The innovation of this study is represented by the use of a new advanced cell therapy based on neural stem cells never used before in patients with multiple sclerosis. These cells, unlike hematopoietic stem cells (used in relapsing remitting forms of disease but ineffective in progressive forms) and mesenchymal stem cells (which have not shown benefits in patients with progressive multiple sclerosis), have shown in preclinical studies conducted in the laboratory of being able to have a high pro-regenerative potential once transplanted.
Neural stem cells represent a promising therapeutic strategy for a complex and heterogeneous disease such as multiple sclerosis, in which there are multiple mechanisms that contribute to the progression of disability – from inflammation to neurodegeneration – and which need to be addressed to develop an effective treatment. It was primarily thanks to the support of the Italian Multiple Sclerosis Association (AISM) and its Foundation (FISM) that this therapy, the result of 20 years of research, reached clinical trials.
“The one achieved is an important goal, even if it represents only the first stage of the clinical-experimental path that leads to a real therapy. My first thoughts go, above all, to the sick people and their families who have supported our research in all these years, certainly dramatic from the point of view of public health, with patience, hope, dedication and sacrifice. We would not have gotten this far without their contribution. However, the road taken is still long”, explains Gianvito Martino, scientific director of San Raffaele.
“The published data are not yet sufficient to consider this opportunity as a real therapy. The next step will be to proceed with a new experimental clinical study involving a larger group of patients, with the aim of demonstrating , on the one hand the efficacy of neural stem cells in blocking the progression of the disease, on the other hand their ability to promote the regeneration of damaged areas of the nervous system.The ultimate goal, which is the great challenge we have decided to face 20 years ago, is to develop an innovative and effective therapy for people with progressive forms of MS who have, to date, limited therapeutic options”, concludes Professor Martino.
“For over twenty years we have promoted and supported research on stem cells, investing in basic research and experimentation on humans. Scientific research times are apparently long, but this is how we can arrive at results that are concretely capable to change people’s lives. This is the research we want and which we finance. In the last twenty-five years, a lot has changed in multiple sclerosis, a lot is also being done for the progressive forms. The most seriously ill people have innovative answers to deal with the symptoms and gain quality of life, also through rehabilitation.We will continue to develop this research with stem cells and other innovative projects to move towards a world free from multiple sclerosis” declares Mario Alberto Battaglia, president of the Italian Multiple Sclerosis Foundation (FISM). The scientific foundations of this trial were laid in a series of works by Gianvito’s group Martino who, between 2003 and 2009, demonstrated the efficacy of neural stem cell transplantation in multiple preclinical experimental models of multiple sclerosis.
Lo studio STEMS – The experimental therapy on which the STEMS study is based consists of an infusion of neural stem cells through a lumbar puncture which introduces them directly into the cerebrospinal fluid, through which they can reach the brain and spinal cord which are the sites affected by sclerosis multiple and in which the cells could carry out their action. Neural stem cells are progenitor cells capable of specializing into all types of nerve cells. In animal models it has been demonstrated that these cells, once transplanted, are able to reach brain and spinal cord lesions precisely because they are attracted by the damage. Once these lesions have been reached, the cells do not specialize, but promote neuroprotection and repair mechanisms by releasing immunomodulatory and pro-regenerative substances.
The study involved 12 people with progressive MS and high disability who had already tried the therapies currently available with little or no success. The patients were divided into 4 groups, of 3 patients each, who received, with a single lumbar puncture, an increasing number of cells, from about 50 million cells for the first group up to 500 million for the first group. the last one. The cells used for the transplant are of fetal origin and were prepared thanks to the collaboration with the Stefano Verri Cell Therapy Laboratory, supported by the Matilde Tettamanti and Menotti De Marchi Onlus Foundation and with the IRCCS Ca’ Granda Ospedale Maggiore Policlinico Foundation.