Terapia genetica di successo...

Ricercatori dell`Universita` della Pennsylvania, in collaborazione con la Seconda Universita` di Napoli e l`istituto Telethon per la ricerca medica e genetica, hanno utilizzato una terapia genica per restituire la vista a tre giovani affetti da una rara forma di cecita` congenita. Sebbene i pazienti non abbiano riacquisito interamente la vista, i risultati preliminari aprono le porte a nuovi studi e ad innovativi trattamenti per questi disturbi della retina. I risultati, provenienti da The Children`s Hospital of Philadelphia, sono apparsi sulla rivista The New England Journal of Medicine. “Questo e` il primo trial di terapia genica in una condizione pediatrica non letale” afferma Albert M.Maguire, medico e professore associato del Department of Opthalmology presso l`Universita` della Pennsylvania, nonche` medico dell`Istituto di Oftalmologia. Maguire, insieme a sua moglie Jean Bennett, medico e professore di Oftalmologia all`Universita` Penn e Senior Investigator al F.M. Kirby Center for Molecular Ophthalmology at Penn’s Scheie Eye Institute, hanno studiato patologie degenerative genetiche alla retina come la Leber congenital amaurosis (LCA), negli ultimi 18 anni; una patologia che causa problemi ai recettori di luce della retina, che comincia con brevi perdite di vista e puo` portare alla cecita` intorno ai 20/30 anni e non c`e` ancora un trattamento di cure definitivo. “La vista dei pazienti e` migliorata tanto da riconoscere i movimenti delle mani o sino a leggere alcune righe su di un grafico”. Per far cio` e` stato utilizzato un vettore, un virus adeno-associato (AAV) geneticamente modificato per trasportare un versione normale del gene RPE65, mutato in forma di LCA. Il gene vettore e` stato costruito presso The Hospital’s Center for Cellular and Molecular Therapeutics (CCMT), mentre la terapia genica e` stata avviata sui tre pazienti presso il Children’s Hospital of Philadelphia tra l`ottobre del 2007 e il gennaio del 2008. Sui pazienti, nell`arco di sei mesi si e` anche riscontrata la diminuzione del cosiddetto nistagmo, movimento non controllato degli occhi tipico del LCA, oltre che ad un aumento significativo della percezione della luce (tanto da far muovere un paziente in un percorso ad ostacoli appositamente preparato). Lo studio e` stato sponsorizzato dal Center for Cellular and Molecular Therapeutics at The Children’s Hospital of Philadelphia, diretto da Katherine A. High, M.D. High del Howard Hughes Medical Institute.Researchers from the University of Pennsylvania have used gene therapy to safely restore vision in three young adults with a rare form of congenital blindness. Although the patients did not achieve normal eyesight, the preliminary results set the stage for further studies of an innovative treatment for this and possibly other retinal diseases. Results from the clinical trial done at The Children’s Hospital of Philadelphia appear online in The New England Journal of Medicine.“This is the first gene therapy trial for a nonlethal pediatric condition,” said Albert M. Maguire, M.D., Associate Professor, Department of Ophthalmology, University of Pennsylvania School of Medicine and a physician at The Children’s Hospital of Philadelphia. Maguire, together with his wife, Jean Bennett, M.D., Ph.D., Professor of Ophthalmology at Penn and Senior Investigator at the F.M. Kirby Center for Molecular Ophthalmology at Penn’s Scheie Eye Institute, have been researching inherited retinal degenerations such as Leber congenital amaurosis (LCA), for 18 years. LCA is a group of inherited blinding diseases that damages light receptors in the retina. It usually begins stealing sight in early childhood and causes total blindness during a patient’s twenties or thirties. Currently, there is no treatment for LCA.“Patients’ vision improved from detecting hand movements to reading lines on an eye chart,” Maguire added. In 2001, Bennett and Maguire were part of a teamwhich reported successfully reversing blindness using gene therapy on dogs affected by the same naturally occurring form of congenital blindness.The current study is sponsored by the Center for Cellular and Molecular Therapeutics at The Children’s Hospital of Philadelphia, directed by Katherine A. High, M.D. High, a study leader and an Investigator of the Howard Hughes Medical Institute, has been a pioneer in translational and clinical studies of gene therapy for genetic disease, and in 2005 initiated a collaboration with Bennett and her group to translate their exciting animal findings into a clinical study.The scientists used a vector, a genetically engineered adeno-associated virus, to carry a normal version of the gene, called RPE65, that is mutated in one form of LCA. Three patients received the gene therapy via a surgical procedure performed by Maguire between October 2007 and January 2008 at The Children’s Hospital of Philadelphia, where the gene vector was manufactured at the hospital’s Center for Cellular and Molecular Therapeutics (CCMT).Starting two weeks after the injections, all three patients reported improved vision in the injected eye. The researchers also reported that each injected eye became approximately three times more sensitive to light, and each was improved compared to the uninjected, previously better functioning eye.Testing continued over a period of six months following the gene therapy vector administration. One patient was better able to navigate an obstacle course compared to before the injection. The patients also had less nystagmus, an involuntary movement of the eyes that is common in LCA. In the patient who experienced better vision even in the uninjected eye, the researchers suggest that the reduced nystagmus benefited both eyes.“The current clinical trial will continue with more patients and with ongoing follow-up to monitor results,” said Bennett. “We expect improvements to be more pronounced if treatment occurs in childhood, before the disease progresses.”In addition to the team at The University of Pennsylvania and The Children’s Hospital of Philadelphia, the Second University of Naples and the Telethon Institute of Genetics and Medicine (both in Italy), and several other American institutions took part in the research.