T-Lymphocyte Gene Transfer for a Patient with ADA-SCID Onodera, M., T. Ariga, N. Kawamura, I. Koboyashi, M. Ohtsu, M. Yamada, A. Tame, H. Furuta, M. Okano, S. Matsumoto, H. Kotani, G.J. McGarrity, R. M. Blaese, and Y. Sakiyama. 1998.
What is ADA-SCID? • ADA is an enzyme • Deficiency impairs immunity responses • Resulting in SCID (Severe Combined Immunodeficiency) • Lack of enzyme of ADA coded for by a gene on chromosome 20 • Causes B and T lymphocytes to function improperly
Symptoms of ADA-SCID • Productive cough and Nasal Discharge • Lymphopenia • Very little mature T and B lymphocytes • Low Ig serum levels • Undetectable isohemagglutinins • No T-cell response to phytohemagglutinins, Concanavalin A, and pokeweed mitogen.
Mutations responsible for ADA deficiency • G632 to A transition (Arginine replaced by Histidine) • RsaI digestion same as father Paternal missense mutation(1c)
Clinical Course After Gene Therapy • 10 infusions and patient had an increase in lymphocyte numbers. Eventually returned to basal levels • PBL count remained in a normal range • Increase in CD8+ count • ADA enzyme activity increased • Immune functions improved • Ig levels increased
Conclusion • ADA-SCID patients had positive outcomes with the genetic therapy • Genetic therapy has established a new form of treatment for people with inherited diseases and acquired diseases