Non credo. Però che il follow-up debba essere lungo è stabilito dall'FDA. Ho trovato un documento (il primo che ho trovato, del 2002; possibile che esista qualcosa di più recente e aggiornato a vettori che NON si integrano in permanenza, come il rinovirus utilizzato da Sangamo (*)), in cui si sostiene:HLAB5701 ha scritto:Scusa, ma questo cosa implica? che per 15 anni la tecnica non sarebbe disponibile se non al massimo in via caritatevole per i casi disperati?Dora ha scritto: As in all gene therapy studies, he noted, safety follow-up will continue for 15 years.
Current long-term follow-up published guidance
In current guidance documents, FDA’s long-term testing and subjectmonitoring recommendations focus on those subjects treated with retroviral vectors. FDA currently has published no specific recommendations for longterm follow-up of subjects treated with any other classes of gene transfer vectors.
One rationale for recommending long -term follow-up in subjects participating in gene transfer clinical trials using retroviral vectors is based on the fact that these vectors are known to integrate into the genome. The consequences of life-long exposure to the gene product or to the introduced genetic sequences can only be assessed through the long-term follow-up of these patients.
Another reason for long -term follow-up efforts in studies using retroviral vectors is that use of retroviral vectors carries the potential for exposure of patients to replication competent retroviruses (RCR). Retroviral infection, including HIV infection, in many species can result in latent infection with disease appearing years later. In 1993, a report of lymphoma in 3 out of 10 immunosuppressed non-human primates that received retrovirally transduced bone marrow cells with high titer RCR (Donahue, R. E. et al. 1992. Helper virus induced T cell lymphoma in nonhuman primates after retroviral mediated gene transfer. J. Exp. Med. 76:1125-1135) led to recommendations for patient testing for evidence of RCR infection in a 1993 guidance. (...)
Impact of vector characteristics on the approaches to long term follow-up
Current medical and regulatory systems are not well designed to track individual gene therapy study subjects over long periods to identify very late treatment related toxicities (i.e., years later) and to examine causal association with the gene therapy.
Prior to consulting an advisory committee and considering new policy in this area, FDA did substantial background work investigating the types of longterm concerns, the classes of gene therapy products to which they apply, and the feasibility of various approaches to collecting such data.
In these efforts, we gave careful consideration and deliberation not only to the safety issues that need to be addressed but also to the practical difficulties in reliably collecting such data (see section 3.1.2.1).
To detect latent or long-term effects, clinical follow-up for extended periods of time is important. FDA convened the BRMAC on November 16-17, 2000, April 5-6, 2001, and October 24, 2001, to discuss issues pertaining to the long-term follow-up of gene transfer study participants. Deliberations of the committee largely focused on three areas: what types of vectors raised concerns warranting long-term follow-up (briefly summarized in this section), what types of clinical information should be obtained in long-term follow-up (next section), and how such information should be obtained (section 3).
In addition to reviewing the adequacy of current recommendations for studies that use retroviral vectors, BRMAC was asked to consider the appropriate long-term follow-up in conjunction with the growing use of other non-retroviral, RNA- and DNA-based delivery mechanisms (vectors) for which there is no FDA guidance. Briefing materials for BRMAC members included information on vector design, product characterization, preclinical models, known and hypothetical risks associated with vector class and vector properties, procedures for reporting adverse events, the value of centralized database, limitations or barriers to effective data collection and reporting, and types and time courses of late adverse events associated with other types of therapies and infections.
The BRMAC deliberated on the risks associated with RNA- and DNA-based vectors and the various factors that contributed to those risks. They noted that all gene therapy vector systems carry sufficient concerns about long-term side effects to warrant some level of long-term follow-up, but certain categories of gene transfer vectors warranted more attention. BRMAC pointed out vector classes of particular concern included: 1) vectors with the potential to integrate; 2) vectors with the potential to replicate; 3) vectors with altered tropisms; and, 4) vectors with long latency. Some additional vector characteristics were thought to have significant impact on the degree of long - term risk.
For example, integrating vectors have the potential to initiate neoplastic processes depending upon the site of integration or presence of strong promoter/enhancer elements present in the gene transfer vector. Host characteristics such as the immune status of recipient, the route of administration (intra-venous, intra-arterial, subcutaneous, etc.), and the type of cell targeted for transformation (ex-vivo transformation of stem cell, cells capable of division and lasting life cycle vs. irradiated cells, etc) were also discussed and felt to be influential factors.
Recognizing the large number of factors that could influence the nature and degree of long -term risks in any given study, the BRMAC was reluctant to endorse a specific global approach to long-term follow-up based on vector characteristics. Instead, BRMAC recommended that FDA scientists apply scientific principles and judgment to determining appropriate follow-up. (Gene Therapy Patient Tracking System, pp. 9-12)
(*) Ecco, lo sapevo che doveva esserci qualcosa di più recente. Solo che è lunghissimo e non ho tempo di leggerlo: Guidance for Industry Gene Therapy Clinical Trials – Observing Subjects for Delayed Adverse Events.