Is it too soon for Mesenchymal Stem Cell trials in people with ALS?

Neurology Clinical Trials Unit, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Amyotrophic Lateral Sclerosis (Impact Factor: 2.37). 10/2008; 9(6):321-2. DOI: 10.1080/17482960802425559
Source: PubMed


Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting primarily the motor neurons. Stem cell therapy is under development as a possible treatment approach. A pilot study of intraspinal injections of mesenchymal stem cells (MSC) was conducted in 9 participants. We review this paper, the rationale, preclinical data and study design.

6 Reads
  • Source
    • "Moreover, expanded MSCs can survive and migrate after transplantation in the lumbar spinal cord of SOD1G93A mice, where they prevent astrogliosis and microglial activation and delay ALS-related decrease in the number of motoneurons , resulting in an amelioration of motor performance (Vercelli et al., 2008). Early clinical investigations indicated that transplantation of autologous MSCs into the spinal cord is feasible in ALS patients (Mazzini et al., 2003, 2006, 2008) however as that study was limited to 9 patients, the safety of intraspinal transfer of MSCs for ALS leaves some questions relative to the results open (Badayan and Cudkowicz, 2008). We therefore performed a Phase I trial for a further assessment of the feasibility and toxicity of the procedure and to test the impact of a cell therapy approach in patients. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Amyotrophic Lateral Sclerosis (ALS) is a devastating incurable disease. Stem-cell-based therapies represent a new possible strategy for ALS clinical research. The objectives of this Phase 1 clinical study were to assess the feasibility and toxicity of mesenchymal stem cell transplantation and to test the impact of a cell therapy in ALS patients. The trial was approved and monitored by the National Institute of Health and by the Ethics Committees of all participating Institutions. Autologous MSCs were isolated from bone marrow, expanded in vitro and analyzed according to GMP conditions. Expanded MSCs were suspended in the autologous cerebrospinal fluid (CSF) and directly transplanted into the spinal cord at a high thoracic level with a surgical procedure. Ten ALS patients were enrolled and regularly monitored before and after transplantation by clinical, psychological, neuroradiological and neurophysiological assessments. There was no immediate or delayed transplant-related toxicity. 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. However the lack of post mortem material prevents any definitive conclusion about the vitality of the MSCs after transplantation. In conclusion, this study confirms that MSC transplantation into the spinal cord of ALS patients is safe and that MSCs might have a clinical use for future ALS cell based clinical trials.
    Experimental Neurology 09/2009; 223(1):229-37. DOI:10.1016/j.expneurol.2009.08.007 · 4.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The design of low density parity check (LDPC) codes with minimum mean squared error (MMSE) turbo equalization is considered. Techniques to compute the probability density function of the extrinsic information at the output of the equalizer and the decoder are discussed. Using these techniques, it is shown that thresholds can be computed for LDPC codes for intersymbol interference (ISI) channels and good LDPC code ensembles can be designed. The distinct features of this work include: (1) The input-output pdf of the equalizer is expressed in closed-form, and evaluated analytically - no simulation of the equalizer or the code is needed during the design process; (2) ISI channels with very long memory can be easily handled; (3) Codes for fading ISI channels can be designed without the need for extensive numerical computation.
    Information Theory, 2002. Proceedings. 2002 IEEE International Symposium on; 02/2002
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: CONTEXT: With the lack of effective drug treatments for amyotrophic lateral sclerosis (ALS), and compelling preclinical data, stem-cell research has highlighted this disease as a candidate for stem-cell treatment. Stem-cell transplantation is an attractive strategy for neurological diseases and early successes in animal models of neurodegnerative disease generated optimism about restoring function or delaying degeneration in human beings. The restricted potential of adult stem cells has been challenged over the past 5 years by reports on their ability to acquire new unexpected fates beyond their embryonic lineage (transdifferentiation). Therefore, autologous or allogeneic stem cells, undifferentiated or transdifferentiated and manipulated epigenetically or genetically, could be a candidate source for local or systemic cell-therapies in ALS. STARTING POINT: Albert Clement and colleagues (Science 2003; 302: 113-17) showed that in SOD1G93A chimeric mice, motorneuron degeneration requires damage from mutant SOD1 acting in non-neuronal cells. Wild-type non-neuronal (glial) cells could delay degeneration and extend survival of mutant-expressing motorneurons. 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. WHERE NEXT? The success of cell-replacement therapy in ALS will depend a lot on preclinical evidence, because of the complexity and precision of the pattern of connectivity that needs to be restored in degenerating motoneurons. Stem-cell therapy will need to be used with other drugs or treatments, such as antioxidants and/or infusion of trophic molecules.
    The Lancet 07/2004; 364(9429):200-2. DOI:10.1016/S0140-6736(04)16634-8 · 45.22 Impact Factor
Show more