Gene therapy is the isolation of a gene, which is then packaged into a vector for introduction into the body in hopes that it can correct some aspect of genetic disease. Often this “vector” is a type of virus which had been specifically engineered to be safer than its original version. This usually involves removing the exons responsible for its transmission through all cell types, effectively “disabling” it. The virus will infect target cells and force them to produce the protein of interest, effectively replacing (or overexpressing) the protein in the body–which can be perpetuated.
Gene therapy human trials have been suffering from bad press, as there have been a few high-profile deaths during a clinical trial (very few though, in respect to how many people have received the therapy). These deaths are huge setbacks in the public perception of gene therapy as well as the ability to secure funding for future trials. However, the most recent death during a gene therapy trial, that of Jolee Mohr, was just reported to be unrelated to the gene therapy itself. Mohr was involved in a clinical trial testing gene therapy for rheumatoid arthritis in her knee, and died 3 weeks after receiving the injected virus (an adeno-associated virus) and after her death the entire study was halted.
“At a September meeting of the federal Recombinant DNA Advisory Committee (RAC), experts noted that Mohr apparently died mainly from a fungal infection called histoplasmosis that her immune system was unable to fight off.”
Initially, it was hypothesized that the therapy may have contributed to her susceptibility to the infection. She was taking Humira for her arthritis which blocks tumor necrosis factor alpha (TNFa). This is the same protein expressed by the gene therapy, and if the virus had spread beyond her knee, the combination of both might have compromised her immune system. But it is now known for sure that that did not happen, according to the gene therapy company Targeted Genetics.
The level of TNF-α blocker detected in Mohr’s blood with a binding assay was “well within the normal range expected” from the dose of Humira she was taking, says President and CEO H. Stewart Parker. The new tests also ruled out the idea that the gene-therapy vector, adeno-associated virus, replicated in Mohr’s body. Although DNA from the vector turned up in other tissues, the amounts were extremely low.
This finding resulted in the FDA lifting the halt on the clinical trial, which can now resume (and those interested in gene therapy can breathe a sigh of relief.)