CRIM-negative Pompe disease patients with satisfactory clinical outcomes on enzyme replacement therapy

Khallaf, Hamoud Al; Propst, Jennifer; Botha, Eleanor G.; Pervaiz, Muhammad Khalid

doi:10.1016/j.ymgme.2012.11.018

Cited by 6 publications

(5 citation statements)

References 16 publications

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“…This is consistent with a previous study that compared the level of antibody titers between patients treated with 20 or 40 mg/kg eow (Banugaria et al 2011). In line with previous observations (Khallaf et al 2013; van Gelder et al 2014) the patient's peak antibody titer seemed to be related to the age at start of therapy.…”

Section: Discussionmentioning

confidence: 99%

Effects of a higher dose of alglucosidase alfa on ventilator‐free survival and motor outcome in classic infantile Pompe disease: an open‐label single‐center study

Gelder

Poelman

Plug

et al. 2016

J of Inher Metab Disea

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BackgroundThough enzyme-replacement therapy (ERT) with alglucosidase alfa has significantly improved the prospects for patients with classic infantile Pompe disease, some 50 % of treated infants do not survive ventilator-free beyond the age of 3 years. We investigated whether higher and more frequent dosing of alglucosidase alfa improves outcome.MethodsEight cross-reactive immunological material (CRIM) positive patients were included in the study. All had fully deleterious mutations in both GAA alleles. Four received a dose of 20 mg/kg every other week (eow) and four received 40 mg/kg/week. Survival, ventilator-free survival, left-ventricular mass index (LVMI), motor outcome, infusion-associated reactions (IARs), and antibody formation were evaluated.ResultsAll eight patients were alive at study end, seven of them remained ventilator-free. The patient who became ventilator dependent was treated with 20 mg/kg eow. Three of the four patients receiving 20 mg/kg eow learned to walk; two of them maintained this ability at study end. All four patients receiving 40 mg/kg/week acquired and maintained the ability to walk at study end (ages of 3.3–5.6 years), even though their baseline motor functioning was poorer. There were no apparent differences between the two dose groups with respect to the effect of ERT on LVMI, the number of IARs and antibody formation.ConclusionsOur data may suggest that a dose of 40 mg/kg/week improves outcome of CRIM positive patients over that brought by the currently recommended dose of 20 mg/kg eow. Larger studies are needed to draw definite conclusions.

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Section: Discussionmentioning

confidence: 99%

Effects of a higher dose of alglucosidase alfa on ventilator‐free survival and motor outcome in classic infantile Pompe disease: an open‐label single‐center study

Gelder

Poelman

Plug

et al. 2016

J of Inher Metab Disea

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“…El curso clínico de la enfermedad ha cambiado con el advenimiento de la terapia de reemplazo enzimático con alglucosidasa alfa. 7 El diagnóstico clínico es confirmado por la ausencia o reducción acentuada de la actividad de la alfa-glucosidasa ácida. 7 Todos los pacientes tenían baja actividad enzimática de alfa-glucosidasa ácida; posteriormente, el análisis molecular confirmó el diagnóstico.…”

Section: Discussionunclassified

“…7 El diagnóstico clínico es confirmado por la ausencia o reducción acentuada de la actividad de la alfa-glucosidasa ácida. 7 Todos los pacientes tenían baja actividad enzimática de alfa-glucosidasa ácida; posteriormente, el análisis molecular confirmó el diagnóstico. Ningún paciente requirió biopsia de músculo para establecer el diagnóstico, ya que el estudio en gota de sangre seca es rápido, sencillo y no invasivo.…”

Section: Discussionunclassified

Infantile-onset Pompe disease in seven Mexican children

Sánchez‐Sánchez

Ávila-Rejón

Díaz-Martínez

et al. 2022

GMM

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Introducción: La enfermedad de Pompe (EP) es una forma rara de miopatía metabólica; la presentación infantil clásica es severa y el fallecimiento acontece antes del año de vida, y la forma no clásica es de progresión más lenta y la sobrevivencia puede superar el año. Objetivo: Describir genotipo y características de pacientes mexicanos con EP de inicio infantil. Métodos: Se incluyeron siete pacientes con enfermedad confirmada mediante actividad enzimática y estudio molecular del gen GAA. Se revisaron las mutaciones en bases de datos genómicas. Resultados: La mediana de la edad de inicio de los síntomas fue de cuatro meses (1-12 meses) y la edad de diagnóstico fue de ocho meses (4-16 meses). Todos los pacientes tenían cardiomiopatía: cuatro que fallecieron antes del año presentaron mutaciones que predicen enfermedad severa (c.2431dup, c.2560C>T, c.655G>A, c.1987delC) y CRIM (cross-reactive immunologic material) negativo; tres sobrevivieron después del año de edad con terapia de reemplazo enzimático, uno casi cinco años, otro 18 meses y una niña tenía casi tres años al momento de este informe; sus variantes patogénicas predecían enfermedad potencialmente menos severa (c.1979G>A, c.655G>A, c.1447G>A) y CRIM positivo. Conclusión: Existió buena correlación entre genotipo y fenotipo en niños con enfermedad de Pompe.

