Amiloidosi da Gelsolina	P.24.149
Assonopatie sensoriali ereditarie	P.06.38
Atassia di Friedreich	P.07.42
Atassia episodica tipo II	P.07.41
Atassia Spinocerebellare 38	P.10.84
Atassia Telangectasia	P.07.40
Atrofia girata della coroide e della retina	P.16.111
Atrofia Muscolare Spinale	P.01.11 , P.04.27 , P.04.28 , P.04.29
Atrofia Muscolare Spinale di tipo 1	P.04.30
Atrofia Muscolare Spinale e Bulbare	P.04.25 , P.10.82 , P.10.83
Atrofia Ottica Dominante	P.16.109
Beta-talassemia	P.18.117 , P.18.118 , P.18.119
Cardiomiopatia Aritmogena	P.14.106
Ceroidolipofuscinosi neuronali	P.10.78
Charcot Marie Tooth di tipo 2B	P.10.63
Condrodisplasie	P.13.101
Corea di Huntington	P.10.73 , P.10.74
Deficit del Trasportatore della Creatina	P.11.86
Deficit di AGC1	P.06.33
Diabete Tipo 1, Mucopolisaccaridosi Tipo 1	P.11.94 , P.20.139
Difetti del ciclo dell'urea	P.11.96
Disabilità intellettiva	P.09.62
Disabilità intellettiva, disordini dello spettro autistico	P.09.56
Disautonomia Familiare	P.10.66
Discinesia parossistica kinesigenica	P.08.51
Disfunzione Mitocondriale	P.10.75
Disordine CDKL5	P.08.45
Disordini dello spettro autistico	P.09.52
Displasia Fibrosa	P.13.103
Displasia gnatodiafisaria	P.13.104
Distrofia dei coni	P.16.110
Distrofia di Ullrich; Distrofia di Duchenne	P.01.12
Distrofia Miotonica di Steinert	P.04.23
Distrofia Miotonica di tipo 1	P.01.9 , P.03.19
Distrofia muscolare	P.01.8
Distrofia Muscolare Congenita da deficit di Merosina	P.01.7
Distrofia Muscolare Congenita di Ullrich; Miopatia di Bethlem	P.01.13
Distrofia Muscolare dei cingoli di tipo 2D	P.01.6
Distrofia Muscolare di Duchenne	P.01.2 , P.01.3 , P.01.4 , P.01.5 , P.02.15
Distrofie Muscolari e Miopatie	P.01.1
Emicrania Emiplegica Familiare	P.06.36
Emicrania Emiplegica Familiare di tipo 3	P.06.37
Emofilia	P.18.121 , P.18.122
Emofilia A	P.18.123
Encefalopatia epilettica infantile precoce 9 (EIEE9)	P.08.48
Encefalopatia famigliare con corpi di inclusione di neuroserpina	P.10.68
Epilessia temporale laterale autosomica dominante	P.08.44
Epilessia, disabilità intelletiva	P.08.47
Fibrosi Cistica, Malattie da accumulo lisosomiale	P.22.145
GLD, MLD, GM2 Gangliosidosi	P.10.69
Glicogenosi 1b	P.11.90
Glicogenosi di tipo III	P.04.21
Glomerulosclerosi Focale Segmentaria	P.21.143
Immunodeficienza combinata da difetto RAG1	P.20.138
Immunodeficienza Comune Variabile	P.20.132
Immunodeficienze combinate e Immunodeficienza da deficit di adenosina deaminasi 2	P.20.137
Insonnia Familiare Fatale	P.10.67
Ipercolesterolemia Familiare	P.11.88
Ipercolesterolemia familiare, Emoglobinopatie	P.11.89
Ipogonadismo ipogonadotropo	P.15.108
Malattia da accumulo di lipidi neutri	P.02.17
Malattia di Alzheimer	P.10.65
Malattia di Charcot Marie Tooth di tipo 2A	P.05.31
Malattia di Creutzfeldt-Jakob	P.10.64
Malattia di Fabry	P.11.87
Malattia di Kennedy	P.04.26
Malattia di Krebbe	P.10.70
Malattia di Pompe	P.11.95
Malattia di Wilson	P.11.97 , P.19.129
Malattia Genetiche	P.28.159
Malattia Granulomatosa cronica	P.20.131
Malattia Renale Tubulointerstiziale Autosomica Dominante	P.21.142
Malattie associate a mutazioni in KCNQ	P.08.50
Malattie da prioni genetiche	P.10.81
