[Gene therapy for adenosine deaminase deficiency].
نویسنده
چکیده
Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency is a fatal recessive disorder caused by mutations in the gene encoding ADA. Based on the first clinical trial of two young girls with ADA-deficient SCID by recombinant retrovirus-mediated gene transfer at the National Institute of Health of USA, we prepared to treat a four-year-old boy with ADA-deficient SCID who had been treated with PEG-ADA for 3 years. Approval to perform the clinical trial of gene therapy by using his peripheral blood T lymphocytes as the target and recombinant retroviral vector (LASN) as the vector for ADA gene transfer was obtained from both of the Ministry of Health and Welfare and the Ministry of Education, Science, Sports and Culture on 13 February, 1995. The first clinical trial of gene therapy for the patient was initiated on 1 August 1995. He received 8 x 10(8) LASN-transduced lymphocytes in an injection administered intravenously on 8 August and 2.5 x 10(9) transduced lymphocytes on 4 September without any side reactions. The procedure, safety and efficacy of clinical trial of gene therapy were discussed.
منابع مشابه
Gene therapy of primary T cell immunodeficiencies.
Gene therapy of severe combined immunodeficiencies has been proven to be effective to provide sustained correction of the T cell immunodeficiencies. This has been achieved for 2 forms of SCID, i.e SCID-X1 (γc deficiency) and adenosine deaminase deficiency. Occurrence of gene toxicity generated by integration of first generation retroviral vectors, as observed in the SCID-X1 trials has led to re...
متن کاملP-115: The Role of G22A Adenosine Deaminase 1 Gene Polymorphism and The Activities of ADA Isoenzymes in Fertile and Infertile Men
Background Some studies have revealed enzymatic and non-enzymatic roles of adenosine deaminase (ADA) in male reproductive system such as regulating adenylate cyclase activity by decreasing adenosine concentration, helping to interaction between prostasomes and spermatozoa. MaterialsAndMethods frequency distribution of ADA1 G22A alleles and genotypes in 200 fertile and 200 infertile men. The pol...
متن کاملSuccessful peripheral T-lymphocyte-directed gene transfer for a patient with severe combined immune deficiency caused by adenosine deaminase deficiency.
Ten patients with adenosine deaminase deficiency (ADA-) have been enrolled in gene therapy clinical trials since the first patient was treated in September 1990. We describe a Japanese ADA- severe combined immune deficiency (SCID) patient who has received periodic infusions of genetically modified autologous T lymphocytes transduced with the human ADA cDNA containing retroviral vector LASN. The...
متن کاملNeutropenia in patients with adenosine deaminase deficiency
Background Adenosine deaminase (ADA) deficiency is a disorder where the accumulation of purine metabolites, which are particularly toxic to lymphocytes, can lead to severe, life threatening infections. In addition, ADA deficiency also affects other tissues. Few reports describe the presence of neutropenia in these patients, primarily in older patients after hematopoietic stem cell transplantati...
متن کاملGene therapy enters the pharma market: The short story of a long journey
Approximately 20 years ago, gene therapy was first introduced when Michael Blaese and colleagues applied ex vivo modified autologous T cells to children suffering from adenosine deaminase deficiency (ADA-SCID), a Mendelian genetic error that causes severe combined immunodeficiency syndrome (Blaese et al, 1995). The investigators used retroviral vectors; the most advanced gene delivery system at...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- [Hokkaido igaku zasshi] The Hokkaido journal of medical science
دوره 71 1 شماره
صفحات -
تاریخ انتشار 1995