- Email: [email protected]
Remodeling the NGVL Program to Meet Contemporary Needs
editorials
© The American Society of Gene Therapy
doi:10.1038/sj.mt.6300226
NIH Decides Against Continuing NGVLs in Their Current Form
D
uring the American Society of Gene Therapy (ASGT) Annual Meeting in 2006, there were many conversations concerning the potential discontinuation of the National Gene Vector Laboratories (NGVL) program by the National Institutes of Health (NIH). In light of concerns about what the NIH might be planning, Dr. Ted Friedmann, President of the ASGT, assembled an ad hoc committee to review the funding of gene therapy trials and to recommend a position on NGVLs for the society to communicate to the NIH. In editorials published in Molecular Therapy in November 2006 (“NIH Funding of Gene Therapy Trials”) and January 2007 (“ASGT Advises NIH in Funding of Gene Therapy Trials”), we expressed the strong view that NIH should revamp the way in which gene therapy trials are funded and that the NGVL program had been a valuable mechanism by which clinical-grade vectors were produced and certified. The ad hoc committee strongly urged that the NGVL program be continued, albeit with modifications in the review process that would be intended to make the entire process less cumbersome and more efficient. In a letter to Dr. Friedman dated 22 February 2007, Dr. Elias Zerhouni, Director of the NIH, thanked the ASGT for its input and informed him that the NIH would no longer fund vector production via NGVLs. However, there will be continued resources for repositories where master cell banks could be stored. Zerhouni explained that both the National Cancer Institute and the National Heart, Lung, and Blood
Institute—which were major funding institutes for the NGVL—had decided to fund their own vector production centers. This is a disappointing course of action contrary to what the ASGT and end-users in the field recommended. It is ironic that Dr. Zerhouni should make this decision to further fragment vector funding, because his mantra has clearly been a call for trans-NIH programs that facilitate collaborative approaches to biology and therapy in a non-disease-specific fashion. I would argue that the NGVL was a successful example of this approach and, although not perfect, served an extremely useful purpose for the field. Apparently, considerations of the ASGT recommendations on the fundamental process by which gene therapy trials are funded by the NIH are still under consideration. In his letter to Dr. Friedman, Dr. Zerhouni said that he has “asked Amy Patterson of the Office of Biotechnology Activities to confer with relevant NIH Institutes and Centers regarding the problems that you (ASGT) identified and your recommendations.” One can only hope that the NIH is more amenable to follow-through on the thoughtful recommendations by the ASGT on new approaches for reviewing and funding gene therapy research. In the current climate, the field (as is NIH-supported research in general) is significantly underfunded, and, in addition, the process is nonharmonized and excessively burdensome.
David A Williams Editor-in-Chief
Remodeling the NGVL Program to Meet Contemporary Needs
N
ational Institutes of Health (NIH) initiatives to support studies of gene therapy peaked in the 1990s as attempts were made to build on experience gained with adenosine deaminase deficiency. The National Center for Research Resources’ (NCRR) National Gene Vector Laboratory (NGVL) program was started in 1995 to encourage the production of clinical-grade vectors under Good Molecular Therapy vol. 15 no. 7 july 2007
Manufacturing Practice conditions and to create a forum for the exchange of ideas, experiences, and data among experts in the field. The setbacks in the treatment of ornithine transcarbamylase deficiency and X-linked severe combined immunodeficiency temporarily slowed advances, but new highly targeted initiatives were published by categorical NIH institutes in 2006. These included the National 1223
© The American Society of Gene Therapy
editorials
Heart, Lung, and Blood Institute’s “New Approaches to NonViral Systems for Gene Transfer Applications for Heart, Lung, and Blood Diseases” (http://grants.nih.gov/grants/guide/pa-files/PA-06243.html) and the development of primate models, such as “RNAi and Therapeutic Targeting to Model Gene Therapy in Monkeys: The 6th Annual Gene Therapy Symposium for Heart, Lung, and Blood Diseases Focus Topic” (http://www.gts.ucdavis.edu/2007.htm). The National Cancer Institute has also reported successes, as in a 2006 article in Science, “Cancer Regression in Patients after Transfer of Genetically Engineered Lymphocytes.” Advances in these defined areas have been accompanied by a reduction in the overall number of NIH institutes supporting gene therapy research, and this change in balance required that NCRR re-evaluate the role of the NGVL. It soon became clear that the number of NIH Institutes and Centers availing themselves of NGVL resources had fallen below a level at which NCRR could reasonably be said to be meeting its mission to “accelerate and enhance research along the entire continuum of biomedical science, to stimulate basic research to develop versatile new technologies and methods that help researchers to study virtually every human disease.” New vector-production resources have been brought on line since 1995, and patient safety, including the potential for delayed adverse events, still has the highest priority. The U.S. Food and Drug Administration (FDA) recommends that human subjects exposed to the risk of delayed toxic effects be observed for as long