Malattie delle line cellulari immuno-ematologiche	P.18.120
Malattie di origine genetica	P.28.158
Malattie Genetiche	P.12.98 , P.20.133 , P.28.156 , P.28.157 , P.28.160 , P.28.161 , P.28.162 , P.28.163 , P.28.164 , P.28.165 , P.28.166 , P.28.167 , P.28.168
Malattie Genetiche in generale	P.27.155
Malattie Genetiche, Sindrome di Birt-Hogg-Dubè (BHD)	P.21.144
Malattie Mitocondriali	P.04.22 , P.11.92
Malattie non diagnosticate	P.26.154
Malattie rare	P.28.169 , P.28.170
Malattie retiniche ereditarie	P.16.112
Malformazioni Cavernose Cerebrali	P.25.152 , P.25.153
Miopatia congenita central core	P.02.14
Miopatia degli Aggregati Tubulari	P.02.18
Miopatie Mitocondriali	P.02.16
Morbo di Parkinson	P.10.79
Mucolipidosi di tipo 4	P.06.39
Mucopolisaccaridosi di tipo I Hurler	P.11.93
Mucopolisaccaridosi tipo IIIA	P.10.76 , P.10.77
Neurodegenerazione associata a pantotenato chinasi (PKAN) e Neurodegenerazione associata alla proteina COASY (CoPAN)	P.10.80
Neuropatie ereditarie Charcot Marie Tooth	P.04.20
Osteopetrosi Autosomica Dominante di tipo 2	P.13.99
Osteopetrosi Autosomica Recessiva	P.13.100
Osteopetrosi e Sindrome di Bartter	P.13.105
Paraplegia Spastica Ereditaria	P.10.71
Paraplegia Spastica Ereditaria (SPG7)	P.10.72
Patologie POLG-collegate	P.04.24
Polineuropatia amiloidosica familiare	P.05.32
Pseudo-ostruzione intestinale cronica	P.17.116
Retinite Pigmentosa (RP)	P.16.113 , P.16.114
Ritardo mentale X-linked, Macroencefalia/Autismo	P.09.57
Sarcoglicanopatie	P.01.10
Sclerosi Laterale Amiotrofica	P.28.171
Sindrome da cheratite, ittiosi e sordità (KID)	P.23.148
Sindrome da delezione 22q11.2	P.06.35
Sindrome da Immunodeficienza, instabilità Centromerica, anomalie Facciali (ICF)	P.20.136
Sindrome da insufficienza congenita del midollo osseo	P.18.125
Sindrome da iper-IgM legata al cromosoma X	P.18.128
Sindrome della X-fragile	P.09.55
Sindrome di Aicardi-Goutières	P.06.34 , P.20.130
Sindrome di Barth	P.11.85
Sindrome di Beckwith-Wiedemann, Sindrome di Siver-Russell	P.15.107
Sindrome di Down	P.09.53 , P.09.54
Sindrome di Dravet	P.08.46
Sindrome di Ehlers-Danlos	P.13.102
Sindrome di Hay-Wells	P.23.146 , P.23.147
Sindrome di Hutchinson–Gilford	P.24.150
Sindrome di Iper-IgE	P.20.135
Sindrome di Joubert	P.07.43
Sindrome di Leigh, sindrome Gracile	P.11.91
Sindrome di Lowe	P.24.151
Sindrome di Omenn	P.18.126
Sindrome di Phelan McDermid o delezione 22q13	P.09.58
Sindrome di Rett	P.09.59
Sindrome di Stargardt, Amaurosi congenita di Leber di tipo 10	P.16.115
Sindrome di Tymothy	P.09.60
Sindrome di Weaver	P.09.61
Sindrome di Wiskott Aldrich	P.20.140
Sindrome HIGM	P.20.134
Spasmi infantili; Sindrome di West	P.08.49
Tecnologia di Piattaforma	P.18.127
Terapie genica con CSE, Trapianto di CSE	P.18.124
XLP-1 (Sindrome di Duncan)	P.20.141

AEC Syndrome or Hay-Wells Syndrome	P.23.146 , P.23.147
AGC1 Deficiency	P.06.33
Agel Amyloidosis	P.24.149
Aicardi-Goutières Syndrome	P.06.34 , P.20.130
Amyotrophic Lateral Sclerosis	P.28.171
Arrhythmogenic Cardiomiopathy	P.14.106
Ataxia Telangiectasia	P.07.40
Autism Spectrum Disorders	P.09.52
Autosomal Dominant Lateral Temporal Epilepsy	P.08.44
