Delving into the Latest Updates on AAV9-HEXA/HEXB gene therapy (Axovant Sciences) with Synapse

Overview

Basic Info

Drug Type

AAV based gene therapy

Synonyms-

Target

Mechanism

HEXA modulators(hexosaminidase subunit alpha modulators), HEXB modulators(hexosaminidase subunit beta modulators), Gene transference

Therapeutic Areas

Nervous System DiseasesCongenital DisordersEndocrinology and Metabolic Disease+ [1]

Active Indication

Tay-Sachs DiseaseSandhoff Disease

Inactive Indication-

Originator Organization

UMass Chan Medical School

Active Organization

UMass Chan Medical School

Sio Gene Therapies, Inc.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

G(M2) gangliosidoses are severe neurodegenerative disorders resulting from a deficiency in β-hexosaminidase A activity and lacking effective therapies. Using a Sandhoff disease (SD) mouse model (Hexb(-/-)) of the G(M2) gangliosidoses, we tested the potential of systemically delivered adeno-associated virus 9 (AAV9) expressing Hexb cDNA to correct the neurological phenotype. Neonatal or adult SD and normal mice were intravenously injected with AAV9-HexB or -LacZ and monitored for serum β-hexosaminidase activity, motor function, and survival. Brain G(M2) ganglioside, β-hexosaminidase activity, and inflammation were assessed at experimental week 43, or an earlier humane end point. SD mice injected with AAV9-LacZ died by 17 weeks of age, whereas all neonatal AAV9-HexB-treated SD mice survived until 43 weeks (P < 0.0001) with only three exhibiting neurological dysfunction. SD mice treated as adults with AAV9-HexB died between 17 and 35 weeks. Neonatal SD-HexB-treated mice had a significant increase in brain β-hexosaminidase activity, and a reduction in G(M2) ganglioside storage and neuroinflammation compared to adult SD-HexB- and SD-LacZ-treated groups. However, at 43 weeks, 8 of 10 neonatal-HexB injected control and SD mice exhibited liver or lung tumors. This study demonstrates the potential for long-term correction of SD and other G(M2) gangliosidoses through early rAAV9 based systemic gene therapy.

100 Deals associated with AAV9-HEXA/HEXB gene therapy (Axovant Sciences)

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