Francesco Testa

Professor of Ophtalmology

Name Francesco
Surname Testa
Institution Università degli Studi della Campania Luigi Vanvitelli
Address Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy


  • AAV-mediated photoreceptor transduction of the pig cone-enriched retina.

    Publication Date: 01/07/2011 on Gene therapy
    by Mussolino C, della Corte M, Rossi S, Viola F, Di Vicino U, Marrocco E, Neglia S, Doria M, Testa F, Giovannoni R, Crasta M, Giunti M, Villani E, Lavitrano M, Bacci ML, Ratiglia R, Simonelli F, Auricchio A, Surace EM
    DOI: 10.1038/gt.2011.3

    Recent success in clinical trials supports the use of adeno-associated viral (AAV) vectors for gene therapy of retinal diseases caused by defects in the retinal pigment epithelium (RPE). In contrast, evidence of the efficacy of AAV-mediated gene transfer to retinal photoreceptors, the major site of inherited retinal diseases, is less robust. In addition, although AAV-mediated RPE transduction appears efficient, independently of the serotype used and species treated, AAV-mediated photoreceptor gene transfer has not been systematically investigated thus so far in large animal models, which also may allow identifying relevant species-specific differences in AAV-mediated retinal transduction. In the present study, we used the porcine retina, which has a high cone/rod ratio. This feature allows to properly evaluate both cone and rod photoreceptors transduction and compare the transduction characteristics of AAV2/5 and 2/8, the two most efficient AAV vector serotypes for photoreceptor targeting. Here we show that AAV2/5 and 2/8 transduces both RPE and photoreceptors. AAV2/8 infects and transduces photoreceptor more efficiently than AAV2/5, similarly to what we have observed in the murine retina. The use of the photoreceptor-specific rhodopsin promoter restricts transgene expression to porcine rods and cones, and results in photoreceptor transduction levels similar to those obtained with the ubiquitous promoters tested. Finally, immunological, toxicological and biodistribution studies support the safety of AAV subretinal administration to the large porcine retina. The data presented here on AAV-mediated transduction of the cone-enriched porcine retina may affect the development of gene-based therapies for rare and common severe photoreceptor diseases.

  • An atypical form of Bietti crystalline dystrophy.

    Publication Date: 01/06/2011 on Ophthalmic genetics
    by Rossi S, Testa F, Li A, Iorio VD, Zhang J, Gesualdo C, Corte MD, Chan CC, Fielding Hejtmancik J, Simonelli F
    DOI: 10.3109/13816810.2011.559653

    To describe clinical and functional features of a patient with Bietti crystalline dystrophy and atypical electroretinogram responses.

  • Molecular and clinical characterization of albinism in a large cohort of Italian patients.

    Publication Date: 14/03/2011 on Investigative ophthalmology & visual science
    by Gargiulo A, Testa F, Rossi S, Di Iorio V, Fecarotta S, de Berardinis T, Iovine A, Magli A, Signorini S, Fazzi E, Galantuomo MS, Fossarello M, Montefusco S, Ciccodicola A, Neri A, Macaluso C, Simonelli F, Surace EM
    DOI: 10.1167/iovs.10-6091

    The purpose of this study was to identify the molecular basis of albinism in a large cohort of Italian patients showing typical ocular landmarks of the disease and to provide a full characterization of the clinical ophthalmic manifestations.

  • Gene therapy for Leber's congenital amaurosis is safe and effective through 1.5 years after vector administration.

    Publication Date: 01/03/2010 on Molecular therapy : the journal of the American Society of Gene Therapy
    by Simonelli F, Maguire AM, Testa F, Pierce EA, Mingozzi F, Bennicelli JL, Rossi S, Marshall K, Banfi S, Surace EM, Sun J, Redmond TM, Zhu X, Shindler KS, Ying GS, Ziviello C, Acerra C, Wright JF, McDonnell JW, High KA, Bennett J, Auricchio A
    DOI: 10.1038/mt.2009.277