Autosomal Dominant Optic Atrophy	P.16.109
Autosomal Dominant Osteopetrosis Type 2	P.13.99
Autosomal Dominant Tubulointerstitial Kidney Disea	P.21.142
Autosomal Recessive Osteopetrosis	P.13.100
Barth Syndrome	P.11.85
Beckwith-Wiedemann Syndrome/Siver-Russell Syndrome	P.15.107
Beta-Thalassemia	P.18.117 , P.18.118 , P.18.119
CDKL5 Deficiency Disorder	P.08.45
Central Core Disease	P.02.14
Cerebral Cavernous Malformations	P.25.152 , P.25.153
Charcot Marie Tooth Disease 2A	P.05.31
Charcot Marie Tooth Hereditary Neuropathies	P.04.20
Charcot Marie Tooth Type 2B	P.10.63
Chondrodysplasias	P.13.101
Chromosome 22q11.2 Deletion Syndrome	P.06.35
Chronic Granulomatous Disease	P.20.131
Chronic Intestinal Pseudo-Obstruction	P.17.116
CMD, LGMD, FSHD, CM	P.01.1
Combined immunodeficiencies Adenosine Deaminase 2	P.20.137
Cone Dystrophy	P.16.110
Creatine Transporter Deficiency	P.11.86
Creutzfeldt-Jakob Disease	P.10.64
CVID (Common Variable Immunodeficiency)	P.20.132
Cystic Fibrosis, Lysosomal Storage Disorders	P.22.145
Diseases of immune-hematological lineage	P.18.120
Down Syndrome	P.09.53 , P.09.54
Dravet Syndrome	P.08.46
Duchenne Muscular Dystrophy	P.01.2 , P.01.3 , P.01.4 , P.01.5 , P.02.15
Ehlers Danlos Disease	P.13.102
Epilepsy, Intellectual Disability	P.08.47
Epileptic Encephalopathy Early Infantile 9 (EIEE9)	P.08.48
Episodic Ataxia Type II	P.07.41
Fabry Disease	P.11.87
Familial Alzheimer's Disease	P.10.65
Familial Amyloidotic Polyneuropathy	P.05.32
Familial Dysautonomia	P.10.66
Familial Hemiplegic Migraine	P.06.36
Familial Hemiplegic Migraine 3	P.06.37
Familial Hypercholesterolaemia	P.11.88
Familial Hypercholesterolemia, Hemoglobinopathies	P.11.89
Fatal Familial Insomnia	P.10.67
FENIB	P.10.68
Fibrous Dysplasia	P.13.103
Focal Segmental Glomerulosclerosis	P.21.143
Fragile-X Syndrome	P.09.55
Friedreich's Ataxia	P.07.42
Genetic Diseases	P.12.98 , P.28.156 , P.28.157 , P.28.158 , P.28.159 , P.28.160 , P.28.161 , P.28.162 , P.28.163 , P.28.164 , P.28.165 , P.28.166 , P.28.167 , P.28.168
Genetic Diseases in general	P.27.155
Genetic Diseases, Birt-Hogg-Dubé (BHD) Syndrome	P.21.144
Genetic Disorders	P.20.133
GLD, MLD, GM2 Gangliosidosis	P.10.69
Globoid Cell Leukodystrophy	P.10.70
Glycogen Storage Disease Type 1B	P.11.90
Glycogen Storage Disease Type III	P.04.21
Gnathodiaphyseal Dysplasia	P.13.104
Gyrate Atrophy of the Choroid and Retina	P.16.111
Hemophilia	P.18.121 , P.18.122
Hemophilia A	P.18.123
Hereditary Sensory Axonopathies	P.06.38
Hereditary Spastic Paraplegia	P.10.71
Hereditary Spastic Paraplegia Type 7 (SPG7)	P.10.72
HIGM Syndrome	P.20.134
HSC Gene Therapy, HSC Transplantation	P.18.124
Huntington's Disease	P.10.73 , P.10.74
Hutchinson–Gilford Progeria Syndrome	P.24.150
Hyper-Ige Syndrome (HIES)	P.20.135
Hypogonadotropic Hypogonadism	P.15.108
ICF Syndrome	P.20.136
Infantile Spasms (ISSX1); West Syndrome	P.08.49
Inherited Bone Marrow Failure	P.18.125
Inherited Retinal Disease	P.16.112
Intellectual Disability, Autism Spectrum Disorders	P.09.56
Joubert Syndrome	P.07.43
KCNQ-related Diseases	P.08.50
Keratitis-Ichthyosisdeafness (KID) Syndrome	P.23.148
Limb Girdle Muscular Dystrophy Type 2D (LGMD2D)	P.01.6
