24 October 2009 - Leber Congenital Amaurosis: gene therapy improves vision in 12 patients
“The quicker, the better” is the message promoted by the team of researchers, involved in the first clinical trials that have used gene therapy to safely restore vision in 12 patients affected by Leber Congenital Amaurosis (LCA), the most frequent cause of hereditary childhood blindness. The results of the study have been published in the journal The Lancet. Although the patients did not fully regain a normal eyesight, the treatment led to a significant improvement in visual function, in the absence of adverse events.
The project, which started in 2007, has seen the participation of three important institutes: the Telethon Institute of Genetics and Medicine (TIGEM) in Naples, the Department of Ophthalmology of the Seconda Università degli studi di Napoli (SUN), and the Children’s Hospital of Philadelphia in the USA.
The researchers have been evaluating the safety and efficacy of gene therapy over the last two years as a cure to this serious retinal disease, which affects children during the first years of life and leads to progressive visual impairment. A team of TIGEM researchers – Alberto Auricchio, Enrico Maria Surace and Sandro Banfi – has devised a “molecular strategy” to correct the defects in genes causing ocular diseases such as the RPE65 gene, considered as one of the principal actors responsible of LCA.
The clinical team at the Department of Ophthalmology, led by Francesca Simonelli, has, instead, been able to select the most suitable patients to test this innovative therapy, monitoring the patients’ clinical status at regular intervals to evaluate the safety and efficacy of the treatment. Twelve patients have been treated thus far, of which 5 were Italian patients. The surgical operation for all the patients was carried out at the Children’s Hospital of Philadelphia, under the supervision of Jean Bennett, and consisted in the injection, in the subretinal space of the eye, of a genetically engineered adeno-associated virus (AAV) carrying a normal version of the RPE65 gene.
As results from the exams carried out at regular intervals following the operation, none of the patients presented significant toxic effects, confirming the safety of the treatment. More importantly, the tests measuring visual function clearly showed that a partial visual rescue was achieved in all the patients of the sample, especially in the youngest. “This” says Francesca Simonelli “is the most important result: the earlier is the stage of the disease at which gene therapy is conducted, the higher are the possibilities that the retina of the patient is not completely compromised for it to react positively to a cure”.
An important indication for future gene therapy trials, as Alberto Auricchio underlines: “Our intention is to extend the efficacy of gene therapy not only to other forms of amaurosis but also to other ocular genetic diseases, such as Stargardt disease, for which TIGEM has already obtained orphan drug designation from the American Food and Drug Administration and from the European Medicine Agency. To this end, the eye is an ideal organ for this type of therapy, since it is small, circumscribed and immuno-privileged, which allows the administration of low drug doses and reduces the risk of reject by the immunitary system”.
Click to see article abstract
Click here to see the interview of Prof. Alberto Auricchio at the Italian TV programme “Domenica In” (Featured in YouTube)
Click here for more details from the Telethon Foundation website (in Italian)
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