GENE THERAPY: Study Shows Treatment Caused Teen’s Death

      Gene therapy treatment caused the Sept. 17 death of a teenager during a University of Pennsylvania experiment, the Washington Post reports. But preliminary findings of a two-month internal investigation reveal that an adverse reaction to the therapy involving the administration of a gene-modified cold virus called adenovirus -- not researchers' error -- is to blame for 18 year-old Jesse Gelsinger's fatal respiratory distress. Although many research participants have died from pre-existing medical conditions, Gelsinger's death is the first attributed to gene therapy treatment itself (Nelson/Weiss, 12/2). Lead UPenn research James Wilson said, "The (virus) did indeed initiate a sequence of events that led to the patient's death" (Friend, USA Today, 12/2). UPenn researchers disclosed a summary of their findings yesterday, but declined to provide supporting proof until next week's public presentation to the federal oversight board for gene therapy research (Washington Post 12/2).

Too Much Too Soon?
      Gelsinger's death has prompted additional scrutiny of the already controversial world of gene therapy; a nine year-old research field attempting to cure inherited diseases through gene modification. Moreover, the discovery likely will "shake the confidence of researchers," who until now, believed the use of adenovirus to deliver genes was safe. Since 1990, when the first gene therapy experiments took place, about 4,000 patients have participated in more than 350 gene therapy trials; however, the UPenn trial was one of only a few to infuse adenovirus into the bloodstream or liver the Philadelphia Inquirer reports. Based on data from an internal investigation, UPenn researchers are advising that the adenovirus treatment used in the Gelsinger case be halted until further research proves its safety. The most concerning fact about the case, UPenn's Wilson noted, is that none of the UPenn Institute for Human Gene Therapy's animal studies indicated that adenovirus would result in such an immune reaction. He stated, "It's scary having no reliable animal models." The Inquirer also notes that the finding will most likely "rekindle a debate" about using gene therapy participants who are not "close to death." The UPenn trial was the first in the nation to use "relatively healthy" patients (Drake, 12/2).

At What Cost?
      Gelsinger's death, which occurred within four days after the adenovirus infusion, also prompted questions about conflicts of interest among gene therapy researchers. The Washington Post raised questions as to whether Wilson's financial ties to the Sharon Hill, PA-based biotech firm Genova pushed him to enter into human trials too quickly. The Post reported that Wilson forged ahead with human trials despite the deaths of research animals in toxicity studies (Nelson/Weiss, 12/2). But Wilson insists that his plans for the trial preceded his involvement with Genova, which provides the UPenn Institute with $4.7 million annually for research -- about 20% of the total lab budget. But the UPenn tragedy has raised questions regarding the reporting accuracy of gene therapy researchers nationwide, many of whom maintain financial stakes in the research outcomes. Both the FDA and NIH oversight boards have proposed increased regulations over gene therapy as a result. Meanwhile, gene therapy researchers have been banned from enrolling new participants in trials using the adenovirus until further investigation is complete. UPenn Institute sent a 337-page investigative report on the death to the ORDA -- Office of Recombinant DNA Activities -- which plans to review the findings at its quarterly meeting next week (Drake, 12/2).