1224
as 15 years (for U.S. FDA guidance, see “Gene Therapy Clinical Trials—Observing Subjects for Delayed Adverse Events,” http:// www.fda.gov/cber/gdlns/gtclin.htm), so resources to archive biologic material are essential in the investigation of delayed toxic effects related to exposure to a gene therapy product. Furthermore, acute toxicity associated with gene therapy may stem from the vector, and gene therapy products often use vectors that are the same as or similar to vectors for which the NGVL currently has data from toxicology and biodistribution studies. Making the data from these and other studies available in a searchable toxicology and biodistribution database (as is proposed for the National Gene Vector Biorepository and Coordinating Center (P40), RFARR-07-002; see http://www.ncrr.nih.gov/ncrrprog/clindir/NGVL. asp) should save researchers both time and resources. If this new NCRR initiative can complement the new opportunities for gene therapy being offered through the categorical institutes, then it will go some way toward addressing the investigators’ needs.
Anthony R Hayward Director, Division for Clinical Research Resources, National Center for Research Resources, National Institutes of Health, Bethesda, Maryland, USA Correspondence: [email protected]
REFERENCES 1.
Morgan RA, Dudley, ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006; 314: 126–9.
www.moleculartherapy.org vol. 15 no. 7 july 2007
© The American Society of Gene Therapy
doi:10.1038/sj.mt.6300226
NIH Decides Against Continuing NGVLs in Their Current Form
D
uring the American Society of Gene Therapy (ASGT) Annual Meeting in 2006, there were many conversations concerning the potential discontinuation of the National Gene Vector Laboratories (NGVL) program by the National Institutes of Health (NIH). In light of concerns about what the NIH might be planning, Dr. Ted Friedmann, President of the ASGT, assembled an ad hoc committee to review the funding of gene therapy trials and to recommend a position on NGVLs for the society to communicate to the NIH. In editorials published in Molecular Therapy in November 2006 (“NIH Funding of Gene Therapy Trials”) and January 2007 (“ASGT Advises NIH in Funding of Gene Therapy Trials”), we expressed the strong view that NIH should revamp the way in which gene therapy trials are funded and that the NGVL program had been a valuable mechanism by which clinical-grade vectors were produced and certified. The ad hoc committee strongly urged that the NGVL program be continued, albeit with modifications in the review process that would be intended to make the entire process less cumbersome and more efficient. In a letter to Dr. Friedman dated 22 February 2007, Dr. Elias Zerhouni, Director of the NIH, thanked the ASGT for its input and informed him that the NIH would no longer fund vector production via NGVLs. However, there will be continued resources for repositories where master cell banks could be stored. Zerhouni explained that both the National Cancer Institute and the National Heart, Lung, and Blood
Institute—which were major funding institutes for the NGVL—had decided to fund their own vector production centers. This is a disappointing course of action contrary to what the ASGT and end-users in the field recommended. It is ironic that Dr. Zerhouni should make this decision to further fragment vector funding, because his mantra has clearly been a call for trans-NIH programs that facilitate collaborative approaches to biology and therapy in a non-disease-specific fashion. I would argue that the NGVL was a successful example of this approach and, although not perfect, served an extremely useful purpose for the field. Apparently, considerations of the ASGT recommendations on the fundamental process by which gene therapy trials are funded by the NIH are still under consideration. In his letter to Dr. Friedman, Dr. Zerhouni said that he has “asked Amy Patterson of the Office of Biotechnology Activities to confer with relevant NIH Institutes and Centers regarding the problems that you (ASGT) identified and your recommendations.” One can only hope that the NIH is more amenable to follow-through on the thoughtful recommendations by the ASGT on new approaches for reviewing and funding gene therapy research. In the current climate, the field (as is NIH-supported research in general) is significantly underfunded, and, in addition, the process is nonharmonized and excessively burdensome.
