Controversial Gene Therapy Trial Was Poorly Designed, Says Doctor

The gene therapy taken by Jolee Mohr was supposed to work by suppressing her body's immune system in a single place. However, Mohr also took arthritis drugs that broadly suppressed her immune system. Kyle Hogarth, the pulmonologist who treated Mohr during her last days and has tried to determine if the therapy played a role in her death, called this "bad science."

I covered his criticisms and Targeted Genetics' response yesterday, then emailed Hogarth and asked him to further explain why Mohr and other people taking immunosuppressants shouldn't have been in the trial. Responded Hogarth,

The purpose of Phase I testing is safety and dose study. It is not meant to be additive therapy to drugs in the same class. In order to prove safety of a gene product whose sole purpose is to provide TNFa blockade, then how can you allow the person to be on systemic TNFa blockade?

If there is a complication of TNFa blockage, then we don't know the true cause (like in this case). Disseminated Histoplasmosis from TNFa blockers is well described. Not shocking that she had histo given that she was on TNFa blockers. The whole problem is trying to figure out what did it.....we have indirect evidence of no spread of the AAV, and
I believe this. But it would not have been necessary to prove this if we had been able to measure accurately the levels of the various drugs in her blood (to distinguish the types of TNFa blockers she had).

When people are in Phase I chemo trials, they are not getting other chemo at the same time. Why not? Because when you get side effects, I need to know what caused it. I need to also know what is the correct
"dose" (or in this case, innoculum) that I can safely give to measure an output without seeing toxicity.

I'm sure [Targeted Genetics] didn't like my comment. But it's accurate.

See Also:

• Gene Therapy Death Still a Mystery
• Ruling Out a Few Causes of Possible Gene Therapy Death
• How to Run a Better Clinical Trial
• The Ethical Challenge of Gene Therapy Trials
• More Problems With Controversial Gene Therapy Trial Design
• Tests Clear Gene Therapy of Jolee Mohr's Death, but Targeted Genetics Doesn't Learn Lesson