TY - JOUR
T1 - Ethical challenges for a new generation of early-phase pediatric gene therapy trials
AU - Iyer, Alexander A.
AU - Saade, Dimah
AU - Bharucha-Goebel, Diana
AU - Foley, A. Reghan
AU - Averion, Gilberto ‘Mike’
AU - Paredes, Eduardo
AU - Gray, Steven
AU - Bönnemann, Carsten G.
AU - Grady, Christine
AU - Hendriks, Saskia
AU - Rid, Annette
N1 - Funding Information:
The authors thank the patients and families who have supported and participated in the GAN trial. They also thank Benjamin Berkman, Sara Chandros Hull, and David Wendler for feedback on earlier drafts of this paper, and members of the NIH Clinical Center Bioethics Consultation Service for their insights on the GAN trial. This work was supported by the US National Institutes of Health Intramural Research Program.
Funding Information:
Preclinical vector development and later clinical lot production began over 10 years ago, instigated and funded in part by Hannah’s Hope Fund (HHF), a “public charity…to support the development of treatments and a cure for GAN [21].” The GT attempts to deliver an intact and codon-optimized complementary DNA (cDNA) copy of the GAN transcript to the nervous system using an adeno-associated virus 9 (AAV9) vector, administered into the cerebrospinal fluid via lumbar puncture [22]. The GAN trial is novel for administering AAV-mediated GT using an intrathecal delivery route. Thus far, 14 participants (ages 6–14 years at enrollment) from around the world have been enrolled at one of four dose levels.
Publisher Copyright:
© 2021, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2021/11
Y1 - 2021/11
N2 - After decades of setbacks, gene therapy (GT) is experiencing major breakthroughs. Five GTs have received US regulatory approval since 2017, and over 900 others are currently in development. Many of these GTs target rare pediatric diseases that are severely life-limiting, given a lack of effective treatments. As these GTs enter early-phase clinical trials, specific ethical challenges remain unresolved in three domains: evaluating risks and potential benefits, selecting participants fairly, and engaging with patient communities. Drawing on our experience as clinical investigators, basic scientists, and bioethicists involved in a first-in-human GT trial for an ultrarare pediatric disease, we analyze these ethical challenges and offer points to consider for future GT trials.
AB - After decades of setbacks, gene therapy (GT) is experiencing major breakthroughs. Five GTs have received US regulatory approval since 2017, and over 900 others are currently in development. Many of these GTs target rare pediatric diseases that are severely life-limiting, given a lack of effective treatments. As these GTs enter early-phase clinical trials, specific ethical challenges remain unresolved in three domains: evaluating risks and potential benefits, selecting participants fairly, and engaging with patient communities. Drawing on our experience as clinical investigators, basic scientists, and bioethicists involved in a first-in-human GT trial for an ultrarare pediatric disease, we analyze these ethical challenges and offer points to consider for future GT trials.
UR - http://www.scopus.com/inward/record.url?scp=85110024677&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85110024677&partnerID=8YFLogxK
U2 - 10.1038/s41436-021-01245-3
DO - 10.1038/s41436-021-01245-3
M3 - Review article
C2 - 34234300
AN - SCOPUS:85110024677
SN - 1098-3600
VL - 23
SP - 2057
EP - 2066
JO - Genetics in Medicine
JF - Genetics in Medicine
IS - 11
ER -