A history of Amyotrophic Lateral Sclerosis (ALS)
aka Lou Gehrig’s disease
and stem cell treatments for humans going back to 2001.
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)
ADDITIONAL STUDIES IN CHRONOLOGICAL ORDER (may be some repetition)
2003 – Stem cell therapy in amyotrophic lateral sclerosis: a methodological approach in humans
Our results appear to demonstrate that the procedures of ex vivo expansion of autologous mesenchymal stem cells and of transplantation into the spinal cord of humans are safe and well tolerated by ALS patients. Read More: http://informahealthcare.com/doi/abs/10.1080/14660820310014653
2003 – Amyotroph Lateral Scler Other Motor Neuron Disord – Letizia Mazzini and colleagues (Amyotroph Lateral Scler Other Motor Neuron Disord 2003; 4: 158—61) injected autologous bone-marrow-derived stem cells into the spinal cord of seven ALS patients. These investigators reported that the procedure had a reasonable margin of clinical safety. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2804%2916634-8/fulltext
2007 – Stem cell treatment in Amyotrophic Lateral Sclerosis
Journal of the Neurological Sciences xx (2007) xxx– xxx – The results of the long term follow-up (more than 4 years) confirm that intraspinal injection of MSCs in ALS patients is safe as previously reported. – http://fondazionevialliemauro.it/eng/PDF/JNS.pdf
2008 – Stem cell treatment in Amyotrophic Lateral Sclerosis
Journal of the Neurological Sciences – Volume 265, Issue 1 , Pages 78-83, 15 February 2008 – Our results seem to demonstrate that MSCs represent a good chance for stem cell cell-based therapy in ALS and that intraspinal injection of MSCs is safe also in the long term. A new phase 1 study is carried out to verify these data in a larger number of patients.
2009 – Stem Cell treatment of ALS has a history of success since Feb
“In a [February, 2009] published clinical stem cell research study, adult stem cells were shown to help delay Amyotrophic Lateral Sclerosis (ALS) progression and improve an ALS patient’s quality of life. This research study was believed to be the first published study comparing ALS patients who had their own stem cells injected into their brain vs a control group…
The initial two year clinical test study results of the stem cell procedure was published in Cytotherapy, February, 2009. Positive results were confirmed through both clinical observation and MRI tractography. It is considered by many within the international neurological community to be the foremost procedure available for minimizing or abrogating ALS symptoms and extending the lifespan of ALS patients. The procedure is a state of the art use of autologous CD-133 (+) stem cells injected into the frontal cortices for the effective replacement of motor neurons.”
The initial two year clinical test study results of the stem cell procedure instituted by Hospital San Jose Tecnologico de Monterrey, was published in Cytotherapy, February, 2009. Positive results were confirmed through both clinical observation and MRI tractography. It is considered by many within the international neurological community to be the foremost procedure available for minimizing or abrogating ALS symptoms and extending the lifespan of ALS patients. The procedure is a state of the art use of autologous CD-133 (+) stem cells injected into the frontal cortices for the effective replacement of motor neurons.
THE TRIAL: http://www.alsworldwide.net/pdfs/monterey_hospital.pdf
2012 – BrainStorm sees positive data in ALS stem cell trial
TEL AVIVTue Jan 17, 2012 12:07am EST - (Reuters) – Data from the first ALS patients in a clinical trial treated with BrainStorm Cell Therapeutics adult stem cell therapy did not show significant side effects and the treatment has so far proven to be safe, the company said on Tuesday…http://www.reuters.com/article/2012/01/17/us-brainstorm-trial-embargoed-idUSTRE80G07Q20120117?feedType=nl&feedName=ushealth1100