Success in eliminating the consequences of inherited genetic faults in a patient with butterfly skin

The Universidad Carlos III de Madrid (UC3M) has coordinated research that has successfully treated a patient with "butterfly skin" with a drug capable of eliminating the consequences of inherited mutations, for the first time. This study, carried out as part of the Chair of Regenerative Medicine and Tissue Bioengineering, involved the participation of the Centre for Energy, Environmental and Technological Research, (CIEMAT, in its Spanish acronym), the Jiménez Díaz Foundation Health Research Institute (IIS-FJD, in its Spanish acronym), the Biomedical Research Networking Center on Rare Diseases (CIBERER, in its Spanish acronym) and the Hospital Universitario La Paz (La Paz University Hospital).

Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) is a rare disorder caused by mutations in the plectin gene. In addition to having fragile skin, patients with this disease develop progressive skeletal and respiratory muscle weakness, which drastically reduces their quality of life and increases morbidity and mortality. This disease is incurable and those affected lack specific and effective treatments. This research assesses, for the first time, the use of gentamicin (an aminoglycoside) as an agent capable of suppressing the consequences of inherited mutations in a patient with EBS-MD. "This drug induces the suppression of premature termination codons caused by nonsense mutations (a specific type of mutation)," says María José Escámez, professor in the UC3M Department of Bioengineering and Aerospace Engineering and coordinator of the research team.

This work, published in JAMA Dermatology magazine, reports the efficacy of gentamicin in achieving a significant production of plectin in the patient's skin cells. "Gentamicin intravenous treatment in the patient increased plectin levels in her skin and slightly decreased skeletal and respiratory muscle weakness. Overall, it had a positive impact on quality of life," says Marcela del Río, professor in the UC3M Department of Bioengineering and Aerospace Engineering, director of the Chair and head of the CIBERER group.

This study, developed by a multidisciplinary group of researchers and clinicians, has made it possible to treat a patient with an urgent need to improve her condition. The Asociación DEBRA-Piel de Mariposa (DEBRA-Butterfly Skin Association) has also collaborated in its development.

Bibliographic reference:

Martínez-Santamaría L, Maseda R, de Arriba MDC, Membrilla JA, Sigüenza AI, Mascías J, García M, Quintana L, Esteban-Rodríguez I, Hernández-Fernández CP, Illera N, Duarte B, Guerrero-Aspizúa S, Woodley DT, Del Río M, de Lucas R, Larcher F, Escámez MJ. Evaluation of Systemic Gentamicin as Translational Readthrough Therapy for a Patient With Epidermolysis Bullosa Simplex With Muscular Dystrophy Owing to PLEC1 Pathogenic Nonsense Variants. JAMA Dermatol. 2022 Mar 2. doi: 10.1001/jamadermatol.2022.0112. Epub ahead of print. PMID: 35234827.

Bolling MC, Has C, Bruckner AL. Understanding the Potential Promise and Pitfalls of Intravenous Gentamicin as a Therapy for Epidermolysis Bullosa. JAMA Dermatol. 2022 Mar 2. doi: 10.1001/jamadermatol.2021.5630. Epub ahead of print. PMID: 35234816.