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Gene therapy in a murine model for clinical application to multiple sclerosis
Author(s) -
Weiner Leslie P.,
Louie Katherine A.,
Atalla Lilly R.,
Kochounian Harold H.,
Du Jing,
Wei Wenqiang,
Hinton David R.,
Gordon Erlinda M.,
Anderson W. French,
McMillan Minnie
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.10858
Subject(s) - experimental autoimmune encephalomyelitis , multiple sclerosis , medicine , genetic enhancement , immunology , antigen , cytokine , spinal cord , encephalomyelitis , cell therapy , t cell , translation (biology) , biology , cell , gene , immune system , messenger rna , biochemistry , genetics , psychiatry
Female SJL/J mice, suffering from experimental autoimmune encephalomyelitis (EAE), were injected with 1 × 10 7 cells from a syngeneic fibroblast line transduced with a retroviral vector designed to encode proteolipid protein (101‐157) targeted for secretion. A striking abrogation of both clinical and histological signs of disease resulted. The treatment was efficacious when given after the first or the third relapses, protected naive mice from challenge with spinal cord homogenate, and was dose dependent. This strategy was devised to provide a systemic, antigen‐specific signal to pathogenic T cells in the absence of costimulation and, hence, render them anergic. Cytokine analyses of brain and spinal cord lymphocytes demonstrate that the treatment induces an antiinflammatory Th2 profile, indicating that this antigen‐specific therapy acts by a cytokine‐induced pathway. This study was designed for translation to the clinic. We envision using allogeneic transduced fibroblasts, encapsulated in a chamber, to deliver the antigen‐specific signal. This will enable us to use one therapeutic cell line for all patients and to remove the device should the therapy exacerbate disease.