Government Panel Considers Future of Gene Therapy Research

By Dave Cureton, cancerpage.com

Parental instinct collided with scientific method today (3/9/00) at a meeting of the federal government panel that monitors gene therapy research, some of which is exploring new treatments for various cancers.

Dr. Roger Karlin and Helene Karlin, Ph.D. of New Fairfield, CT, both told the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health in Bethesda, MD that the panel seemed too focused on data and methodology in evaluating experimental treatments of a rare degenerative neurological disease.  Canavan’s disease usually kills its victims before they reach age ten.  The Karlins’ daughter, Lindsay, is five years old and has been taking part in trials at Thomas Jefferson University in Philadelphia.  The Karlins say she has shown dramatic, long-term improvement after each of four experimental gene replacement treatments she’s received. 

RAC members had just finished closely questioning the researchers who’ve been working with Lindsay and other children and who now want to begin using a newly developed type of treatment.  The panel, which has no direct regulatory authority, recommended the researchers present more the safety of the treatment and be more specific about how to determine its effectiveness.

One committee member summed up the need for caution, precision and thoroughness in trials in such a young field as gene therapy, especially involving young children with a terminal disease.  C. Estuardo Aguilar-Cordova, director of Gene Therapy Laboratories at Texas Children’s Hospital, Baylor College of Medicine in Houston, TX, said his family had a saying:  “Please go slow because we’re in a hurry.”    

To the Karlins, the first concern seemed overblown for a disease known to kill young children so quickly and so inevitably.  As for treatment goals, they believe they’ve got living proof of the only one that matters – a child who, once experimental treatments have worn off, is “out of it” and unable to even lift her head, but who can do both relatively soon after treatment and for up to a year afterward.  Most important of all to her parents, Lindsay is still alive.  When it comes to scientific results, said Helene Karlin, “that seems pretty objective to me!”

Lindsay’s mother said, “Parents can be the most acute observers of children,” and ought to be the final arbiters of what’s best for them.  “Our children have an ethical right to this treatment as long as we think it’s safe for them,” she said. 

Speaking of Lindsay and all other children with Canavan’s disease, she told the RAC,  “Every day we wait (for treatment) their brain cells deteriorate.”  Referring to one of the panel’s concerns, she called the risk-benefit ratio of the experimental treatment “incredible.”

The Karlins have more than a passing experience with the rigorous requirements of medical research.  She is a psychologist with a Ph.D. and her husband, Roger, is a physician, a general internist in private practice.  The have three other daughters who’ve never shown signs of Canavan’s, two born before Lindsay, the other adopted.

Later, Helene Karlin called concerns among RAC members about the safety of the trials “ridiculous.”  “My daughter would be dead if we didn’t do the gene therapy,” said Karlin, or if she were still alive, “her brain would be mush.”  She told reporters the RAC “seemed defensive,” and suggested it was because of new controversy over gene therapy following the death last September of Jesse Gelsinger, 18, the first person known to have died directly as a result of experimental gene replacement treatment.

The Food and Drug Administration has placed on indefinite hold the gene therapy studies at the University of Pennsylvania in which Gelsinger was a volunteer.  His father claims he and Gelsinger were misled by researchers about risks, and the FDA said in January that the researchers had violated patient safety regulations.

Dr. Roger Karlin said he does not expect today’s recommendations by the RAC to delay Lindsay’s further treatment.  Meanwhile, the Karlins will continue to try to raise awareness of Canavan’s disease – and raise money for research -- through the foundation they established in 1995, the Canavan Research Foundation ( www.canavan.org ).

SOURCE:

• Cancerpage.com"s coverage of the meeting by the Recombinant DNA Advisory Committee (RAC) of the National Institutes of Health in Bethesda, MD, March 9, 2000.