Last update 21 Nov 2024

AAV2/8-TYMP gene therapy (Universitat Autonoma de Barcelona/Columbia University)

Last update 21 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

AAV based gene therapy

Synonyms-

Target

TYMP

Mechanism

TYMP stimulants(Thymidine phosphorylase stimulants)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic DiseaseSkin and Musculoskeletal Diseases+ [1]

Active Indication

Mitochondrial Encephalomyopathies

Inactive Indication-

Originator Organization

Universitat Autònoma de Barcelona

Active Organization

Columbia University Medical CenterUniversitat Autònoma de Barcelona

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

100 Clinical Results associated with AAV2/8-TYMP gene therapy (Universitat Autonoma de Barcelona/Columbia University)

100 Translational Medicine associated with AAV2/8-TYMP gene therapy (Universitat Autonoma de Barcelona/Columbia University)

100 Patents (Medical) associated with AAV2/8-TYMP gene therapy (Universitat Autonoma de Barcelona/Columbia University)

Literatures (Medical) associated with AAV2/8-TYMP gene therapy (Universitat Autonoma de Barcelona/Columbia University)

01 May 2022·Human Gene TherapyQ2 · MEDICINE

Minimum Effective Dose to Achieve Biochemical Correction with Adeno-Associated Virus Vector-Mediated Gene Therapy in Mice with Pompe Disease

Q2 · MEDICINE

Article

Author: Koeberl, Dwight ; Gheorghiu, Dorothy ; Han, Sang-Oh ; Kang, Hye Ri ; Li, Songtao

Pompe disease is an autosomal recessive lysosomal storage disorder caused by deficiency of acid α-glucosidase (GAA), resulting in skeletal muscle weakness and cardiomyopathy. Muscle weakness progresses despite currently available therapy, which has prompted the development of gene therapy with adeno-associated virus (AAV) type 2 vectors cross-packaged as AAV8 (2/8). Preclinical studies of gene therapy demonstrated that the minimum effective dose (MED) for biochemical correction with AAV2/8-LSPhGAA was ∼2 × 10¹¹ vector genomes (vg)/kg body weight. The current study examined the transduction of AAV2/8-LSPeGFP vector in adult GAA-KO mice with Pompe disease, and correlated that degree of transduction with the biochemical correction achieved by the same dose of AAV2/8-LSPhGAA. The MED was found to be ∼2 × 10¹¹ vg/kg, with all hepatocytes variably transducing at this dose. At this dose, liver GAA significantly increased, while liver glycogen significantly decreased. The 2 × 10¹¹ vg/kg dose was sufficient to significantly decrease diaphragm glycogen. However, the heart, diaphragm, and quadriceps all required a fourfold higher dose to achieve correction of GAA deficiency in association with significant clearance of stored glycogen, which correlated with increased serum GAA activity. These data indicate that AAV2/8-LSPeGFP transduced all hepatocytes when the 2 × 10¹¹ vg/kg dose was administered, which correlated with partial biochemical correction from the equivalent dose of AAV2/8-LSPhGAA. Altogether, these data support the conclusion that substantial transduction of the liver is required to achieve biochemical correction from AAV2/8-LSPhGAA.

01 Aug 2016·Human Gene TherapyQ2 · MEDICINE

Liver-Specific Allergen Gene Transfer by Adeno-Associated Virus Suppresses Allergic Airway Inflammation in Mice

Q2 · MEDICINE

Article

Author: Chen, Li-Chen ; Wu, Chia-Jen ; Lai, Chin-Wen ; Kuo, Ming-Ling ; Chan, Cheng-Chi ; Tao, Mi-Hua

Allergic airway inflammation driven by T helper 2 (Th2)-type immunity is characterized by airway hyperresponsiveness, eosinophilic infiltration, and elevated IgE production. Various novel strategies for managing asthma have been explored, such as DNA vaccines, T-cell peptides, and allergen-specific immunotherapy. A principal goal of most immunotherapeutic approaches is active and long-term allergen-specific tolerance. Liver-specific gene transfer using adeno-associated virus (AAV) has been shown to favorably induce tolerogenic responses to therapeutic products in various experimental models. AAV8 has strong liver tropism and induces immune tolerance in mice. The present study aimed to determine whether hepatocyte-specific allergen expression by pseudotyped AAV2/8 alleviates asthmatic symptoms in ovalbumin (OVA)-sensitized mice. Mice were intravenously injected with AAV2/8 vector carrying membrane-bound OVA transgene under transcriptional control of a hepatocyte-specific alpha 1 antitrypsin promoter (AAV2/8-OVA) and then sensitized with OVA. AAV2/8-OVA specifically transduced the OVA transgene in the liver. Airway hyperresponsiveness, eosinophilia, mucus hypersecretion, and Th2 cytokines were significantly suppressed in both the lungs and secondary lymphoid organs of asthmatic mice infected with AAV2/8-OVA. Significant reduction of OVA-specific antibodies was detected in the bronchoalveolar lavage fluid from AAV2/8-OVA-treated mice. Moreover, AAV2/8-OVA treatment prominently promoted the expression of Foxp3, IL-10, and TGF-β in the liver. Enhanced Foxp3 expression was also detected in the lungs of asthmatic mice after AAV2/8-OVA treatment. Taken together, these results suggest that the induction of immune tolerance by hepatic AAV gene transfer may be beneficial for modulating allergic asthma.

01 Mar 2010·Molecular TherapyQ1 · MEDICINE

Differential Transduction Following Basal Ganglia Administration of Distinct Pseudotyped AAV Capsid Serotypes in Nonhuman Primates

Q1 · MEDICINE

Article

Author: Tomas Bjorklund ; Ronald J Mandel ; Deniz Kirik ; James Stansell ; Jeffrey H Kordower ; Hemraj B Dodiya

We examined the transduction efficiency of different adeno-associated virus (AAV) capsid serotypes encoding for green fluorescent protein (GFP) flanked by AAV2 inverted terminal repeats in the nonhuman primate basal ganglia as a prelude to translational studies, as well as clinical trials in patients with Parkinson's disease (PD). Six intact young adult cynomolgus monkeys received a single 10 microl injection of AAV2/1-GFP, AAV2/5-GFP, or AAV2/8-GFP pseudotyped vectors into the caudate nucleus and putamen bilaterally in a pattern that resulted in each capsid serotype being injected into at least four striatal sites. GFP immunohistochemistry revealed excellent transduction rates for each AAV pseudotype. Stereological estimates of GFP+ cells within the striatum revealed that AAV2/5-GFP transduces significantly higher number of cells than AAV2/8-GFP (P < 0.05) and there was no significant difference between AAV2/5-GFP and AAV2/1-GFP (P = 0.348). Consistent with this result, Cavalieri estimates revealed that AAV2/5-GFP resulted in a significantly larger transduction volume than AAV2/8-GFP (P < 0.05). Each pseudotype transduced striatal neurons effectively [>95% GFP+ cells colocalized neuron-specific nuclear protein (NeuN)]. The current data suggest that AAV2/5 and AAV2/1 are superior to AAV2/8 for gene delivery to the nonhuman primate striatum and therefore better candidates for therapeutic applications targeting this structure.

100 Deals associated with AAV2/8-TYMP gene therapy (Universitat Autonoma de Barcelona/Columbia University)

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Mitochondrial Encephalomyopathies	Preclinical	ES	Universitat Autònoma de Barcelona	-
Mitochondrial Encephalomyopathies	Preclinical	US	Columbia University Medical Center	-

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AAV2/8-TYMP gene therapy (Universitat Autonoma de Barcelona/Columbia University)

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Translational Medicine

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