The best results of Telethon Italy scientific research

The best scientific results

Since 1990, thanks to the generosity and efforts of the Italians, the Telethon financed researchers have contributed towards furthering knowledge on the causes and possible therapies of genetic diseases.

The road leading to a cure of a genetic disease is very long; it can be pictured as a series of 5 steps, the first of which is the detection of the genetic defect which causes the disease. On the second step the altered disease genes are more fully investigated, with the aim of understanding their normal function in the organism and their mechanisms, which, if altered, lead to the disease.

Thanks to this information, strategies such as new drugs or gene therapies can be planned, which compensate the defect, and their efficacy is tested in cellular models (the third step) or animals (the fourth step). Finally, and only when a therapy has been proved efficient in animals, can we rise to the fifth step, clinical studies. In this phase the cure is experimented on larger and larger groups of patients to evaluate its safety and efficacy.

The diseases on the highest Telethon research steps are:

SCID-ADA: this was the first genetic disease in the world to be cured through gene therapy. The cure was defined at Hsr-Tiget in Milan and its first success was in 2002. Since then thirteen affected children have been completely cured thanks to this therapy. At present the protocol for the cure is being registered at the international regulatory authorities.

Charcot Marie-Tooth disease: a series of clinical experiments funded by Telethon has just finished at the Istituto Neurologico “Carlo Besta” in Milan. The study, involving 8 national research centres, was aimed at evaluating the efficacy of ascorbic acid (vitamin c) in the treatment of the 1A form of the disease, based on the favourable results obtained in the animal model. Vitamin C favours the formation of myelin and seems able to reduce the excessive expression of the PMP22 protein, which is the cause of the CMT1A disturbance. The results will be available very soon.
Leber congenital amaurosis: a clinical trial of gene therapy at the Children's Hospital of Philadelphia has been running since 2007 for one of the forms of this type of hereditary blindness (due to a mutation in the RPE65 gene), which also involves Tigem and the Seconda Università di Napoli. As of today, the results obtained in 12 patients (5 of which are Italian) are very positive; the treatment is safe and able to restore part of the visual capacity of the patients, especially if started early.
Marfan syndrome: a clinical study was started in 2008 to evaluate the efficacy of a new combination of drugs in the prevention of the principal risk for those suffering from this genetic disease which affects the scaffolding of our body; the breakage of the aorta. Preventing the breakage of the body’s most important blood vessel could have an enormous impact on the quality of life of these patients.
Pompe Disease: at Tigem in Naples a new therapeutic approach has been defined to this serious metabolic disease of genetic origins which affects muscles, and in particular the heart; it has been demonstrated in the animal model that adding “helper” drugs to the substitutive enzymatic therapy, which has been available for a few years, notably improves its efficacy. In light of these results, an experiment of this combined therapy in man is starting.

Metachromatic Leukodystrophy: The first clinical trial of gene therapy for this serious metabolic disease is about to start at the Hsr-Tiget, in light of the positive results obtained in the animal model.

Wiskott-Aldrich Syndrome: The first clinical trial of gene therapy for this serious immune system disease is about to start at the Hsr-Tiget, in light of the positive results obtained in the animal model.
Bethlem myopathy, Ullrich congenital muscular dystrophy: the administration of cyclosporin A, a drug which has been shown as able to cure this disease in the animal model, has generated promising results. In a pilot study, the drug stimulated the muscular regeneration in a small number of patients. At present the researchers are working on the design of a clinical study; a drug analogous to cyclosporine A has been demonstrated in the laboratory to have the same therapeutic effect, but without the side effects. A clinical trial in man is moving closer.
Duchenne muscular dystrophy: at present preclinical studies are underway to evaluate the efficacy of different therapeutic approaches to this serious neuromuscular disease, from cell therapy to drug therapy (with deacetylase inhibitors, inhibitors of myostatin), besides the so-called exon-skipping technique. Even though it is too early for information regarding its efficacy, it is understood that the best therapy will probably be a combination of those already available.
Mucopolysaccharidosis, type II: this disease has been completely cured at Tigem in Naples through gene therapy in the animal model; thanks to a particular type of vector and approach the researchers were able, for the first time, to cure the principle symptoms of the disease, including those of the brain. This is an essential step in view of transferring these results into humans.
Limb-girdle muscular dystrophy, type IIF: in an affected hamster just two injections, six months apart, of a vector containing the corrected gene is enough to cure the disease for the entire life of the animal. At Tigem in Naples researchers are now much closer to an experimentation of the therapy in humans.
Beta-thalassemia: the efficacy of gene therapy in the animal model of intermediate and major thalassemia has been confirmed at Hsr-Tiget in Milan. At present the studies are being concentrated on the evaluation of the genetic correction obtained in the laboratory on bone marrow cells drawn from thalassemic patients, in view of a future clinical trial in humans.
Factor VII deficiency: the efficacy of a highly innovative therapeutic approach to the cure of this hereditary defect of blood coagulation has been demonstrated in the laboratory. By administrating a small Rna segment we can “deceive” the cellular mechanism which produces proteins, making it work correctly even in the presence of the genetic defect.