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Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase.

Publication ,  Journal Article
Hershfield, MS; Buckley, RH; Greenberg, ML; Melton, AL; Schiff, R; Hatem, C; Kurtzberg, J; Markert, ML; Kobayashi, RH; Kobayashi, AL
Published in: N Engl J Med
March 5, 1987

We treated two children who had adenosine deaminase deficiency and severe combined immunodeficiency disease by injecting bovine adenosine deaminase modified by conjugation with polyethylene glycol. The modified enzyme was rapidly absorbed after intramuscular injection and had a half-life in plasma of 48 to 72 hours. Weekly doses of approximately 15 U per kilogram of body weight maintained plasma adenosine deaminase activity at two to three times the level of erythrocyte adenosine deaminase activity in normal subjects. The principal biochemical consequences of adenosine deaminase deficiency were almost completely reversed. In erythrocytes, adenosine nucleotides increased and deoxyadenosine nucleotides decreased to less than 0.5 percent of total adenine nucleotides. The activity of S-adenosylhomocysteine hydrolase, which is inactivated by deoxyadenosine, increased to normal in red cells and nucleated marrow cells. Neither toxic effects nor hypersensitivity reactions were observed. In vitro tests of the cellular immune function of each patient showed marked improvement, along with an increase in circulating T lymphocytes. Clinical improvement was indicated by absence of infection and resumption of weight gain. We conclude that from the standpoints of efficacy, convenience, and safety, polyethylene glycol-modified adenosine deaminase is preferable to red-cell transfusion as a treatment for adenosine deaminase deficiency. Patients with other inherited metabolic diseases in which accumulated metabolites equilibrate with plasma could benefit from treatment with the appropriate polyethylene glycol-modified enzyme.

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Published In

N Engl J Med

DOI

ISSN

0028-4793

Publication Date

March 5, 1987

Volume

316

Issue

10

Start / End Page

589 / 596

Location

United States

Related Subject Headings

  • Polyethylene Glycols
  • Nucleoside Deaminases
  • Injections, Intramuscular
  • Immunologic Deficiency Syndromes
  • Hydrolases
  • Humans
  • General & Internal Medicine
  • Female
  • Erythrocytes
  • Child, Preschool
 

Citation

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Hershfield, M. S., Buckley, R. H., Greenberg, M. L., Melton, A. L., Schiff, R., Hatem, C., … Kobayashi, A. L. (1987). Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase. N Engl J Med, 316(10), 589–596. https://doi.org/10.1056/NEJM198703053161005
Hershfield, M. S., R. H. Buckley, M. L. Greenberg, A. L. Melton, R. Schiff, C. Hatem, J. Kurtzberg, M. L. Markert, R. H. Kobayashi, and A. L. Kobayashi. “Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase.N Engl J Med 316, no. 10 (March 5, 1987): 589–96. https://doi.org/10.1056/NEJM198703053161005.
Hershfield MS, Buckley RH, Greenberg ML, Melton AL, Schiff R, Hatem C, et al. Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase. N Engl J Med. 1987 Mar 5;316(10):589–96.
Hershfield, M. S., et al. “Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase.N Engl J Med, vol. 316, no. 10, Mar. 1987, pp. 589–96. Pubmed, doi:10.1056/NEJM198703053161005.
Hershfield MS, Buckley RH, Greenberg ML, Melton AL, Schiff R, Hatem C, Kurtzberg J, Markert ML, Kobayashi RH, Kobayashi AL. Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase. N Engl J Med. 1987 Mar 5;316(10):589–596.
Journal cover image

Published In

N Engl J Med

DOI

ISSN

0028-4793

Publication Date

March 5, 1987

Volume

316

Issue

10

Start / End Page

589 / 596

Location

United States

Related Subject Headings

  • Polyethylene Glycols
  • Nucleoside Deaminases
  • Injections, Intramuscular
  • Immunologic Deficiency Syndromes
  • Hydrolases
  • Humans
  • General & Internal Medicine
  • Female
  • Erythrocytes
  • Child, Preschool