David A Williams Editor-in-Chief
Remodeling the NGVL Program to Meet Contemporary Needs
N
ational Institutes of Health (NIH) initiatives to support studies of gene therapy peaked in the 1990s as attempts were made to build on experience gained with adenosine deaminase deficiency. The National Center for Research Resources’ (NCRR) National Gene Vector Laboratory (NGVL) program was started in 1995 to encourage the production of clinical-grade vectors under Good Molecular Therapy vol. 15 no. 7 july 2007
Manufacturing Practice conditions and to create a forum for the exchange of ideas, experiences, and data among experts in the field. The setbacks in the treatment of ornithine transcarbamylase deficiency and X-linked severe combined immunodeficiency temporarily slowed advances, but new highly targeted initiatives were published by categorical NIH institutes in 2006. These included the National 1223
© The American Society of Gene Therapy
editorials
Heart, Lung, and Blood Institute’s “New Approaches to NonViral Systems for Gene Transfer Applications for Heart, Lung, and Blood Diseases” (http://grants.nih.gov/grants/guide/pa-files/PA-06243.html) and the development of primate models, such as “RNAi and Therapeutic Targeting to Model Gene Therapy in Monkeys: The 6th Annual Gene Therapy Symposium for Heart, Lung, and Blood Diseases Focus Topic” (http://www.gts.ucdavis.edu/2007.htm). The National Cancer Institute has also reported successes, as in a 2006 article in Science, “Cancer Regression in Patients after Transfer of Genetically Engineered Lymphocytes.” Advances in these defined areas have been accompanied by a reduction in the overall number of NIH institutes supporting gene therapy research, and this change in balance required that NCRR re-evaluate the role of the NGVL. It soon became clear that the number of NIH Institutes and Centers availing themselves of NGVL resources had fallen below a level at which NCRR could reasonably be said to be meeting its mission to “accelerate and enhance research along the entire continuum of biomedical science, to stimulate basic research to develop versatile new technologies and methods that help researchers to study virtually every human disease.” New vector-production resources have been brought on line since 1995, and patient safety, including the potential for delayed adverse events, still has the highest priority. The U.S. Food and Drug Administration (FDA) recommends that human subjects exposed to the risk of delayed toxic effects be observed for as long
1224
as 15 years (for U.S. FDA guidance, see “Gene Therapy Clinical Trials—Observing Subjects for Delayed Adverse Events,” http:// www.fda.gov/cber/gdlns/gtclin.htm), so resources to archive biologic material are essential in the investigation of delayed toxic effects related to exposure to a gene therapy product. Furthermore, acute toxicity associated with gene therapy may stem from the vector, and gene therapy products often use vectors that are the same as or similar to vectors for which the NGVL currently has data from toxicology and biodistribution studies. Making the data from these and other studies available in a searchable toxicology and biodistribution database (as is proposed for the National Gene Vector Biorepository and Coordinating Center (P40), RFARR-07-002; see http://www.ncrr.nih.gov/ncrrprog/clindir/NGVL. asp) should save researchers both time and resources. If this new NCRR initiative can complement the new opportunities for gene therapy being offered through the categorical institutes, then it will go some way toward addressing the investigators’ needs.
Anthony R Hayward Director, Division for Clinical Research Resources, National Center for Research Resources, National Institutes of Health, Bethesda, Maryland, USA Correspondence: [email protected]
REFERENCES 1.
Morgan RA, Dudley, ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006; 314: 126–9.
www.moleculartherapy.org vol. 15 no. 7 july 2007