on Multiple sclerosis (Houndmills, Basingstoke, England)
by Saccà F, Lanzillo R, Signori A, Maniscalco GT, Signoriello E, Lo Fermo S, Repice A, Annovazzi P, Baroncini D, Clerico M, Binello E, Cerqua R, Mataluni G, Bonavita S, Lavorgna L, Zarbo IR, Laroni A, Rossi S, Pareja Gutierrez L, La Gioia S, Frigeni B, Barcella V, Frau J, Cocco E, Fenu G, Torri Clerici V, Sartori A, Rasia S, Cordioli C, Di Sapio A, Pontecorvo S, Grasso R, Barrilà C, Russo CV, Esposito S, Ippolito D, Bovis F, Gallo F, Sormani MP,
With many options now available, first therapy choice is challenging in multiple sclerosis (MS) and depends mainly on neurologist and patient preferences.
on European journal of neurology
by Frau J, Sormani MP, Signori A, Realmuto S, Baroncini D, Annovazzi P, Signoriello E, Maniscalco G, La Gioia S, Cordioli C, Frigeni B, Rasia S, Fenu G, Grasso R, Sartori A, Lanzillo R, Stromillo ML, Rossi S, Forci B, Cocco E,
There is debate as to whether the apparent rebound after fingolimod discontinuation is related to the discontinuation itself, or if it is due to the natural course of highly active multiple sclerosis (MS). We aimed to survey the prevalence of severe reactivation and rebound after discontinuation of fingolimod in a cohort of Italian patients with MS.
on Retina (Philadelphia, Pa.)
by Di Iorio V, Orrico A, Esposito G, Melillo P, Rossi S, Sbordone S, Auricchio A, Testa F, Simonelli F
To investigate the natural history of Stargardt disease over a multiyear follow-up.
on JCI insight
by Botta S, de Prisco N, Marrocco E, Renda M, Sofia M, Curion F, Bacci ML, Ventrella D, Wilson C, Gesualdo C, Rossi S, Simonelli F, Surace EM
The genome-wide activity of transcription factors (TFs) on multiple regulatory elements precludes their use as gene-specific regulators. Here we show that ectopic expression of a TF in a cell-specific context can be used to silence the expression of a specific gene as a therapeutic approach to regulate gene expression in human disease. We selected the TF Krüppel-like factor 15 (KLF15) based on its putative ability to recognize a specific DNA sequence motif present in the rhodopsin (RHO) promoter and its lack of expression in terminally differentiated rod photoreceptors (the RHO-expressing cells). Adeno-associated virus (AAV) vector-mediated ectopic expression of KLF15 in rod photoreceptors of pigs enables Rho silencing with limited genome-wide transcriptional perturbations. Suppression of a RHO mutant allele by KLF15 corrects the phenotype of a mouse model of retinitis pigmentosa with no observed toxicity. Cell-specific-context conditioning of TF activity may prove a novel mode for somatic gene-targeted manipulation.
on Molecular therapy : the journal of the American Society of Gene Therapy
by Maddalena A, Tornabene P, Tiberi P, Minopoli R, Manfredi A, Mutarelli M, Rossi S, Simonelli F, Naggert JK, Cacchiarelli D, Auricchio A
Retinal gene transfer with adeno-associated viral (AAV) vectors holds great promise for the treatment of inherited retinal degenerations (IRDs). One limit of AAV is its transfer capacity of about 5 kb, which can be expanded to about 9 kb, using dual AAV vectors. This strategy would still not suffice for treatment of IRDs such as Usher syndrome type 1D or Alström syndrome type I (ALMS) due to mutations in CDH23 or ALMS1, respectively. To overcome this limitation, we generated triple AAV vectors, with a maximal transfer capacity of about 14 kb. Transcriptomic analysis following triple AAV transduction showed the expected full-length products along a number of aberrant transcripts. However, only the full-length transcripts are efficiently translated in vivo. We additionally showed that approximately 4% of mouse photoreceptors are transduced by triple AAV vectors and showed correct localization of recombinant ALMS1. The low-photoreceptor transduction levels might justify the modest and transient improvement we observe in the retina of a mouse model of ALMS. However, the levels of transduction mediated by triple AAV vectors in pig retina reached 40% of those observed with single vectors, and this bodes well for further improving the efficiency of triple AAV vectors in the retina.
by Laroni A, Signori A, Maniscalco GT, Lanzillo R, Russo CV, Binello E, Lo Fermo S, Repice A, Annovazzi P, Bonavita S, Clerico M, Baroncini D, Prosperini L, La Gioia S, Rossi S, Cocco E, Frau J, Torri Clerici V, Signoriello E, Sartori A, Zarbo IR, Rasia S, Cordioli C, Cerqua R, Di Sapio A, Lavorgna L, Pontecorvo S, Barrilà C, Saccà F, Frigeni B, Esposito S, Ippolito D, Gallo F, Sormani MP,
To assess whether the presence of concomitant diseases at multiple sclerosis (MS) diagnosis is associated with the choice and the treatment persistence in an Italian MS cohort.
on International ophthalmology
by Rossi S, Santamaria C, Boccia R, De Rosa L, D'Alterio FM, Simonelli F, De Rosa G
To evaluate the clinical results of standard, transepithelial (TE) and iontophoresis (I) corneal cross-linking (CXL), in patients with progressive keratoconus.
on Ophthalmic genetics
by Testa F, Melillo P, Rossi S, Marcelli V, de Benedictis A, Colucci R, Gallo B, Brunetti-Pierri R, Donati S, Azzolini C, Marciano E, Simonelli F
To investigate the prevalence of macular abnormalities in patients affected by Usher syndrome (USH), by comparing the clinical findings between two types (i.e., USH1 and USH2).
on IEEE journal of translational engineering in health and medicine
by Melillo P, Riccio D, Di Perna L, Sanniti Di Baja G, De Nino M, Rossi S, Testa F, Simonelli F, Frucci M
Color vision deficiency (CVD) is an extremely frequent vision impairment that compromises the ability to recognize colors. In order to improve color vision in a subject with CVD, we designed and developed a wearable improved vision system based on an augmented reality device. The system was validated in a clinical pilot study on 24 subjects with CVD (18 males and 6 females, aged 37.4 ± 14.2 years). The primary outcome was the improvement in the Ishihara Vision Test score with the correction proposed by our system. The Ishihara test score significantly improved ([Formula: see text]) from 5.8 ± 3.0 without correction to 14.8 ± 5.0 with correction. Almost all patients showed an improvement in color vision, as shown by the increased test scores. Moreover, with our system, 12 subjects (50%) passed the vision color test as normal vision subjects. The development and preliminary validation of the proposed platform confirm that a wearable augmented-reality device could be an effective aid to improve color vision in subjects with CVD.
on PloS one
by Melillo P, Orrico A, Chirico F, Pecchia L, Rossi S, Testa F, Simonelli F
To develop and validate a tool aiming to support ophthalmologists in identifying, during routine ophthalmologic visits, patients at higher risk of falling in the following year.