title: Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial.
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.
authors.affiliation: Department of Neurology Eastern Piedmont University, Maggiore della Carità Hospital, 28100 Novara, Italy. mazzini.l@libero.it
authors.forename: L
authors.initials: L
authors.lastname: Mazzini
authors.forename: I
authors.initials: I
authors.lastname: Ferrero
authors.forename: V
authors.initials: V
authors.lastname: Luparello
authors.forename: D
authors.initials: D
authors.lastname: Rustichelli
authors.forename: M
authors.initials: M
authors.lastname: Gunetti
authors.forename: K
authors.initials: K
authors.lastname: Mareschi
authors.forename: L
authors.initials: L
authors.lastname: Testa
authors.forename: A
authors.initials: A
authors.lastname: Stecco
authors.forename: R
authors.initials: R
authors.lastname: Tarletti
authors.forename: M
authors.initials: M
authors.lastname: Miglioretti
authors.forename: E
authors.initials: E
authors.lastname: Fava
authors.forename: N
authors.initials: N
authors.lastname: Nasuelli
authors.forename: C
authors.initials: C
authors.lastname: Cisari
authors.forename: M
authors.initials: M
authors.lastname: Massara
authors.forename: R
authors.initials: R
authors.lastname: Vercelli
authors.forename: G D
authors.initials: GD
authors.lastname: Oggioni
authors.forename: A
authors.initials: A
authors.lastname: Carriero
authors.forename: R
authors.initials: R
authors.lastname: Cantello
authors.forename: F
authors.initials: F
authors.lastname: Monaco
authors.forename: F
authors.initials: F
authors.lastname: Fagioli
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology / Q000601:surgery*; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000502:physiology; D015331:Cohort Studies; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D004558:Electric Stimulation / Q000379:methods; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D012189:Retrospective Studies; D013116:Spinal Cord / Q000473:pathology; D013997:Time Factors; D055815:Young Adult
chemical_list: D015703:Antigens, CD