Advances in treatment for chronic granulomatous disease

Abstract

Chronic granulomatous disease (CGD) is a rare congenital disorder resulting from a failure of neutrophils to produce oxidases. Patients are therefore prone to recurrent infections from various organisms including fungi and atypical bacteria. The mortality in patients with the X-linked form of CGD, the most common type, ranges from 3% to 5% per year and although management of infections has improved with advances in antimicrobial therapies, better methods are needed to be able to cure these patients. Peripheral blood stem cell or bone marrow transplantation, while curative, is not widely used due to the episodic nature of the infections and the belief by many that conservative management is preferable to the risks of transplantation. Still, as will be discussed, improvements in the field are making allogenic transplantation more desirable and tilting the risk benefit ratio in favor of this modality. Additionally, gene therapy, which has been a long touted method to cure CGD, has within the last 5-10 years become more and more of a reality and may be realized by the end of this decade.

PPARγ activation normalizes resolution of acute sterile inflammation in murine chronic granulomatous disease

“…48 Gene therapy for restoration of the NADPH oxidase is clearly the ultimate goal in the treatment of CGD, although the precise means of accomplishing this safely and effectively are yet to be established. 49 Importantly, transduction of even modest numbers of neutrophils is curative of immunodeficiency and may diminish inflammation as well. 50 Whether gene therapy will restore proper CGD macrophage programming is entirely unknown.…”

Successful unrelated donor cord blood transplantation for chronic granulomatous disease

“…The patients typically experience ''growth failure, inflammatory lung damage, and often early death. With X-linked and autosomal recessive forms, it has been an important disease for the development of bone marrow transplantation and gene therapy [6]. Additionally, gene-replacement therapy for patients lacking a suitable stem cell donor is still experimental and faces major obstacles and risks [7,8].…”

Terapia génica: opción terapéutica para neoplasias, infecciones y enfermedades monogénicas

“…Muchos de los ensa-yos mostraron no ser eficaces y otros se asociaron con efectos adversos inaceptables. De todos modos, resultados exitosos publicados en los úl-timos años muestran a la TG como una alternativa viable para el tratamiento de enfermedades tan disímiles como la enfermedad de Parkinson, 73 adrenoleucodistrofia, 10 enfermedad granulomatosa crónica, 18,74,75 síndrome de Wiscott Aldrich [76][77][78] y amaurosis congénita de Leber, 79,80 entre otras. Además, en el corto plazo se iniciarán ensayos clí-nicos para el tratamiento de otras importantes patologías, como la anemia de células falciformes.…”