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 Rare Partners’s program named Run4Usher.
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.  



Rare Partners 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;
  • prosthetic implants (artificial retina);
  • pharmacological approaches.

Rare Partners is currently focusing on potential more conservative therapies that can preserve residual functional vision and so have an impact on the patient’s quality of life. Toward this aim, Rare Partners signed 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 is also involved in a research study that tests neurotrophic factors for their ability to prevent or slow down degeneration of visual cells, enabling a prolonged functional vision.

Preliminary in vivo studies as well as a pilot clinical trial employing the nerve growth factor (NGF) suggested a potential efficacy of this compound for retinal dystrophies.
Currently, Falsini is considering to test this approach in patients with Usher Syndrome.
Rare Partners committed to support these activities for two years and to co-fund the positions of two scientists working on this project under the leadership of Prof. Falsini.

Rare Partners is also establishing international collaborations with other research institutions, in particular with Professor Samuel G. Jacobson, Director of the Hereditary Retinal Degeneration Center, Scheie Eye Institute, University of Pennsylvania.
Prof. Jacobson is a world expert of retinal diseases and Usher Syndrome. The feasibility of a training program for a young Italian researcher/clinician to be taken at Prof. Jacobson’s center in Philadelphia is being assessed and could possibly be achieved thanks also to the financial support of WithUsShare: Mario Zanobini Usher Syndrome Foundation.

As part of its plans for Usher Syndrome, Rare Partners organizes ad hoc meetings whose aim is to involve experts and to stimulate discussion and ideas on potential therapies for Usher syndrome. A first meeting was held on June 25, 2015 at the Dibit, Research Centre of the San Raffaele Hospital in Milan, and has seen speaker Prof. Jacobson with a lecture titled: "The road to treatment of inherited retinal degenerations: where are we now? ".