Complete Correction of Brain and Spinal Cord Pathology in Metachromatic Leukodystrophy Mice

被引:12
作者
Audouard, Emilie [1 ]
Oger, Valentin [1 ]
Meha, Beatrix [1 ]
Cartier, Nathalie [1 ]
Sevin, Caroline [1 ,2 ]
Piguet, Francoise [1 ]
机构
[1] Sorbonne Univ, ICM, Inst Cerveau & Moelle Epiniere, CNRS,UMR 7225,INSERM,U 1127, Paris, France
[2] Bicetre Hosp, Neuropediat Unit, Paris, France
关键词
metachromatic leukodystrophy; aav; gene therapy; intravenous injection (i; v; sulfatide accumulation; lysosomal storage disease; INTRACEREBRAL GENE-THERAPY; A-DEFICIENT MICE; ADENOASSOCIATED VIRUS; MOUSE MODEL; ARYLSULFATASE; CHILDREN; SULFATIDE; DISEASE; VECTOR; FORMS;
D O I
10.3389/fnmol.2021.677895
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder characterized by accumulation of sulfatides in both glial cells and neurons. MLD results from an inherited deficiency of arylsulfatase A (ARSA) and myelin degeneration in the central and peripheral nervous systems. Currently, no effective treatment is available for the most frequent late infantile (LI) form of MLD after symptom onset. The LI form results in rapid neurological degradation and early death. ARSA enzyme must be rapidly and efficiently delivered to brain and spinal cord oligodendrocytes of patients with LI MLD in order to potentially stop the progression of the disease. We previously showed that brain gene therapy with adeno-associated virus serotype rh10 (AAVrh10) driving the expression of human ARSA cDNA alleviated most long-term disease manifestations in MLD mice but was not sufficient in MLD patient to improve disease progression. Herein, we evaluated the short-term effects of intravenous AAVPHP.eB delivery driving the expression of human ARSA cDNA under the control of the cytomegalovirus/b-actin hybrid (CAG) promoter in 6-month-old MLD mice that already show marked sulfatide accumulation and brain pathology. Within 3 months, a single intravenous injection of AAVPHP.eB-hARSA-HA resulted in correction of brain and spinal cord sulfatide storage, and improvement of astrogliosis and microgliosis in brain and spinal cord of treated animals. These results strongly support to consider the use of AAVPHP.eB-hARSA vector for intravenous gene therapy in symptomatic rapidly progressing forms of MLD.
引用
收藏
页数:12
相关论文
共 35 条
[1]   A PEDIGREE STUDY OF METACHROMATIC LEUKODYSTROPHY . BIOCHEMICAL IDENTIFICATION OF CARRIER STATE [J].
BASS, NH ;
WITMER, EJ ;
DREIFUSS, FE .
NEUROLOGY, 1970, 20 (01) :52-&
[2]   Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy [J].
Biffi, Alessandra ;
Montini, Eugenio ;
Lorioli, Laura ;
Cesani, Martina ;
Fumagalli, Francesca ;
Plati, Tiziana ;
Baldoli, Cristina ;
Martino, Sabata ;
Calabria, Andrea ;
Canale, Sabrina ;
Benedicenti, Fabrizio ;
Vallanti, Giuliana ;
Biasco, Luca ;
Leo, Simone ;
Kabbara, Nabil ;
Zanetti, Gianluigi ;
Rizzo, William B. ;
Mehta, Nalini A. L. ;
Cicalese, Maria Pia ;
Casiraghi, Miriam ;
Boelens, Jaap J. ;
Del Carro, Ubaldo ;
Dow, David J. ;
Schmidt, Manfred ;
Assanelli, Andrea ;
Neduva, Victor ;
Di Serio, Clelia ;
Stupka, Elia ;
Gardner, Jason ;
von Kalle, Christof ;
Bordignon, Claudio ;
Ciceri, Fabio ;
Rovelli, Attilio ;
Roncarolo, Maria Grazia ;
Aiuti, Alessandro ;
Sessa, Maria ;
Naldini, Luigi .
SCIENCE, 2013, 341 (6148) :864-U58
[3]   Long-term outcomes after allogeneic hematopoietic stem cell transplantation for metachromatic leukodystrophy: the largest single-institution cohort report [J].
Boucher, Alexander A. ;
Miller, Weston ;
Shanley, Ryan ;
Ziegler, Richard ;
Lund, Troy ;
Raymond, Gerald ;
Orchard, Paul J. .
ORPHANET JOURNAL OF RARE DISEASES, 2015, 10
[4]   Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems [J].
Chan, Ken Y. ;
Jang, Min J. ;
Yoo, Bryan B. ;
Greenbaum, Alon ;
Ravi, Namita ;
Wu, Wei-Li ;
Sanchez-Guardado, Luis ;
Lois, Carlos ;
Mazmanian, Sarkis K. ;
Deverman, Benjamin E. ;
Gradinaru, Viviana .
NATURE NEUROSCIENCE, 2017, 20 (08) :1172-+
[5]   Efficient intracerebral delivery of AAV5 vector encoding human ARSA in non-human primate [J].
Colle, Marie-Anne ;
Piguet, Francoise ;
Bertrand, Lise ;
Raoul, Sylvie ;
Bieche, Ivan ;
Dubreil, Laurence ;
Sloothaak, Didi ;
Bouquet, Celine ;
Moullier, Philippe ;
Aubourg, Patrick ;
Cherel, Yan ;
Cartier, Nathalie ;
Sevin, Caroline .
HUMAN MOLECULAR GENETICS, 2010, 19 (01) :147-158
[6]   Safety of intrathecal delivery of recombinant human arylsulfatase A in children with metachromatic leukodystrophy: Results from a phase 1/2 clinical trial [J].
Dali, Christine, I ;
Sevin, Caroline ;
Kraegeloh-Mann, Ingeborg ;
Giugliani, Roberto ;
Sakai, Norio ;
Wu, James ;
Wasilewski, Margaret .
MOLECULAR GENETICS AND METABOLISM, 2020, 131 (1-2) :235-244
[7]   Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain [J].
Deverman, Benjamin E. ;
Pravdo, Piers L. ;
Simpson, Bryan P. ;
Kumar, Sripriya Ravindra ;
Chan, Ken Y. ;
Banerjee, Abhik ;
Wu, Wei-Li ;
Yang, Bin ;
Huber, Nina ;
Pasca, Sergiu P. ;
Gradinaru, Viviana .
NATURE BIOTECHNOLOGY, 2016, 34 (02) :204-+
[8]   Differential Prevalence of Antibodies Against Adeno-Associated Virus in Healthy Children and Patients with Mucopolysaccharidosis III: Perspective for AAV-Mediated Gene Therapy [J].
Fu, Haiyan ;
Meadows, Aaron S. ;
Pineda, Ricardo J. ;
Kunkler, Krista L. ;
Truxal, Kristen V. ;
McBride, Kim L. ;
Flanigan, Kevin M. ;
McCarty, Douglas M. .
HUMAN GENE THERAPY CLINICAL DEVELOPMENT, 2017, 28 (04) :187-196
[9]   Metachromatic Leukodystrophy - An Update [J].
Gieselmann, V. ;
Kraegeloh-Mann, I. .
NEUROPEDIATRICS, 2010, 41 (01) :1-6
[10]  
Gieselmann V., 2006, Scriver's Online Metabolic and Molecular Bases of Inherited Disease, DOI [10.1036/ommbid.179, DOI 10.1036/OMMBID.179]