Blog
About

58
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Peripheral SMN restoration is essential for long-term rescue of a severe SMA mouse model

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Related collections

          Most cited references 30

          • Record: found
          • Abstract: found
          • Article: not found

          Identification and characterization of a spinal muscular atrophy-determining gene.

          Spinal muscular atrophy (SMA) is a common fatal autosomal recessive disorder characterized by degeneration of lower motor neurons, leading to progressive paralysis with muscular atrophy. The gene for SMA has been mapped to chromosome 5q13, where large-scale deletions have been reported. We describe here the inverted duplication of a 500 kb element in normal chromosomes and narrow the critical region to 140 kb within the telomeric region. This interval contains a 20 kb gene encoding a novel protein of 294 amino acids. An highly homologous gene is present in the centromeric element of 95% of controls. The telomeric gene is either lacking or interrupted in 226 of 229 patients, and patients retaining this gene (3 of 229) carry either a point mutation (Y272C) or short deletions in the consensus splice sites of introns 6 and 7. These data suggest that this gene, termed the survival motor neuron (SMN) gene, is an SMA-determining gene.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The plasticity of aging: insights from long-lived mutants.

            Mutations in genes affecting endocrine signaling, stress responses, metabolism, and telomeres can all increase the life spans of model organisms. These mutations have revealed evolutionarily conserved pathways for aging, some of which appear to extend life span in response to sensory cues, caloric restriction, or stress. Many mutations affecting longevity pathways delay age-related disease, and the molecular analysis of these pathways is leading to a mechanistic understanding of how these two processes--aging and disease susceptibility--are linked.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN.

              Spinal muscular atrophy (SMA), the most common autosomal recessive neurodegenerative disease affecting children, results in impaired motor neuron function. Despite knowledge of the pathogenic role of decreased survival motor neuron (SMN) protein levels, efforts to increase SMN have not resulted in a treatment for patients. We recently demonstrated that self-complementary adeno-associated virus 9 (scAAV9) can infect approximately 60% of motor neurons when injected intravenously into neonatal mice. Here we use scAAV9-mediated postnatal day 1 vascular gene delivery to replace SMN in SMA pups and rescue motor function, neuromuscular physiology and life span. Treatment on postnatal day 5 results in partial correction, whereas postnatal day 10 treatment has little effect, suggesting a developmental period in which scAAV9 therapy has maximal benefit. Notably, we also show extensive scAAV9-mediated motor neuron transduction after injection into a newborn cynomolgus macaque. This demonstration that scAAV9 traverses the blood-brain barrier in a nonhuman primate emphasizes the clinical potential of scAAV9 gene therapy for SMA.
                Bookmark

                Author and article information

                Affiliations
                [1 ]Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, NY 11724
                [2 ]Isis Pharmaceuticals, 1896 Rutherford Road, Carlsbad, CA 92008
                Author notes
                Correspondence and requests for materials should be addressed to A.R.K. ( Krainer@ 123456cshl.edu )
                Journal
                0410462
                6011
                Nature
                Nature
                0028-0836
                1476-4687
                19 August 2011
                5 October 2011
                6 April 2012
                : 478
                : 7367
                : 123-126
                3191865
                21979052
                10.1038/nature10485
                nihpa319393

                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                Funding
                Funded by: National Institute of General Medical Sciences : NIGMS
                Award ID: R01 GM042699-21 || GM
                Categories
                Article

                Uncategorized

                Comments

                Comment on this article