MLD |
Mice |
AAV 9 |
IV |
2 × 1012
|
Improvement in behavior, biochemistry |
Miyaki et al2626 Miyake, N, Miyake, K, Asakawa, N, Yamamoto, M, Shimada, T. Long-term correction of biochemical and neurological abnormalities in MLD mice model by neonatal systemic injection of an AAV serotype 9 vector. Gene Ther. 2014;21(4):427–433. doi:10.1038/gt.2014.17. https://doi.org/10.1038/gt.2014.17...
|
Krabbe disease |
Mice |
AAV 2/5 |
Intracranial |
2.4 × 109
|
Improvements in biochemistry and histology; neurobehavioral performance and prolonged life span |
Lin et al2727 Lin, DS, Hsiao, CD, Lee, AYL. Mitigation of cerebellar neuropathy in globoid cell leukodystrophy mice by AAV-mediated gene therapy. Gene. 2015;571(1):81–90. doi:10.1016/j.gene.2015.06.049. https://doi.org/10.1016/j.gene.2015.06.0...
|
MPS VII |
Canine |
AAV 9 or rh10 |
IV and/or IT |
2 × 1013 or 5 × 1012
|
Biochemical improvements. IT injection is more effective than IV injection |
Gurda et al2222 Gurda, BL, De Guilhem De Lataillade, A, Bell, P. Evaluation of AAV-mediated gene therapy for central nervous system disease in canine mucopolysaccharidosis VII. Mol Ther. 2016;24(2):206–216. doi:10.1038/mt.2015.189. https://doi.org/10.1038/mt.2015.189...
|
GM1-gangliosidosis |
Mice |
AAV 9 |
IV |
1 × 1011 or 3 × 1011
|
Improvements performance in motor function and behavior, enzyme, and GAG clearance |
Weismann et al2323 Weismann, CM, Ferreira, J, Keeler, AM. Systemic AAV9 gene transfer in adult GM1 gangliosidosis mice reduces lysosomal storage in CNS and extends lifespan. Hum Mol Genet. 2015;24(15):4353–4364. doi:10.1093/hmg/ddv168. https://doi.org/10.1093/hmg/ddv168...
|
Sandhoff disease |
Feline |
AAV 8 |
Multiple intracranial injections |
4.5 × 1011 (Thal), 1.6 × 1011 (DCN), 6.4 × 1011 (ICV) |
GAG clearance in cerebral cortex and liver |
Gray-Edwards et al">2323 Weismann, CM, Ferreira, J, Keeler, AM. Systemic AAV9 gene transfer in adult GM1 gangliosidosis mice reduces lysosomal storage in CNS and extends lifespan. Hum Mol Genet. 2015;24(15):4353–4364. doi:10.1093/hmg/ddv168. https://doi.org/10.1093/hmg/ddv168...
|
Sandhoff disease |
Feline |
AAV 8 |
Multiple intracranial injections |
4.5 × 1011 (Thal), 1.6 × 1011 (DCN), 6.4 × 1011 (ICV) |
GAG clearance in cerebral cortex and liver |
Gray-Edwards et al2525 Gray-Edwards, HL, Brunson, BL, Holland, M. Mucopolysaccharidosis-like phenotype in feline Sandhoff disease and partial correction after AAV gene therapy. Mol Genet Metab. 2015;116(1-2):80–87. doi:10.1016/j.ymgme.2015.05.003. https://doi.org/10.1016/j.ymgme.2015.05....
|
MPS I |
Feline |
AAV 9 |
IT |
1012
|
Correction of biochemistry and histology |
Hinderer et al">2525 Gray-Edwards, HL, Brunson, BL, Holland, M. Mucopolysaccharidosis-like phenotype in feline Sandhoff disease and partial correction after AAV gene therapy. Mol Genet Metab. 2015;116(1-2):80–87. doi:10.1016/j.ymgme.2015.05.003. https://doi.org/10.1016/j.ymgme.2015.05....
|
MPS I |
Feline |
AAV 9 |
IT |
1012
|
Correction of biochemistry and histology |
Hinderer et al2828 Hinderer, C, Bell, P, Gurda, BL. Intrathecal gene therapy corrects CNS pathology in a feline model of mucopolysaccharidosis I. Mol Ther. 2014;22(12):2018–2027. doi:10.1038/mt.2014.135. https://doi.org/10.1038/mt.2014.135...
|
MPS IIIB |
Mice |
AAV 5, 8, 9, 10 |
Intracranial |
4.8 × 109
|
AAV 8, 9 represent optimal candidates for early gene therapy (biodistribution and transduction efficiency profiles) |
Gilkes et al">2828 Hinderer, C, Bell, P, Gurda, BL. Intrathecal gene therapy corrects CNS pathology in a feline model of mucopolysaccharidosis I. Mol Ther. 2014;22(12):2018–2027. doi:10.1038/mt.2014.135. https://doi.org/10.1038/mt.2014.135...
|
MPS IIIB |
Mice |
AAV 5, 8, 9, 10 |
Intracranial |
4.8 × 109
|
AAV 8, 9 represent optimal candidates for early gene therapy (biodistribution and transduction efficiency profiles) |
Gilkes et al2424 Gilkes, JA, Bloom, MD, Heldermon, CD. Preferred transduction with AAV8 and AAV9 via thalamic administration in the MPS IIIB model: a comparison of four rAAV serotypes. Mol Genet Metab Reports. 2016;6:48–54. doi:10.1016/j.ymgmr.2015.11.006. https://doi.org/10.1016/j.ymgmr.2015.11....
|