Current Gene Therapy

Ignacio Anegon
Director INSERM UMR 1064-Center for Research in Transplantation and Immunology
CHU de Nantes. 30, boulevard
Nantes
France

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Symptomatic Improvement, Increased Life-Span and Sustained Cell Homing in Amyotrophic Lateral Sclerosis After Transplantation of Human Umbilical Cord Blood Cells Genetically Modified with Adeno-Viral Vectors Expressing a Neuro-Protective Factor and a Neural Cell Adhesion Molecule

Author(s): Rustem Robertovich Islamov, Albert Anatolyevich Rizvanov, Marat Alexandrovich Mukhamedyarov, Ilnur Ildusovich Salafutdinov, Ekaterina Evgenevna Garanina, Valeria Yuryevna Fedotova, Valeria Vladimirovna Solovyeva, Yana Olegovna Mukhamedshina, Zufar Zufarovich Safiullov, Andrey Alexandrovich Izmailov, Daria Sergeevna Guseva, Andrey Lvovich Zefirov, Andrey Pavlovich Kiyasov, Andras Palotas.

Abstract:

Amyotrophic lateral sclerosis (ALS) is an incurable, chronic, fatal neuro-degenerative disease characterized by progressive loss of moto-neurons and paralysis of skeletal muscles. Reactivating dysfunctional areas is under earnest investigation utilizing various approaches. Here we present an innovative gene-cell construct aimed at reviving inert structure and function. Human umbilical cord blood cells (hUCBCs) transduced with adeno-viral vectors encoding human VEGF, GDNF and/or NCAM genes were transplanted into transgenic ALS mice models. Significant improvement in behavioral performance (open-field and grip-strength tests), as well as increased life-span was observed in rodents treated with NCAM-VEGF or NCAM-GDNF co-transfected cells. Active trans-gene expression was found in the spinal cord of ALS mice 10 weeks after delivering genetically modified hUCBCs, and cells were detectable even 5 months following transplantation. Our gene-cell therapy model yielded prominent symptomatic control and prolonged life-time in ALS. Incredible survivability of xeno-transpanted cells was also observed without any immune-suppression. These results suggest that engineered hUCBCs may offer effective gene-cell therapy in ALS.

Keywords: Adeno-virus, amyotrophic lateral sclerosis (ALS), gene-cell therapy, glial cell-derived neuro-trophic factor (GDNF), human umbilical cord blood cell (hUCBC), human umbilical cord blood mono-nuclear cell (hUCB-MC), neural cell adhesion molecule (NCAM), vascular endothelial growth factor (VEGF), viral vector.

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Article Details

VOLUME: 15
ISSUE: 3
Year: 2015
Page: [266 - 276]
Pages: 11
DOI: 10.2174/1566523215666150126122317
Price: $58