The French biotechnology institute Genethon is perhaps best known for its unusual funding source — annual television appeals — and for its mapping of the human genome in the early 1990s (I. Chumakov et al. Nature 359, 380–387; 1992). Now, after spending years in the scientific doldrums, it plans to become known as the European centre that can speed up the process of getting gene therapy for rare genetic disorders into routine clinical practice.
Scientific director Fulvio Mavilio, a molecular biologist who took office earlier this month, has a mandate to sharpen the research profile of the institute, which employs 180 scientific staff at its base just outside Paris. One of his main strategies is to create international clinical networks for gene therapy around Genethon. The institute should become particularly attractive to international partners later this year, when it opens what will be the world’s biggest plant for producing large volumes of clinical-grade viral vectors — used to transfer therapeutic genes into the cells of patients.
“Getting vectors is a bottleneck for us,” says Adrian Thrasher, director of the gene-therapy programme at University College London’s Institute of Child Health, and a Genethon collaborator. “Genethon’s new strategy is realistic.”
The first gene-therapy trials involved a handful of children in Italy and France who had rare and fatal immunodeficiency disorders, and showed that healthy genes could be transferred stably into patients to reverse their symptoms.
The early successes spawned a period of hype that came to an abrupt end with the 1999 death of Jesse Gelsinger, a teenager in the United States who had a profound immune reaction to his gene therapy, as well as the emergence of cancers in some immune-deficient children who had been treated. Progress has been slow and cautious ever since. More than a thousand proof-of-principle clinical studies have been done around the world (see ‘Gene promise’), and dozens have shown positive results, but as yet no form of gene therapy has been approved for routine use by the US Food and Drug Administration or the European Medicines Agency. That situation must change, according to the board of directors of the French Muscular Dystrophy Association, which created Genethon in 1990 and has funded it ever since through its annual telethons.
Although the best-known gene-therapy trials have been done in children with immune deficiencies, the technique could tackle a much wider array of diseases. Most of the current clinical studies are in cancer, with researchers trying to introduce genes that will kill the cancer cells directly, or prod the patient’s immune system into attacking them. And on 6 January, the American Society of Gene and Cell Therapy sent the director of the US National Institutes of Health a list of the diseases it believes will benefit most in the next six years from investment in translating basic research to the clinic. It included rare immunodeficiency and eye disorders, as well as more common blood disorders, two cancers and Parkinson’s disease.
Mavilio worked on the world’s first gene-therapy trial, which treated children with the immunodeficiency disorder ADA-SCID at the San Raffaele Scientific Institute in Milan. Pharmaceutical giant GlaxoSmithKline last year forged a multi-million-euro alliance with the institute to develop similar gene therapy for rare diseases, becoming the first pharmaceutical giant to invest significantly in the field.
“The disadvantage of Genethon compared to the San Raffaele is that it does not have its own hospital,” Mavilio says. “We will be very proactive in forging collaborations with top clinicians in Europe and beyond so that we can become a major hub for gene-therapy networks.”
The vector-production facility will be a huge asset for this, he says. “But it won’t be enough. To get good collaborations, we also have to be known as a force in science.” Genethon moved away from basic research in 2006, to focus on vector production. It now gets more than 90% of its money from the Telethon, but Mavilio wants this to be significantly supplemented by competitive research grants.
Philippe Moullier, director of the French national biomedical research agency’s gene-therapy unit in Nantes, and a Genethon adviser, warns that the firm needs “to remain humble and move slowly — I don’t know if we can demand to become a European hub”. Thrasher, at least, is enthusiastic about the institute’s ambitions, predicting that “Genethon will probably become our first port of call”.
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