Publication Date:
2003-08-09
Description:
Amyotrophic lateral sclerosis (ALS) is a progressive, lethal neuromuscular disease that is associated with the degeneration of spinal and brainstem motor neurons, leading to atrophy of limb, axial, and respiratory muscles. The cause of ALS is unknown, and there is no effective therapy. Neurotrophic factors are candidates for therapeutic evaluation in ALS. Although chronic delivery of molecules to the central nervous system has proven difficult, we recently discovered that adeno-associated virus can be retrogradely transported efficiently from muscle to motor neurons of the spinal cord. We report that insulin-like growth factor 1 prolongs life and delays disease progression, even when delivered at the time of overt disease symptoms.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaspar, Brian K -- Llado, Jeronia -- Sherkat, Nushin -- Rothstein, Jeffrey D -- Gage, Fred H -- AG12992/AG/NIA NIH HHS/ -- AG21876/AG/NIA NIH HHS/ -- NS33958/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Aug 8;301(5634):839-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12907804" target="_blank"〉PubMed〈/a〉
Keywords:
Amyotrophic Lateral Sclerosis/pathology/physiopathology/*therapy
;
Animals
;
Apoptosis
;
Base Sequence
;
Caspase 9
;
Caspases/metabolism
;
Cell Count
;
Dependovirus/*genetics
;
Disease Models, Animal
;
Disease Progression
;
Gene Transfer Techniques
;
*Genetic Therapy
;
*Genetic Vectors/administration & dosage
;
Glial Cell Line-Derived Neurotrophic Factor
;
Green Fluorescent Proteins
;
Insulin-Like Growth Factor I/*genetics
;
Luminescent Proteins/genetics
;
Male
;
Mice
;
Mice, Transgenic
;
Molecular Sequence Data
;
Motor Neurons/pathology/virology
;
Muscle, Skeletal/virology
;
Nerve Growth Factors/genetics
;
*Protein-Serine-Threonine Kinases
;
Proto-Oncogene Proteins/metabolism
;
Proto-Oncogene Proteins c-akt
;
Random Allocation
;
Spinal Cord/chemistry/pathology/virology
;
Superoxide Dismutase/genetics/metabolism
;
Ubiquitin/analysis
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