    The safety and efficacy of gene therapy for inherited retinal diseases is being tested in humans affected with Leber's congenital amaurosis (LCA), an autosomal recessive blinding disease. Three independent studies have provided evidence that the subretinal administration of adeno-associated viral (AAV) vectors encoding RPE65 in patients affected with LCA2 due to mutations in the RPE65 gene, is safe and, in some cases, results in efficacy. We evaluated the long-term safety and efficacy (global effects on retinal/visual function) resulting from subretinal administration of AAV2-hRPE65v2. Both the safety and the efficacy noted at early timepoints persist through at least 1.5 years after injection in the three LCA2 patients enrolled in the low dose cohort of our trial. A transient rise in neutralizing antibodies to AAV capsid was observed but there was no humoral response to RPE65 protein. The persistence of functional amelioration suggests that AAV-mediated gene transfer to the human retina does not elicit immunological responses which cause significant loss of transduced cells. The persistence of physiologic effect supports the possibility that gene therapy may influence LCA2 disease progression. The safety of the intervention and the stability of the improvement in visual and retinal function in these subjects support the use of AAV-mediated gene augmentation therapy for treatment of inherited retinal diseases.

  • Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial.

    Publication Date: 07/11/2009 on Lancet (London, England)
    by Maguire AM, High KA, Auricchio A, Wright JF, Pierce EA, Testa F, Mingozzi F, Bennicelli JL, Ying GS, Rossi S, Fulton A, Marshall KA, Banfi S, Chung DC, Morgan JI, Hauck B, Zelenaia O, Zhu X, Raffini L, Coppieters F, De Baere E, Shindler KS, Volpe NJ, Surace EM, Acerra C, Lyubarsky A, Redmond TM, Stone E, Sun J, McDonnell JW, Leroy BP, Simonelli F, Bennett J
    DOI: 10.1016/S0140-6736(09)61836-5

    Gene therapy has the potential to reverse disease or prevent further deterioration of vision in patients with incurable inherited retinal degeneration. We therefore did a phase 1 trial to assess the effect of gene therapy on retinal and visual function in children and adults with Leber's congenital amaurosis.

  • A normal electro-oculography in a family affected by best disease with a novel spontaneous mutation of the BEST1 gene.

    Publication Date: 01/11/2008 on The British journal of ophthalmology
    by Testa F, Rossi S, Passerini I, Sodi A, Di Iorio V, Interlandi E, Della Corte M, Menchini U, Rinaldi E, Torricelli F, Simonelli F
    DOI: 10.1136/bjo.2008.143776

    To describe clinical and genetic findings in an Italian family affected by Best disease.

  • Safety and efficacy of gene transfer for Leber's congenital amaurosis.

    Publication Date: 22/05/2008 on The New England journal of medicine
    by Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell'Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J
    DOI: 10.1056/NEJMoa0802315

    Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) ( number, NCT00516477 []). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA.

  • Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients.

    Publication Date: 01/09/2007 on Investigative ophthalmology & visual science
    by Simonelli F, Ziviello C, Testa F, Rossi S, Fazzi E, Bianchi PE, Fossarello M, Signorini S, Bertone C, Galantuomo S, Brancati F, Valente EM, Ciccodicola A, Rinaldi E, Auricchio A, Banfi S
    DOI: 10.1167/iovs.07-0068

    To identify the molecular basis of Leber's congenital amaurosis (LCA) in a cohort of Italian patients and to perform genotype-phenotype analysis.

  • Intrafamilial clinical heterogeneity associated with a novel mutation of the retinal degeneration slow/peripherin gene.

    Publication Date: 01/01/2007 on Ophthalmic research
    by Simonelli F, Testa F, Marini V, Interlandi E, Rossi S, Pognuz DR, Virgili G, Garrè C, Bandello F
    DOI: 10.1159/000108118

    To identify the phenotypic variations in 6 related individuals affected by a novel mutation in the retinal degeneration slow/peripherin gene.

  • Clinical phenotype of an Italian family with a new mutation in the PRPF8 gene.

    Publication Date: 01/09/2006 on European journal of ophthalmology
    by Testa F, Ziviello C, Rinaldi M, Rossi S, Di Iorio V, Interlandi E, Ciccodicola A, Banfi S, Simonelli F

    To report the clinical and functional characteristics of an autosomal dominant retinitis pigmentosa (ADRP) family with a novel point mutation (P2301S) in the PRPF8 gene.