0000000000729223
AUTHOR
Gianluigi Mancardi
Intraspinal stem cell transplantation for amyotrophic lateral sclerosis: Ready for efficacy clinical trials?
Intraspinal stem cell (SC) transplantation represents a new therapeutic approach for amyotrophic lateral sclerosis (ALS) clinical trials. There are considerable difficulties in designing future efficacy trials, some related to the field of ALS and some that are specific to SCs or the mode of delivery. In October 2015, the most controversial points on SC transplantation were addressed during an international workshop intended to bring together international SC and ALS researchers in a public discussion on a topic for which expertise is limited. During the meeting, a discussion was started on the basic structure of the ideal clinical trial testing the efficacy and safety of SC transplantation…
Repeated courses of granulocyte colony-stimulating factor in amyotrophic lateral sclerosis: Clinical and biological results from a prospective multicenter study
Granulocyte colony-stimulating factor (G-CSF) induces a transient mobilization of hematopoietic progenitor cells from bone marrow to peripheral blood. Our aim was to evaluate safety of repeated courses of G-CSF in patients with amyotrophic lateral sclerosis (ALS), assessing disease progression and changes in chemokine and cytokine levels in serum and cerebrospinal fluid (CSF). Twenty-four ALS patients entered an open-label, multicenter trial in which four courses of G-CSF and mannitol were administered at 3-month intervals. Levels of G-CSF were increased after treatment in the serum and CSF. Few and transitory adverse events were observed. No significant reduction of the mean monthly decrea…
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
© 2018 Elsevier Inc.
Natalizumab: a country-based surveillance program
Natalizumab is a humanized monoclonal antibody with a selective adhesion-molecule inhibitor effect, and a demonstrated efficacy in decreasing the frequency of relapses and progression of disability in relapsing-remitting multiple sclerosis (RR MS). After the approval of FDA and EMEA in MS cases unresponsive to immunomodulating therapy or in severe MS patients also not previously treated with interferons, and considering the concern on the possible side effects, an accurate program of surveillance was organized in our country by a combined effort of AIFA, Cineca, Department of Pharmacology of University of Bologna, and a group of neurologists appointed by the National Society of Neurology (S…
HFE p.H63D polymorphism does not influence ALS phenotype and survival.
It has been recently reported that the p.His63Asp polymorphism of the HFE gene accelerates disease progression both in the SOD1 transgenic mouse and in amyotrophic lateral sclerosis (ALS) patients. We have evaluated the effect of HFE p.His63Asp polymorphism on the phenotype in 1351 Italian ALS patients (232 of Sardinian ancestry). Patients were genotyped for the HFE p.His63Asp polymorphism (CC, GC, and GG). All patients were also assessed for C9ORF72, TARDBP, SOD1, and FUS mutations. Of the 1351 ALS patients, 363 (29.2%) were heterozygous (GC) for the p.His63Asp polymorphism and 30 (2.2%) were homozygous for the minor allele (GG). Patients with CC, GC, and GG polymorphisms did not significa…
Cyclophosphamide Pulse Therapy after Natalizumab Discontinuation for Multiple Sclerosis: a multicenter study.
Importance: Natalizumab discontinuation induces the recurrence of Multiple Sclerosis (MS) disease activity: Currently no therapeutic approach has been found able to abolish disease reactivation. Objective: To collect data from patients with MS switching from natalizumab to cyclophosphamide. Design: Retrospective multicentre study. Setting: Nine Multiple Sclerosis Centers in Italy. Participants: A total of 47 patients with clinically definite RR-MS switched to cyclophosphamide after natalizumab discontinuation. Two patients were excluded from the analysis because received less than 12 natalizumab infusions. The remaining 45 patients were subdivided into two main groups: Early Treatment (peri…