Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID).
Adenosine deaminase deficiency (ADA) is a rare, inherited disorder of purine metabolism characterized by immunodeficiency, failure to thrive and metabolic abnormalities. A lack of the enzyme ADA allows accumulation of toxic metabolites causing defects of both cell mediated and humoral immunity leading to ADA severe combined immune deficiency (SCID), a condition that can be fatal in early infancy if left untreated. Hematopoietic stem cell transplant is curative but is dependent on a good donor match. Other therapeutic options include enzyme replacement therapy (ERT) with pegademase bovine (PEG-ADA) and more recently gene therapy. PEG-ADA has been used in over 150 patients worldwide and has allowed stabilization of patients awaiting more definitive treatment with hematopoietic stem cell transplant. It affords both metabolic detoxification and protective immune function with patients remaining clinically well, but immune reconstitution is often suboptimal and may not be long lived. We discuss the pharmacokinetics, immune reconstitution, effects on systemic disease and side effects of treatment with PEG-ADA. We also review the long-term outcome of patients receiving ERT and discuss the role of PEG-ADA in the management of infants and children with ADA-SCID, alongside other therapeutic options.
Booth
Claire
C
Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UK.
Gaspar
H Bobby
HB
J Exp Med. 2000 Jul 17;192(2):159-70
10899903
Pediatrics. 2005 Dec;116(6):e876-9
16263974
Lancet. 1975 Oct 18;2(7938):743-6
52774
Eur J Pediatr. 1992 Nov;151(11):811-4
1468454
Pediatr Res. 1993 Jan;33(1 Suppl):S42-7; discussion S47-8
8433874
Prenat Diagn. 1987 Oct;7(8):561-5
3120171
Br J Haematol. 1984 Jan;56(1):107-19
6231047
Clin Immunol. 2005 Nov;117(2):133-43
16112907
J Pediatr. 1988 Aug;113(2):312-7
3260944
Clin Exp Immunol. 1981 Dec;46(3):649-52
7337981
J Clin Invest. 1981 Aug;68(2):413-21
7263861
Pediatr Res. 1993 Jan;33(1 Suppl):S35-41
8433873
J Clin Invest. 2008 Sep;118(9):3132-42
18688285
N Engl J Med. 2009 Jan 29;360(5):447-58
19179314
Clin Diagn Lab Immunol. 2005 Jul;12(7):861-6
16002636
Nat Med. 2006 Apr;12(4):401-9
16582916
Clin Pediatr (Phila). 2000 Mar;39(3):183-6
10752014
J Biol Chem. 1977 Jun 10;252(11):3582-6
16907
Clin Immunol Immunopathol. 1995 Sep;76(3 Pt 2):S228-32
7554473
Clin Immunol Immunopathol. 1979 Nov;14(3):307-26
498598
J Pediatr. 2007 Jul;151(1):93-5
17586199
N Engl J Med. 1980 Aug 14;303(7):377-80
6156414
J Pediatr. 2001 Jul;139(1):44-50
11445793
J Clin Invest. 1999 Mar;103(6):833-41
10079104
Clin Immunol Immunopathol. 1978 Mar;9(3):287-92
627115
J Med Genet. 1987 Feb;24(2):93-6
3560174
Blood. 1992 Sep 1;80(5):1163-71
1387561
Best Pract Res Clin Haematol. 2004 Sep;17(3):505-16
15498720
J Clin Invest. 1992 May;89(5):1643-51
1569204
Eur J Haematol. 2007 Oct;79(4):338-48
17680812
N Engl J Med. 1996 May 23;334(21):1367-71
8614422
Eur J Immunol. 2005 Nov;35(11):3376-86
16276484
Mol Ther. 2006 Oct;14(4):505-13
16905365
Am J Pathol. 1985 Jul;120(1):157-69
4014441
Pediatr Res. 1990 Aug;28(2):127-30
2395602
J Clin Invest. 2000 Nov;106(9):1149-57
11067867
J Clin Invest. 1993 Aug;92(2):596-602
8349799
J Biol Chem. 2000 Oct 13;275(41):32114-21
10908569
Clin Immunol. 2007 May;123(2):139-47
17300989
Science. 1995 Oct 20;270(5235):475-80
7570001
Lancet. 1972 Nov 18;2(7786):1067-9
4117384
N Engl J Med. 1987 Mar 5;316(10):589-96
3807953
N Engl J Med. 1976 Dec 9;295(24):1337-43
980079