An immune tolerance approach using transient low-dose methotrexate in the ERT-naïve setting of patients treated with a therapeutic protein: experience in infantile-onset Pompe disease

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Zoheb B KaziPriya S Kishnani

Abstract

To investigate immune tolerance induction with transient low-dose methotrexate (TLD-MTX) initiated with recombinant human acid α-glucosidase (rhGAA), in treatment-naïve cross-reactive immunologic material (CRIM)-positive infantile-onset Pompe disease (IOPD) patients. Newly diagnosed IOPD patients received subcutaneous or oral 0.4 mg/kg TLD-MTX for 3 cycles (3 doses/cycle) with the first 3 rhGAA infusions. Anti-rhGAA IgG titers, classified as high-sustained (HSAT; ≥51,200, ≥2 times after 6 months), sustained intermediate (SIT; ≥12,800 and <51,200 within 12 months), or low (LT; ≤6400 within 12 months), were compared with those of 37 CRIM-positive IOPD historic comparators receiving rhGAA alone. Fourteen IOPD TLD-MTX recipients at the median age of 3.8 months (range, 0.7-13.5 months) had a median last titer of 150 (range, 0-51,200) at median rhGAA duration ~83 weeks (range, 36-122 weeks). One IOPD patient (7.1%) developed titers in the SIT range and one patient (7.1%) developed titers in the HSAT range. Twelve of the 14 patients (85.7%) that received TLD-MTX remained LT, versus 5/37 HSAT (peak 51,200-409,600), 7/37 SIT (12,800-51,000), and 23/37 LT (200-12,800) among comparators. Results of TLD-MTX coinitiated with rhGAA are encou...Continue Reading

References

Jun 2, 2006·The Journal of Pediatrics·Priya S KishnaniUNKNOWN Infantile-Onset Pompe Disease Natural History Study Group
Jan 9, 2009·The New England Journal of Medicine·Nancy J MendelsohnPriya S Kishnani
Mar 17, 2009·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Marc NicolinoPriya S Kishnani
Sep 25, 2009·Molecular Genetics and Metabolism·Priya S KishnaniY-T Chen
Jun 4, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Suhrad G BanugariaPriya S Kishnani
Sep 6, 2011·Molecular Genetics and Metabolism·Mary-Alice AbbottPriya S Kishnani
Jan 13, 2012·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Yoav H MessingerPriya S Kishnani
Jan 19, 2012·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Deeksha S BaliPriya S Kishnani
Jan 19, 2012·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Emanuela LacanáAmy S Rosenberg
Jun 6, 2012·Molecular Genetics and Metabolism·Lisa D Hobson-WebbPriya S Kishnani
Oct 13, 2012·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Suhrad G BanugariaPriya S Kishnani
Oct 26, 2012·Human Vaccines & Immunotherapeutics·Leslie P CousensAnne S De Groot
Apr 27, 2013·Journal of Child Neurology·Federica DeodatoCarlo Dionisi-Vici
Sep 12, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marguerite S JolyAlexandra M Joseph
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Kathryn L BerrierPriya S Kishnani
Jun 14, 2015·International Immunology·Claudia Mauri, Madhvi Menon
Oct 12, 2014·Molecular Genetics and Metabolism Reports·Baodong SunPriya S Kishnani

❮ Previous
Next ❯

Citations

Oct 20, 2020·International Journal of Neonatal Screening·Barbara K BurtonKhaja Basheeruddin
Nov 19, 2020·International Journal of Neonatal Screening·Can FiciciogluRui Xiao
Feb 10, 2021·International Journal of Neonatal Screening·Barbara K BurtonKhaja Basheeruddin

❮ Previous
Next ❯

Methods Mentioned

BETA
enzyme replacement therapy
enzyme-linked immunosorbent assays

Clinical Trials Mentioned

NCT01665326

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.