Development of a therapy for Usher Syndrome


Catholic University of Sacro Cuore

Ophtalmology Institute, Policlinico A. Gemelli, Rome

The clinical unit directed by Prof. Benedetto Falsini at the Policlinico A. Gemelli in Rome is an established reference center for hereditary retinal dystrophies in Italy.
Since many years the center provides highly specialized clinical care and applies cutting-edge diagnostic methodologies.

Furthermore, it carries out research activities that focus on the investigation of potential treatments for retinal disorders, networking with other well-known research institutions both national (CNR and MAGI LAB) and international (National Eye Institute, NIH).

WithUsShare: Mario Zanobini Usher Syndrome Foundation

The “WithUsShare: Mario Zanobini Usher Syndrome Foundation” was born in 2015 by the will of Alessandro Mennella’s family. Alessandro is the grandson of Mario Zanobini and also the testimonial of the RarePartners’s programs.

The Foundation’s mission is to foster biomedical research, raise awareness and gather together as many people and organizations as possible, sharing the same goal to fight against Usher Syndrome.  



Sindrome di Usher

Usher Syndrome is a rare autosomic recessive disease characterized by hearing loss or deafness and progressive vision loss (retinitis pigmentosa).

There are three major types of Usher syndrome that are distinguished by the severity of the auditory features and by the age of onset of visual impairment.

Usher Syndrome type 1 is characterized by profound deafness from birth, balance and gait problems and retinitis pigmentosa.
Children affected by Usher Syndrome type 2 are born with moderate-to-severe hearing impairment and normal balance; retinitis pigmentosa appears between adolescence and 20 years of age.
Usher Syndrome type 3 is the less severe and children have normal hearing and balance at birth and throughout childhood and adolescence.

Retinitis pigmentosa is diagnosed between 30 and 40 years of age and simultaneously hearing and balance deteriorate. In general, retinitis pigmentosa manifests after hearing impairment and usually starts with night blindness. Vision tends to decline progressively towards complete blindness within few decades.

Today, 11 genes have been identified as responsible for Usher syndrome; all of them code for proteins that are involved in development and functioning of the ear and of the photoreceptors.

Incidence of the disease

Usher Syndrome affects 1 out of 20.000 children and about 1 out of 6 individuals diagnosed retinitis pigmentosa have Usher Syndrome. It is the most frequent cause of deaf-blindness and, in Italy, about 2.000-3.000 people are affected.  



RarePartners is thoroughly monitoring the scientific landscape of Usher Syndrome and specifically the approaches that are being undertaken to prevent/cure vision loss.
The ultimate goal will be to identify opportunities for therapy development.

Presently, there is not a cure for Usher syndrome. However, many labs worldwide are making impressive progress addressing retinal dystrophies through:

• gene therapy
• pharmacological approaches
• prosthetic implants (artificial retina).

RarePartners is currently focusing on conservative therapies that can preserve residual functional vision and so have an impact on the patient’s quality of life. Toward this aim, RarePartners has established, since 2016, a formal collaboration with the clinical and research unit led by Prof. Benedetto Falsini at the Sacro Cuore University – Policlinico A. Gemelli, Rome.
Prof. Falsini is a reference ophthalmologist for diagnosis and clinical management of Usher Syndrome.
His unit is gathering plenty of information about the natural history of the disease: a patient registry was established to collect both clinical and genetic data and now allows comparisons among patients, predictions about disease course and evolution and identification of primary outcome measures to be employed in future clinical trials.

Falsini’s unit has been also involved in exploratory studies conducted in patients with retinal dystrophies using pharmacological agents, such as for example the nerve growth factor (NGF), potentially able to slow down the retinal degeneration and even partially restore the visual acuity. This approach could be explored also in patients with Usher Syndrome.

RarePartners is committed to supporting the group of Prof. Falsini for both activities, the maintenance and enlargement of Usher patient registry and the planning of exploratory clinical trials with new therapeutic approaches.

RarePartners, together with the “WithUsShare Foundation” and the Ophthalmology Department of University of Parma (Prof. S, Gandolfi) is also supporting a long-term project project aiming at establishing a reference center for the diagnosis and cure of Usher Syndrome patients in Italy.
The first important step has been the organization and financing of a training program for Dr. Giacomo Calzetti, a young Italian Ophthalmologist, at the Hereditary Retinal Degeneration Center, Scheie Eye Institute, University of Pennsylvania, under the supervision of the Director of the Center,  Prof. Samuel G. Jacobson, an internationally recognized expert of retinal diseases and Usher Syndrome in particular.

During the period 2017-2018 RarePartners has financially supported a project aimed at the development of an innovative artificial retina currently ongoing at the laboratories of the Istituto Italiano di Tecnologia (IIT) in Genoa (Center "Synaptic Neuroscience and Technology") and Milan (Centre "Nanoscience and Technology") in collaboration with the team of ophthalmologists of the Ospedale Sacro Cuore Don Calabria of Negrar (VR).
The prototypes, developed by the laboratories of the two IIT centers led by Prof. Benfenati and Professor Lanzani, are the result of a multidisciplinary approach that exploits a technology based on the use of light-sensitive polymers.
The preliminary data obtained in experimental models are very promising and the first safety and efficacy trial in humans could be initiated very soon.