Lowe Syndrome	P.24.151
Mental Retardation, X-linked; Macrocephaly/Autism	P.09.57
Merosin Deficient Congenital Muscular Dystrophy	P.01.7
Mitochondria Complex III Disease	P.11.91
Mitochondrial Diseases	P.04.22 , P.11.92
Mitochondrial Disfunction	P.10.75
Mitochondrial Myopathies	P.02.16
MPSIH	P.11.93
Mucolipidosis Type 4 (MLIV)	P.06.39
Mucopolysaccharidosis I / Type 1 Diabetes	P.11.94
Mucopolysaccharidosis Type IIIA	P.10.76 , P.10.77
Muscular Dystrophy	P.01.8
Myotonic Dystrophy Type 1	P.01.9 , P.03.19
Myotonic Dystrophy Type 1, Steinert Disease	P.04.23
Neuronal Ceroid Lipofuscinoses (NCLs)	P.10.78
Neutral Lipid Storage Disease	P.02.17
Omenn Syndrome	P.18.126
Osteopetrosis and Bartter's Syndrome	P.13.105
Parkinson's Disease	P.10.79
Paroxysmal Kinesigenic Dyskinesia	P.08.51
Phelan McDermid Syndrome	P.09.58
PKAN and CoPAN	P.10.80
Platform Technology	P.18.127
Polg-Related Diseases	P.04.24
Pompe Disease	P.11.95
Prion Genetic Diseases	P.10.81
RAG1 Severe Combined Immunodeficiency	P.20.138
Rare Diseases	P.28.169 , P.28.170
Retinitis Pigmentosa (RP)	P.16.113 , P.16.114
Rett Syndrome	P.09.59
Sarcoglycanopathies (LGMD2D-F)	P.01.10
Spinal and Bulbar Muscular Atrophy (SBMA)	P.04.25 , P.04.26 , P.10.82 , P.10.83
Spinal Muscular Atrophy	P.01.11 , P.04.27 , P.04.28 , P.04.29
Spinal Muscular Atrophy Type 1	P.04.30
Spinocerebellar Ataxia 38 (SCA38)	P.10.84
Stargardt Disease, Leber Congenital Amaurosis 10	P.16.115
T Cell Mediated Diseases	P.20.139
Tubular Aggregate Myopathy	P.02.18
Tymothy Syndrome	P.09.60
Ullrich Congenital MD; Duchenne MD	P.01.12
Ullrich Muscular Dystrophy; Bethlem Myopathy	P.01.13
Undiagnosed Diseases	P.26.154
Urea Cycle Disorders	P.11.96
Weaver Syndrome	P.09.61
Wilson Disease	P.11.97 , P.19.129
Wiskott Aldrich Syndrome	P.20.140
X-linked Hyper IgM Syndrome	P.18.128
X-linked Intellectual Disability	P.09.62
XLP-1 (Duncan Syndrome)	P.20.141

Talk 1
Store-operated calcium entry (SOCE): role in skeletal muscle function and disease
Feliciano Protasi - Università degli Studi G. d'Annunzio Chieti, Pescara

Dysregulation of Ca2+ homeostasis is associated to several pathological conditions including neurodegenerative and skeletal muscle diseases. Store-operated Ca2+ entry (SOCE) is a ubiquitous Ca2+ entry mechanism, first described in non-excitable cells, that is triggered by depletion of intracellular Ca2+ stores (endoplasmic/sarcoplasmic reticulum, respectively ER and SR). SOCE is coordinated by the communication between: a) stromal interaction molecule-1 (STIM1), which acts as the Ca2+ sensor in the ER lumen, and b) Orai1, the Ca2+-permeable channel in the plasma membrane (PM). SOCE in skeletal muscle is similarly mediated by interactions between STIM1 and Orai1 channels and is proposed to limit muscle fatigue during repetitive stimulation. A reduction in SOCE activity was proposed to contribute to muscle impairment in aging and mutations in STIM1 and Orai1 have been linked to Tubular Aggregate Myopathy (TAM), an autosomal dominant muscle disease that is clinically characterized by myalgia, cramps and muscle stiffness, with or without proximal muscle weakness.
