showing 10 related works from this author
Repeated courses of granulocyte colony-stimulating factor in amyotrophic lateral sclerosis: Clinical and biological results from a prospective multic…
2011
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
© 2018 Elsevier Inc.
HFE p.H63D polymorphism does not influence ALS phenotype and survival.
2015
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…
C9ORF72 in a Large Series of Italian and Sardinian Familial and Sporadic ALS Patients (IN9-1.003)
2012
Objective: To assess the frequency and the phenotype of a large series of Italian sALS and fALS with C9ORF72 repeat expansions. Background Recently we found that large expansions of hexanucleotide repeats (GGGGCC) in the first intron of the C9ORF72 gene, located in the chromosome 9p21, are related to familial and sporadic ALS cases(Renton et al, 2011). Design/Methods: We assessed 126 index fALS (106 Italians, 20 of Sardinians) and 601 sALS (485 Italians, 116 Sardinians), negative for other ALS-related genes mutations. Patients were collected through the ITALSGEN consortium. Repeat primer PCR to screen the presence of the hexanucleotide expansion in the first intron of C9ORF72 have been perf…
Allele-specific silencing as therapy for familial amyotrophic lateral sclerosis caused by the p.G376D TARDBP mutation
2022
Abstract Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by the degeneration of motor neurons. There is no treatment for this disease that affects the ability to move, eat, speak and finally breathe, causing death. In an Italian family, a heterozygous pathogenic missense variant has been previously discovered in Exon 6 of the gene TARDBP encoding the TAR DNA-binding protein 43 protein. Here, we developed a potential therapeutic tool based on allele-specific small interfering RNAs for familial amyotrophic lateral sclerosis with the heterozygous missense mutation c.1127G>A. We designed a small interfering RNA that was able to diminish specifically the express…
A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis
2009
The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 …
FUS mutations in sporadic amyotrophic lateral sclerosis
2011
Mutations in the FUS gene have recently been described as a cause of familial amyotrophic lateral sclerosis (ALS), but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of all coding exons of FUS in 228 sporadic ALS cases, and, as previous reports suggest that exon 15 represents a mutational hotspot, we sequenced this exon in an additional 1295 sporadic cases. Six variants in six different cases were found, indicating that FUS mutations can underlie apparently sporadic ALS, but account for less than 1% of this form of disease. © 2010 .
CONSISTENT BONE MARROW-DERIVED CELL MOBILIZATION FOLLOWING REPEATED SHORT COURSES OF GRANULOCYTE-COLONY-STIMULATING FACTOR IN PATIENTS WITH AMYOTROPH…
2009
Background and aims. The aim of this study was to evaluate and characterize the feasibility and safety of bone marrow-derived cell (BMC) mobilization following repeated courses of granulocyte-colony stimulating factor (G-CSF) in patients with amyotrophic lateral sclerosis (ALS). Methods. Between January 2006 and March 2007, 26 ALS patients entered a multicenter trial that included four courses of BMC mobilization at 3-month intervals. In each course, G-CSF (5 mu g/kg b.i.d.) was administered for four consecutive days; 18% mannitol was also given. Mobilization was monitored by flow cytometry analysis of circulating CD34(+) cells and by in vitro colony assay for clonogenic progenitors. Co-exp…
Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area
2016
Tafamidis is a transthyretin (TTR) stabilizer able to prevent TTR tetramer dissociation. There have been a few encouraging studies on Tafamidis efficacy in early-onset inherited transthyretin amyloidosis (ATTR) due to Val30Met mutation. However, less is known about its efficacy in later disease stages and in non-Val30Met mutations. We performed a multi-center observational study on symptomatic ATTR patients prescribed to receive Tafamidis. We followed up patients according to a standardized protocol including general medical, cardiological and neurological assessments at baseline and every 6 months up to 3 years. Sixty-one (42 males) patients were recruited. Only 28 % of enrolled subjects h…
Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS
2010
Summary Using exome sequencing, we identified a p.R191Q amino acid change in the valosin-containing protein ( VCP ) gene in an Italian family with autosomal dominantly inherited amyotrophic lateral sclerosis (ALS). Mutations in VCP have previously been identified in families with Inclusion Body Myopathy, Paget disease, and Frontotemporal Dementia (IBMPFD). Screening of VCP in a cohort of 210 familial ALS cases and 78 autopsy-proven ALS cases identified four additional mutations including a p.R155H mutation in a pathologically proven case of ALS. VCP protein is essential for maturation of ubiquitin-containing autophagosomes, and mutant VCP toxicity is partially mediated through its effect on…