BioWorld International Correspondent
PARIS - A second child has developed a serious complication while undergoing gene therapy at the Necker children's hospital in Paris.
The Phase I/II trial was testing a therapy for a rare genetic disease, severe combined immune deficiency linked to the X chromosome (SCID-X1), with which some male babies are born. It was halted last summer after a child suffered from an excessive proliferation of a particular population of T lymphocytes in his blood, a condition akin to leukemia. (See BioWorld International, Oct. 9, 2002.)
SCID-X1 is characterized by an inability to generate T lymphocytes, caused by the faulty expression or function of a protein called gamma-c, which deprives it of a viable defense against infection. The gene therapy being tested entails the ex vivo transfer of a normal copy of the gamma-c gene into medullar cells taken from the patient and reintroduced using a viral vector.
Until the cell proliferation problem was discovered in the subjects, the therapy had appeared to be successful in treating SCID-XI, since eight of the 10 babies who received it began generating T lymphocytes.
The disclosure of the second complication has brought into question the concept of using retroviral vectors to transfer genes. The phenomenon, known as insertional mutagenesis, was described by the French French Agency for the Safety and Hygiene of Health Products (AFSSPS) as a "known, but very slight risk" of gene therapy that uses retroviral vectors.
The medical team that conducted the trial is investigating the two cases to discover the precise cell proliferation mechanism and to determine whether these complications are linked to the mechanics of the therapy, to the nature of the original disease or to the very young age of the patients.