Delving into the Latest Updates on AAVrh.10hAPOE2-HA with Synapse

Overview

Basic Info

Drug Type

AAV based gene therapy

Synonyms

AAVrh.10hPOE2

Target

ApoE2

Mechanism

ApoE2 modulators(Apolipoprotein E2 modulators)

Therapeutic Areas

Nervous System Diseases

Active Indication-

Inactive Indication

Alzheimer Disease

Originator Organization

Weill Medical College of Cornell University

Active Organization-

Inactive Organization

Weill Medical College of Cornell University

Drug Highest PhasePendingPhase 1

First Approval Date-

Regulation-

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Author: Pey, Eduard ; Monette, Sebastien ; Chen, Alvin ; De, Bishnu P. ; Petsko, Gregory A. ; Kaplitt, Michael G. ; Flagiello, Thomas ; Zhao, Lingzhi ; Paul, Steven M. ; Ricart Arbona, Rodolfo J. ; Rosenberg, Jonathan B. ; Crystal, Ronald G. ; Dyke, Jonathan P. ; Kaminsky, Stephen M. ; Sondhi, Dolan ; Salami, Christiana ; Ballon, Douglas J.

Alzheimer's disease (AD) is a progressive degenerative neurological disorder affecting nearly one in nine elderly people in the United States. Population studies have shown that an inheritance of the apolipoprotein E (APOE) variant APOE4 allele increases the risk of developing AD, whereas APOE2 homozygotes are protected from late-onset AD. It was hypothesized that expression of the "protective" APOE2 variant by genetic modification of the central nervous system (CNS) of APOE4 homozygotes could reverse or prevent progressive neurologic damage. To assess the CNS distribution and safety of APOE2 gene therapy for AD in a large-animal model, intraparenchymal, intracisternal, and intraventricular routes of delivery to the CNS of nonhuman primates of AAVrh.10hAPOE2-HA, an AAVrh.10 serotype coding for an HA-tagged human APOE2 cDNA sequence, were evaluated. To evaluate the route of delivery that achieves the widest extent of APOE2 expression in the CNS, the expression of APOE2 in the CNS was evaluated 2 months following vector administration for APOE2 DNA, mRNA, and protein. Finally, using conventional toxicology assays, the safety of the best route of delivery was assessed. The data demonstrated that while all three routes are capable of mediating ApoE2 expression in AD relevant regions, intracisternal delivery of AAVrh.10hAPOE2-HA safely mediated wide distribution of ApoE2 with the least invasive surgical intervention, thus providing the optimal strategy to deliver vector-mediated human APOE2 to the CNS.

100 Deals associated with AAVrh.10hAPOE2-HA

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