The Niche

More stem cells in Lou Gehrig’s disease

Shortly after my coverage of the FDA’s approval for NeuralStem’s stem-cell trial for amyotrophic lateral sclerosis appeared on the Niche, Letizia Mazzini and Franca Fagioli of Eastern Piedmont University contacted me to tell me about their team’s work using mesenchymal stem cells for the same disease. While Neuralstem is moving forward with neural stem cells, Mazzini and colleagues have been exploring the use of mesenchymal stem cells derived from the patient who will receive them. She has recently published results of a Phase I trial as well as a review of stem-cell approaches in ALS. Unfortunately, I learned of this work only after I’d posted.

Here is their letter:

We have just read, not without some interest, the NeuralStem communicate. The trial is presented as if it were the first clinical study with stem cells in ALS (“This is the first stem-cell approach for ALS” says Lucie Bruijin). However, this needs to be rectified as we conducted two phase 1 clinical trials one in 2001 (Mazzini et al., 2008)) and the other in 2007 (Mazzini L et al., 2009). The trials were approved respectively by the regional Ethical Committee and by the Italian Institute of Health and by the and were designed to test the safety and the feasibility of mesenchymal stem cell transplantation into the spinal cord of ALS patients.

MSC were isolated from patients’ bone marrow, in vitro expanded for 3-4 passages and evaluated for quality control as requested by national rules on advanced therapies. In neither of our trials were there any immediate or delayed transplant related toxicities. Stem cells were transplanted into the spinal cord at the thoracic levels with a surgical approach. Clinical, laboratory, and radiographic evaluations of the patients showed no serious transplant related adverse events. Magnetic resonance images (MRI) showed no structural changes (including tumor formation) in either the brain or the spinal cord.

Furthermore, we also demonstrated that expanded MSCs can survive and migrate after transplantation in the lumbar spinal cord of SOD1-G93A mice, where they prevent astrogliosis and microglial activation and delay the ALS-related decrease in the number of motor neurons, resulting in an amelioration of motor performance (Vercelli A et al., 2008 ). Therefore we concluded that MSCs represent a good source of stem cells for future ALS cell based clinical trials.

Thus, the NeuralStem trial, as it appears, shows this experimental design to be no different to our studies except for the cell type: neural stem cell derived from a 8-week fetus.

Letizia Mazzini, MD ALS Centre, Dpt of Neurology ,Eastern Piedmont University Maggiore della Carità Hospital Novara, Italy

Franca Fagioli, MD Stem Cell Transplantation and Cellular Therapy Unit Pediatric Onco-Hematology Department Regina Margherita Children’s Hospital Torino. Italy


1.Mazzini, L. & Mareschi, K.& Ferrero, I.& Vassallo, E.& Oliveri, G.& Nasuelli, N.& Oggioni, GD.& Testa, L.& Fagioli F. Stem cell treatment in Amyotrophic Lateral Sclerosis. Journal of the Neurological Sciences 265 (2008) 78–83 (PubMed link)

2. Mazzini L, Ferrero I, Luparello V, Rustichelli D, Gunetti M, Mareschi K, Testa L, Stecco A, Tarletti R, Miglioretti M, Fava E, Nasuelli N, Cisari C, Massara M, Vercelli R, Oggioni GD, Carriero A, Cantello R, Monaco F, Fagioli F Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial.Exp Neurol. 2009 Aug 13. (PubMed link)

3. Alessandro Vercelli, Oana M Mereuta, MD; Diego Garbossa, MD; Giuseppe Muraca; Katia Mareschi; Deborah Rustichelli; Ivana Ferrero; Letizia Mazzini, MD; Enrico Madon, MD; Franca Fagioli, MD Human mesenchymal stem cell transplantation extends survival, improves motor performance and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis

Neurobiology of disease. 31 (2008) 395–405 (PubMed link)

For Nature Reports coverage of mesenchymal stem cells in other clinical indications, see Questioning the Self Cell and Stem-cell drug fails crucial trials


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