T-Lymphocyte Gene Transfer for a Patient with ADA-SCID

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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.

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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

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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.

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Mutations responsible for ADA deficiency

• G632 to A transition (Arginine replaced by
  Histidine)
• RsaI digestion same as father
• Paternal missense mutation(1c)

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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

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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