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“…Currently, there is no effective treatment or cure for people living with PD. Sanofi-Genzyme, Inc. using a rhGAA (alglucosidase alfa) secreted from a CHO cell line has demonstrated moderate success in patients (27), however yearly costs are very high. Although alglucosidase alfa has been a wonderful first step in treating PD it has revealed subtle aspects that must be dealt with for successful treatment (18,(42)(43)(44)(45)(46)(47)(48)(49).…”

Section: Discussionmentioning

confidence: 99%

Preclinical studies for plant-based oral enzyme replacement therapy (Oral-ERT) in Pompe disease knockout mice with transgenic tobacco seeds expressing human GAA (tobrhGAA)

Martiniuk

Mack

Martiniuk

et al. 2021

Preprint

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Genetic deficiency of acid α-glucosidase (GAA) results in glycogen storage disease type II (GSDII) or Pompe disease (PD) encompassing at least four clinical subtypes of varying severity (infantile; childhood, juvenile and late onset). Our objective is to develop an innovative and affordable approach for enzyme replacement therapy (ERT) via oral administration (Oral-ERT) to maintain a sustained, therapeutic level of enzyme on a daily basis to improve efficacy of treatment and quality of life for people living with Pompe disease. A consensus at a 2019 US Acid Maltase Deficiency (AMDA) conference suggested that a multi-pronged approach including gene therapy, diet, exercise, etc. must be evaluated for a successful treatment of Pompe disease. Tobacco seeds contain the metabolic machinery that is more compatible with mammalian glycosylation-phosphorylation and processing. Previously, we have shown that a lysate from transgenic tobacco seeds expressing human GAA (tobrhGAA) was enzymatically active and can correct enzyme deficiency in cultured PD cells and in adult lymphocytes of Pompe patients and in vivo in disease-relevant tissues in GAA knockout (KO) mice when administered IP.We have extended these pre-clinical studies in PD knockout (KO) mice with ground tobrhGAA seeds that supports proof-of-concept for Oral-ERT for future clinical trials. Briefly in GAA KO mice, Oral-ERT with ground tobrhGAA seeds showed significant reversal of fore-limb and hind-limb muscle weakness, increased motor coordination/balance/strength and mobility, improved spontaneous learning, increased GAA baseline activity in tissues, reduced glycogen in tissues and negible serum titers to GAA. Pharmacokinetics showed maximum serum GAA concentration (Cs) at 8-10 hr and peak urine excretion at 10-12 hr. The tobrhGAA was taken up in PD fibroblast, lymphoid and myoblast cells. Enzyme kinetics compared favorably or superior to placental hGAA, plus alglucosidase alfa or other rhGAAs for Km, Vmax, pH optima, thermal heat stability and IC50 for inhibitors. The tobrhGAA in seeds was extremely stable stored for 15 years at room temperature. NGS-genome sequencing of the tobrhGAA and wild-type plants and RNA expression profiles was performed and will be posted on our website. Thus, Oral-ERT with ground tobrhGAA seeds is an innovative approach that overcomes some of the challenges of alglucosidase alfa-ERT and provides a more effective, safe and significantly less expensive treatment.

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CRIM-negative Pompe disease patients with satisfactory clinical outcomes on enzyme replacement therapy

Cited by 6 publications

References 16 publications

Effects of a higher dose of alglucosidase alfa on ventilator‐free survival and motor outcome in classic infantile Pompe disease: an open‐label single‐center study

Effects of a higher dose of alglucosidase alfa on ventilator‐free survival and motor outcome in classic infantile Pompe disease: an open‐label single‐center study

Infantile-onset Pompe disease in seven Mexican children

Preclinical studies for plant-based oral enzyme replacement therapy (Oral-ERT) in Pompe disease knockout mice with transgenic tobacco seeds expressing human GAA (tobrhGAA)

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