded in the upcoming months. “An early analysis showed that MSC demonstrated an important trend towards decreasing annualized relapse rate over 24 weeks between active treatment and placebo. In the next weeks we will start the analysis of the treatment on several other clinical and MRI parameters aimed at detecting the effects on neuroprotection and repair in individuals who received the active treatment”, explains Uccelli. Preliminary analyses concentrated on the study sample as a whole, while it’s likely that individual patients did have a positive outcome with treatment and others did not, for example patients with a relapsing-remitting phase compared to those in a progressive phase. “We’re confident additional results will provide us with crucial indications. Demonstrating the safety of this treatment is an important preliminary result and, depending on further analyses of secondary outcomes, we will hopefully clarify the role of mesenchymal stem cells in neuroprotection, and thus, provide further hope for people living MS”, concludes Uccelli.

The MESEMS study

The clinical study, called MESEMS (MEsenchymal StEm cells for Multiple Sclerosis) is an academic, investigator-initiated, randomized, double-blind, placebo-compared phase II clinical trial with autologous, bone-marrow derived MSC in MS. Enrolled subjects received autologous MSC at either baseline or at week 24, through a cross-over design. Primary co-objectives are to test safety and efficacy of MSC treatment compared to placebo at 6 months. Secondary objectives will evaluate the efficacy of MSC at clinical and MRI levels. In order to overcome funding constraints, the MESEMS study has been designed to merge partially independent clinical trials, following harmonized protocols and sharing some key centralized procedures, including data collection and analyses. This study is today the largest ever performed with mesenchymal stem cells on patients with MS.

Nine countries adhere to the MESEMS network, based in Italy (Genova, Milano, and Verona), Canada (Ottawa and Winnipeg), Austria (Salzburg), Denmark (Copenhagen), France (Toulouse), Iran (Tehran), Spain-Andalusia (Cordoba, Malaga, and Sevilla), Spain-Catalonia (Badalona), Sweden (Stockholm), and the United Kingdom (London). Centralized MRI reading and analyses were performed at the Medical Image Analysis Center (MIAC AG) in Basel, Switzerland, an imaging Contract Research Organization (CRO) specialized in phase II/III studies.

Non-profit organizations and academic entities funded the trial. In details the MESEMS network received a grant from Fondazione Italiana Sclerosi Multipla (FISM; sponsor of the Italian Clinical Trial, of the CRO activities and of part of centralized MRI activities). Multiple Sclerosis Society of Canada (sponsor of canadian clinical trial). European Committee for Multiple Sclerosis (ECTRIMS), Multiple Sclerosis International Foundation (MSIF) for centralized activities. Financial support was obtained also from The Danish Multiple Sclerosis Society, The Toyota Foundation, and Danish Blood Donors’ Research Foundation (Denmark); Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria (Austria), ARSEP Foundation, AFM (France), UK MS Society, NIHR Biomedical Research Centre funding scheme to Imperial College and by the NIHR Imperial Clinical Research Facility (UK); The Karolinska Institutet, (Sweden); Iniciativa Andaluza en Terapias Avanzadas, Junta de Andalucía and Instituto de Salud Carlos III (Spain); The Royan Institute for Reproductive Medicine and Stem Cells (Iran).

The study included a total of 144 subjects with MS still active (ie with relapses and / or with radiological evidence of active disease), one third in the progressive phase of disease, not responsive to available therapies. The last patient enrolled in the trial has performed his/her last visit in July 2019, thus allowing to start data analysis of the trial results, that will be disseminated at the ECTRIMS conference.