SOD1 gene mutations in Italian patients with Sporadic Amyotrophic Lateral Sclerosis (ALS).

Mutations in the SOD1 gene exons and exon/intron boundaries were searched in 66 sporadic and 4 familial Italian ALS cases consecutively referred to our centre from different Italian regions. A mutation was found in three sporadic cases (4.5%): a new nonsense mutation in exon 5 (K136X) in a patient with a rapid and severe disease course and two previously described missense nucleotide substitutions (N65S and A95T) in two patients with a mild disease course. Comparison of the clinical characteristics with previously reported patients carrying the same or similar mutations showed a remarkable genotype-phenotype correlation. No association was found with intronic sequence variations by comparing their frequency in the patients and in 181 matched controls.

Progressive multifocal leucoencephalopathy after autologous bone marrow transplantation: a treatment option.

A patient with multiple myeloma was treated with high-dose chemotherapy followed by two autologous bone marrow transplantations (ABMTs). Nine months after the second ABMT the patient complained of severe left hemiparesis, paraesthesias, left homonymous visual field defects and gait ataxia. She was diagnosed with progressive multifocal leucoencephalopathy (PML) confirmed by detection of JC virus (JCV) DNA and prescribed cidofovir every other week and mirtazapine daily. Her symptoms and signs remained stable and after 6 months the JCV DNA was undetectable in the cerebrospinal fluid. Repeated MRI scans demonstrated the stabilisation of demyelinating lesion volume; after more than 2 years of follow-up the patient's neurological examination does not show significant variations. Combination of cidofovir and mirtazapine may be helpful in the treatment of PML in HIV-negative patients.

Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial.

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.