title: Safety profile of plasmid/liposomes and virus vectors in clinical gene therapy.
abstract: Despite of more than 500 gene therapy trials worldwide very little systematic safety information is available from gene therapy. Safety information was collected from 146 consecutive patients who participated in three randomized, controlled phase II gene therapy trials in cardiovascular diseases and malignant glioma using adenoviruses, plasmid/liposomes and retrovirus packaging cells. Total follow-up time of the patients was 78794 days which equals 1.5 years per patient. The main outcome measures were serious adverse events, other adverse events and changes in general laboratory parameters. Except fever and increases in CRP values plasmid/liposomes were safe and well tolerated. The incidence of serious adverse events in adenovirus-treated patients was 0.9 and 4.0/10000 patient days in cardiovascular and malignant glioma trials as compared to 0.5 and 2.1 in randomized control patients, respectively. Transient fever, leukopenia and increases in CRP and liver enzymes were detected in virus-treated patients. No deaths from side effects or no new cancers were associated with gene therapy. It is concluded that gene therapy, like any other therapy, is associated with side effects which depend on the administered vector, dose, and route of delivery and properties of the transgene. However, given the limitations of this study and length of the follow-up, the safety profile of gene therapy seems to be acceptable for the treatment of severe human diseases.
authors.affiliation: A.I. Virtanen Institute, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wirth
authors.forename: Marja
authors.initials: M
authors.lastname: Hedman
authors.forename: Kimmo
authors.initials: K
authors.lastname: Mäkinen
authors.forename: Hannu
authors.initials: H
authors.lastname: Manninen
authors.forename: Arto
authors.initials: A
authors.lastname: Immonen
authors.forename: Matti
authors.initials: M
authors.lastname: Vapalahti
authors.forename: Seppo
authors.initials: S
authors.lastname: Ylä-Herttuala
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000628:therapy; D017322:Clinical Trials, Phase II as Topic; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D005500:Follow-Up Studies; D015316:Genetic Therapy / Q000009:adverse effects* / Q000401:mortality; D005822:Genetic Vectors / Q000009:adverse effects*; D005910:Glioma / Q000150:complications / Q000628:therapy; D006801:Humans; D008081:Liposomes / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000009:adverse effects* / Q000235:genetics; D016032:Randomized Controlled Trials as Topic
chemical_list: D004337:Drug Carriers; D008081:Liposomes