MFG-IRAP University of Pittsburgh.
The University of Pittsburgh is developing an MFG-IRAP gene therapy for the potential treatment of arthritis. Clinical studies have commenced, including one trial in arthritis patients [225365]. A retrovirus (MFG-IRAP) is used in the ex vivo transfer of a cDNA encoding the human interleukin-1 receptor antagonist (IL-1ra). The therapy is being tested in post-menopausal women, and involves the removal of some of their synovium, which is then transfected with the IRAP gene and reimplanted into the joint. The production of IL-1, 6, 8 and PGE2 is monitored [188197]. In the first clinical trial, a 68-year old woman received cultured synovial cells, transfected with the gene, in two knuckles. Two other knuckles received normal cells and acted as a control. The therapy was well-tolerated and successful transfer and expression of the therapeutic gene were detected. Three further post-menopausal women less than 75 years old are undergoing treatment and nine will be recruited all together [233384]. The initial studies were sponsored by Procter & Gamble [156779]. In rabbits, expression of IL-1ra in the lavage fluid of knees was evident for 4 to 6 weeks following ex vivo introduction of the gene into the synovial lining by the retrovirus construct. Levels were sufficient to offer protection in the inflammatory antigen-induced arthritis model [248952].
Baragi
V M
VM
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48105, USA. baragiv@aa.wl.com