RESUMO
To date, more than 200 monogenic, often devastating, skin diseases have been described. Because of unmet medical needs, development of long-lasting and curative therapies has been consistently attempted, with the aim of correcting the underlying molecular defect. In this review, we will specifically address the few combined cell and gene therapy strategies that made it to the clinics. Based on these studies, what can be envisioned for the future is a patient-oriented strategy, built on the specific features of the individual in need. Most likely, a combination of different strategies, approaches, and advanced therapies will be required to reach the finish line at the end of the long and winding road hampering the achievement of definitive treatments for genodermatoses.
Assuntos
Terapia Genética/métodos , Dermatopatias/genética , Dermatopatias/terapia , Animais , Sistemas CRISPR-Cas , Epiderme/metabolismo , Epidermólise Bolhosa/terapia , Epidermólise Bolhosa Distrófica/terapia , Epidermólise Bolhosa Juncional/terapia , Genes Dominantes , Genes Recessivos , Vetores Genéticos , Humanos , Lentivirus/genética , Síndrome de Netherton/terapia , Retroviridae/genética , Simplexvirus , Pele/metabolismo , Células-Tronco/citologiaRESUMO
BACKGROUND: Netherton syndrome is a rare autosomal recessive disease demonstrating ichthyosis linearis circumflexa, atopic findings, and hair shaft anomalies. Trichorrhexis invaginata is the pathognomonic hair shaft anomaly seen in this syndrome. OBJECTIVE: In recent years, hair shaft anomalies have been described as "matchstick" and "golf tee" signs. We present a patient with Netherton syndrome diagnosed by the presence of matchstick and golf tee hairs in addition to trichorrhexis invaginata.
Assuntos
Dermoscopia , Síndrome de Netherton/patologia , Pré-Escolar , Humanos , Masculino , Síndrome de Netherton/terapiaRESUMO
Netherton syndrome (NS) is a serious inherited skin disorder caused by mutations in the serine protease inhibitor Kazal type 5 gene (SPINK5), which encodes for a serine protease inhibitor lymphoepithelial Kazal type-related inhibitor (LEKTI). Patients with NS have defective keratinization, hair shaft defects, recurrent infections, atopy, and a predisposition to skin malignancies. Historically, 1 in 10 infants has died before their first birthday. Currently, there are no proven treatments to cure this condition. A SIN-lentiviral vector encoding the codon-optimized SPINK5 gene under the control of a 572 bp element derived from the human involucrin promoter can confer compartment-specific LEKTI expression in NS keratinocytes with restoration of normal skin architecture. Here we detail a study protocol for a phase I trial for feasibility and safety evaluations of autologous epidermal sheets generated from ex vivo gene-corrected keratinocyte stem cells, which will be grafted onto patients with mutation-proven NS.