Preclinical Evaluation of a Modified Herpes Simplex Virus Type 1 Vector Encoding Human TGM1 for the Treatment of Autosomal Recessive Congenital Ichthyosis

Freedman, John C.; Parry, Trevor J.; Zhang, PeiPei; Majumdar, Avijit; Krishnan, Suma; Regula, Lauren K.; O’Malley, Michael J.; Coghlan, Sarah; Yogesha, Sollepura D; Ramasamy, Sureshkumar; Agarwal, Pooja

doi:10.1016/j.jid.2020.07.035

Cited by 19 publications

(9 citation statements)

References 13 publications

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“…Preclinical studies have shown that the vector effectively infects TGM1-deficient human skin cells, restores the TGase-1 enzyme activity in vitro, and also significantly increases the expression of TGase-1 without toxicity when administered locally into immunocompetent BALB/c mice in vivo. It has also been described that the vector did not show toxicity and immunogenicity, even when injected weekly into the epidermis of animals, and does not spread to other areas from the injection site [ 100 ]. A phase I/II clinical trial has been recently registered (August 2019) to evaluate the safety of topical administration of this genetic vector.…”

Section: Gene Therapymentioning

confidence: 99%

Current Strategies for the Gene Therapy of Autosomal Recessive Congenital Ichthyosis and Other Types of Inherited Ichthyosis

Chulpanova

Shaimardanova

Ponomarev

et al. 2022

IJMS

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Mutations in genes such as transglutaminase-1 (TGM1), which are responsible for the formation and normal functioning of a lipid barrier, lead to the development of autosomal recessive congenital ichthyosis (ARCI). ARCIs are characterized by varying degrees of hyperkeratosis and the presence of scales on the body surface since birth. The quality of life of patients is often significantly affected, and in order to alleviate the manifestations of the disease, symptomatic therapy with moisturizers, keratolytics, retinoids and other cosmetic substances is often used to improve the condition of the patients’ skin. Graft transplantation is commonly used to correct defects of the eye. However, these approaches offer symptomatic treatment that does not restore the lost protein function or provide a long-term skin barrier. Gene and cell therapies are evolving as promising therapy for ARCIs that can correct the functional activity of altered proteins. However, these approaches are still at an early stage of development. This review discusses current studies of gene and cell therapy approaches for various types of ichthyosis and their further prospects for patient treatment.

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Section: Gene Therapymentioning

confidence: 99%

Current Strategies for the Gene Therapy of Autosomal Recessive Congenital Ichthyosis and Other Types of Inherited Ichthyosis

Chulpanova

Shaimardanova

Ponomarev

et al. 2022

IJMS

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“…[ 102 ] Original research LI Gene therapy; TGM1 in a retroviral vector 2021 Freedman et al . [ 103 ] Original research ARCI ( TGM1 ) Gene therapy; TGM1 in HSV-1 2019 March et al . [ 101 ] Original research EI ( KRT10 ) Gene therapy; TALEN 2022 Dang et al [ 105 ] Original research LI Gene therapy: base editing 2020 Lee et al .…”

Section: Introductionmentioning

confidence: 99%

New developments in the molecular treatment of ichthyosis: review of the literature

Joosten

Clabbers

Jonca

et al. 2022

Orphanet J Rare Dis

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Ichthyosis covers a wide spectrum of diseases affecting the cornification of the skin. In recent years, new advances in understanding the pathophysiology of ichthyosis have been made. This knowledge, combined with constant development of pathogenesis-based therapies, such as protein replacement therapy and gene therapy, are rather promising for patients with inherited skin diseases. Several ongoing trials are investigating the potency of these new approaches and various studies have already been published. Furthermore, a lot of case series report that biological therapeutics are effective treatment options, mainly for Netherton syndrome and autosomal recessive congenital ichthyosis. It is expected that some of these new therapies will prove their efficacy and will be incorporated in the treatment of ichthyosis.

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“…This strategy is more suitable for those skin diseases with skin lesions covering whole body, in which local skin grafts and injections have their limitations. Several topical gene therapies using modified herpes simplex virus (HSV) carrying wild‐type genes such as COL7A1 for RDEB or transglutaminase 1 ( TGM1 ) for autosomal recessive congenital ichthyosis have been developed 10,11 . The outcomes from in vivo phase 1 topical delivery gene therapy were promising and encouraging, although the expressions of therapeutic genes in the host skin/cells were transient due to non‐integrating feature of herpes simplex virus, and multiple administrations of therapeutic vector in this in vivo gene therapy are required.…”

Section: Introductionmentioning

confidence: 99%

“…Several topical gene therapies using modified herpes simplex virus (HSV) carrying wild‐type genes such as COL7A1 for RDEB or transglutaminase 1 ( TGM1 ) for autosomal recessive congenital ichthyosis have been developed. 10 , 11 The outcomes from in vivo phase 1 topical delivery gene therapy were promising and encouraging, although the expressions of therapeutic genes in the host skin/cells were transient due to non‐integrating feature of herpes simplex virus, and multiple administrations of therapeutic vector in this in vivo gene therapy are required. In addition, topically delivered vectors are difficult to target keratinocyte stem cells (KSCs) as these cells are scattered in the lowest layer of the epidermis.…”

Section: Introductionmentioning

confidence: 99%

Ex vivo gene modification therapy for genetic skin diseases—recent advances in gene modification technologies and delivery

Jayarajan¹,

Kounatidou²,

Qasim

et al. 2021

Experimental Dermatology

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Genetic skin diseases, also known as genodermatoses, are inherited disorders affecting skin and constitute a large and heterogeneous group of diseases. While genodermatoses are rare with the prevalence rate of less than 1 in 50,000 – 200,000, they frequently occur at birth or early in life and are generally chronic, severe, and could be life‐threatening. The quality of life of patients and their families are severely compromised by the negative psychosocial impact of disease, physical manifestations, and the lack or loss of autonomy. Currently, there are no curative treatments for these conditions. Ex vivo gene modification therapy that involves modification or correction of mutant genes in patients’ cells in vitro and then transplanted back to patients to restore functional gene expression has being developed for genodermatoses. In this review, the ex vivo gene modification therapy strategies for genodermatoses are reviewed, focusing on current advances in gene modification and correction in patients’ cells and delivery of genetically modified cells to patients with discussions on gene therapy trials which have been performed in this area.

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Preclinical Evaluation of a Modified Herpes Simplex Virus Type 1 Vector Encoding Human TGM1 for the Treatment of Autosomal Recessive Congenital Ichthyosis

Cited by 19 publications

References 13 publications

Current Strategies for the Gene Therapy of Autosomal Recessive Congenital Ichthyosis and Other Types of Inherited Ichthyosis

Current Strategies for the Gene Therapy of Autosomal Recessive Congenital Ichthyosis and Other Types of Inherited Ichthyosis

New developments in the molecular treatment of ichthyosis: review of the literature

Ex vivo gene modification therapy for genetic skin diseases—recent advances in gene modification technologies and delivery

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