doi:10.1006/mthe.2002.0665, available online at http://www.idealibrary.com on IDEAL
MEETING REPORT
Gene Therapy Coming of Age in Latin America Osvaldo Podhajcer,1,2 Fernando Pitossi,1,2 and Estuardo Aguilar-Cordova3,4,* 1Leloir
Institute, 2University of Buenos Aires, Buenos Aires, Argentina Gene Therapy Initiative, Harvard Medical School, Boston, Massachusetts, USA 4Advantagene, Inc., San Diego, California, USA *To whom correspondence and reprints requests should be addressed. Fax: (617) 432-6191. E-mail:
[email protected]. 3Harvard
“Gene Therapy in Latin America: From the Bench to the Clinic,” a meeting sponsored by the Wellcome Trust and the United Nations University through the Biotechnology Program for Latin America and the Caribbean, took place in Buenos Aires, Argentina from May 20 to 22. This symposium, which was hosted by Osvaldo Podhajcer and Fernando Pitossi, had more than 150 basic scientists and physician-scientists from academia, government and industry in Latin America, similar to the first meeting of the Asociación Iberoamericana de Terapia Génica (Iberoamerican Society of Gene Therapy, AITG) held in Guadalajara, México, two years ago. Participants represented Argentina, México, Brazil, Chile, Uruguay, Costa Rica, Colombia, Venezuela, and Guatemala, with guests from the United States and Europe. All came together to discuss the latest developments in this field in the region. A primary objective of this gathering was to bring together Latin American scientists involved in gene therapy to strengthen continental collaborations and to further disseminate the scientific expertise available in Latin America. The symposium was followed by a 10-day practical course for 25 students from all over Latin America. Presentations included several studies on basic research using a wide array of vector platforms and disease models. For example, Bryan Strauss and Eugenia Costanzi (Sao Pablo University, Brazil) presented their work on p53 activation of LTRs driving expression of retroviral vectors carrying multiple tumor suppressor genes. An interesting presentation was provided by San Wong Han (University of Sao Pablo, Brazil), showing that mouse and human keratinocytes were induced to enter apoptosis following the expression of bsr, a gene that confers resistance to blasticidine, indicating a possible selection mechanism. Nance Nardi (Rio Grande do Sul University, Brazil) talked about her latest findings in hematopoietic stem cell characterization and their potential applications. Diana Jerusalinsky (University of Buenos Aires, Argentina) presented her work with herpes simplex virus-derived vectors in studies for the treatment of pain and memory. Rodolfo Goya (University of La Plata, Argentina) talked about gene therapy of prolactinomas using suicide genes and viral vectors. Gabriel
MOLECULAR THERAPY Vol. 6, No. 2, August 2002 Copyright © The American Society of Gene Therapy
Rabinovich (Hospital de Clinicas, Buenos Aires, Argentina) presented his data on galectin-1 in rheumatoid arthritis. Gerardo Glikin and Liliana Finóchiaro (Roffo Institute and University of Buenos Aires, Argentina) described preliminary veterinary clinical work with nonviral transfer of suicide genes for treating canine spontaneous melanoma. Fernando Pitossi presented his recent work on adenoviral gene transfer with tumor necrosis factor (TNF) on models of Parkinson’s disease, and co-organizer, Osvaldo Podhajcer, showed very recent data on gene combination approaches on immunogenetic therapy of adenocarcinomas. One of the most unique applications was described by Yedi Israel and Amalia Sapag (Laboratory of Genetic Pharmacotherapy, University of Chile), who use antisense oligonucleotides and ribozymes for treating a metabolic disorder of alcoholism that is related to the aldehyde dehydrogenase enzyme. Paulina Mabe (University of Chile) presented her studies of the in vivo selective expansion of cells as a first step to treat mucopolisaccharidosis type VI. Whereas the first two days were centered on basic and preclinical research, the last day of the meeting focused on clinical trials and regulatory issues. Estuardo AguilarCordova (Harvard Gene Therapy Initiative, USA and President of AITG) gave the plenary lecture on the process of clinical trial development in gene therapy and on his own experience in the field with prostate cancer as a model. Augusto Rojas-Martínez presented an update on the first clinical trial in Latin America, at the University of Nuevo Leon in Monterrey, that is being carried out in prostate cancer patients and uses suicide genes. Carlos Melo (BioSidus, Inc., Argentina) shared his experience on large scale preparation of plasmid vectors for clinical trials. Several invited speakers from the United States and Europe (Yuti Chernajovsky, David Gould, and Daniel Anthony from the University of London and Southampton, United Kingdom; Guillermo Mazzolini from the University of Navarra, Spain; Juan Lama, from the University of California, San Diego, La Jolla CA; and Mirta Grifman from Immusol, San Diego, CA) gave talks on other issues such as lentiviral and AAV vectors, transcriptional regulation, immune responses, and ethical issues in clinical trials. Finally, Patricia Saidon, who is in charge of the approval of gene therapy clinical trials for the Ministry of Health in Argentina (equivalent to the
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MEETING REPORT
doi:10.1006/mthe.2002.0665, available online at http://www.idealibrary.com on IDEAL
Molecular Therapy reaches the Iguazu falls and keeps Drs. Estuardo AguilarCordova and Laura Aguilar from getting wet.
FDA), gave an update on the status of the regulatory aspects of Latin American countries with regard to clinical trials in general. It was most interesting to observe the continuing increase in the numbers of earlier stage studies. In the past, most of the clinical studies in Latin America were Phase IV; now there is a trend toward earlier participation, although there are still very few Phase I and II studies. The closing presenter was Laura Aguilar (Harvard gene therapy initiative), who shared her experience with developing clinical protocols and with the prevailing regulatory issues in the United States. This presentation generated great discussion on the need to include Latin
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America in the movement for international harmonization of clinical trial management. Such harmonization may further promote the participation of Latin American investigators and patients in early stage clinical trials. A lively discussion centered around the need for strict regulations for the authorization of clinical trials, the urge for patients to have the hope of new treatments for uncurable diseases, and the role of pharmaceutical companies in developing and promoting clinical trials. As a general conclusion, it was agreed that future clinical trials using gene therapy should be ruled by a common, comprehensive regulation that guarantees standards equivalent to good manufacturing practice (GMP) and good clinical practice (GCP) during the trials. Whether the effort in gene therapy research in Latin America is or should be focused on diseases with primary impact in the region was also discussed. A commitment to redouble efforts toward communication and collaboration among the groups was agreed on. It was impressive that most groups in the field have consolidated their work and that the first gene therapy clinical trial in Latin America was in cancer and is almost completed. All participants left the meeting with the same feeling: gene therapy in Latin America is no longer just a hope but is a field of increasing growth. It was perceived that a fine blend of Latin American flavors was already melting and contributing to the international aroma of gene therapy.
MOLECULAR THERAPY Vol. 6, No. 2, August 2002 Copyright © The American Society of Gene Therapy
