Brain stem cell transplantation in patients with secondary progressive multiple sclerosis is safe, very well tolerated and may have a lasting protective effect against further damage to the patient's brain.
This is the conclusion of a study coordinated by the IRCCS Casa Sollievo della Sofferenza (CSS) in San Giovanni Rotondo and designed by Prof. Angelo Vescovi of the University of Milan - Bicocca, Scientific Director of the same IRCCS, in collaboration with Prof. Stefano Pluchino of the University of Cambridge (UK).
The results of this phase 1 clinical trial, published in the prestigious journal Cell Stem Cell - which has dedicated the title page to it - finally pave the way for phase 2 clinical trials in this devastating disease.
For the first time in humans, neural stem cells were transplanted directly into the lateral ventricles of the brain in 15 patients with advanced secondary progressive multiple sclerosis.
The study represents an important step in the development of advanced cell therapies for progressive forms of multiple sclerosis, a disease for which there is currently no curative therapy. The AOSP S. Maria di Terni, the University of Colorado and the Ente Ospedaliero Cantonale (EOC) in Lugano, Switzerland, which centralised the interpretation of radiological images, also participated in the trial. The study, partly funded by the CARIT Foundation (Terni) and generously supported by the Region of Apulia, was initiated by Monsignor Vincenzo Paglia, President of the Pontifical Academy for Life of the Vatican State.
As Professor Vescovi points out, the brain stem cells used are free of ethical problems, since they are isolated from foetuses that have died of natural causes. Most importantly, a virtually unlimited number of these stem cells could be obtained from a single donor. This means that in future trials it will be possible to use the same cells for all treatments, solving the major problem of lack of reproducibility between different studies, mainly due to the use of cells from different donors.
The transplant patients were followed for 12 months. No deaths or serious adverse events related to the treatment were observed throughout the year. Side effects were mild, transient and reversible.
All patients had a high degree of disability at the start of the clinical trial - for example, they were wheelchair-bound - but during the 12-month observation period they showed no increase in disability or worsening of symptoms. None of the patients showed symptoms that would indicate a relapse or signs of clinical progression, suggesting substantial stability of the pathology.
A noteworthy aspect also emerged from the post-transplant assessment of 'total brain volume'. In transplanted patients, it was observed that the higher the dose of stem cells transplanted, the greater the reduction in brain volume. The hypothesis is that this phenomenon may be related to an anti-inflammatory or even neuroprotective effect due to the action of the injected brain stem cells.
This interpretation was further supported by the relevant molecular changes produced by the brain stem cells in the course of the clinical trial. Indeed, in the cerebrospinal fluid (the fluid that bathes the brain and its cavities) of the transplanted patients, the researchers measured changes in the levels of certain molecules associated with the mechanisms by which nerve tissue uses and metabolises fatty acids, including for energy production. It was observed that the higher the dose of stem cells transplanted, the higher the levels of fatty acids found in the patients' cerebrospinal fluid. Remarkably, the levels remained high for at least one year after transplantation.
Professor Stefano Pluchino said: "There is an urgent need to develop new treatments for progressive forms of MS and we are very pleased with the results we have obtained, which represent a fundamental step forward in the development of cell therapies for the treatment of MS".
Prof Angelo Vescovi commented: "We are aware that our study has limitations related to its small size and possible confounding effects due to immunosuppressive drugs - however, the fact that our treatment is safe and that the effects correlate with the amount of cells injected and last for more than 12 months means that we can proceed to the next stage, means that we can proceed to the next phase of the clinical trial (Phase 2), also thanks to the availability of stem cells already produced and stored in the GMP workshop (authorised by AIFA) of Casa Sollievo della Sofferenza, thanks to which - in the only case in the world - the availability of the cellular drug will no longer be a problem. "
The two scientists concluded: 'It has taken almost 30 years since the discovery of brain stem cells to arrive at this experimental therapeutic treatment. The way is now clear for larger efficacy studies to follow shortly'.