Despite the general agreement about the importance of SOCE in skeletal muscle function and disease, the precise subcellular sites of STIM1-Orai1 was not specifically investigated for about a decade. To give our contribute to this emerging field in muscle:
1. We discovered (using a combination of electron microscopy, immunofluorescence, immunogold, ex vivo muscle contractility, and Ca2+ imaging) that exercise promotes the formation of unique intracellular junctions that contain the molecular machinery required to activate SOCE (i.e. STIM1 and Orai1). We proposed that these not-previously-identified junctions function as Ca2+ entry units (CEUs), newly discovered organelles that i) promote recovery of extracellular Ca2+ during repetitive stimulation and ii) reduce/delay muscle fatigue optimizing muscle function.
2. As mutations in STIM1 and Orai1 have been linked to TAM (with the support of Telethon GGP19219), we are now investigating i) the mechanisms that lead to formation of Tubular Aggregates (TAs), and ii) the dysfunctional properties associated to their accrual in muscle fibers. With this goal in mind, we also generated new knock-in mice of the human disease (Orai1-G98S mice) and collected the first preliminary data.

Talk 2
Autophagy as a key pathogenic mechanism in COL6-related diseases and its significance for prospective therapies
Paolo Bonaldo, Dept. of Molecular Medicine, University of Padova

Collagen VI (COL6) is a distinctive extracellular matrix protein playing a remarkably major role in different cell processes [1]. At difference from other collagens, COL6 has a unique process of intracellular assembly involving multiple steps where different chains coded by separate genes give rise to large tetramers which once secreted form a branched network of beaded microfilaments in the matrix [1]. Mutations of COL6 genes are causative for a subclass of congenital muscular dystrophies with a broad spectrum of clinical symptoms, collectively known as ‘COL6-related myopathies', which include Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD) [2].
Several years ago we generated a COL6 knockout (Col6a1–/–) mouse, whose phenotypical defects confirmed that COL6 has a critical role for muscle homeostasis and mutations. This mouse represents a valuable animal model of BM and UCMD, and its detailed characterization provided valuable information on the pathophysiological mechanisms underlying COL6-related myopathies [3-6]. Thanks to Telethon support, we demonstrated that lack of COL6 leads to organelle defects, with mitochondrial dysfunction and spontaneous apoptosis in Col6a1–/– muscle fibers. These studies allowed to understand that the mitochondrial defects are associated with an increased opening of the permeability transition pore, which can be desensitized by cyclosporin A treatment, leading also to an amelioration of muscle structure and function in mice [3]. Notably, work in patients' samples revealed similar defects [7], thus opening the way for targeted therapeutic approaches in COL6-related myopathies. A pilot clinical trial with cyclosporin A in BM and UCMD patients showed beneficial effects in muscle cells, leading to increased myofiber survival and muscle regeneration [8].
In further studies aimed at dissecting the pathomolecular mechanisms underlying COL6-related diseases, we showed that the autophagic machinery is impaired in muscles of Col6a1–/– mice and BM/UCMD patients, leading to the accumulation of dysfunctional mitochondria and organelles and to the subsequent myofiber defects [4]. Remarkably, reactivation of autophagy in Col6a1–/– mice by different approaches (e.g., prolonged starvation or low-protein diet) is beneficial for myofiber homeostasis, leading to improved muscle strength [4]. A recent pilot clinical trial, based on a 1-year low protein diet, confirmed that autophagy can be reactivated in BM and UCMD patients, with beneficial effects in counteracting the decline of functional parameters [9]. The great advantage of targeting autophagy relies on the fact that it is easily tunable by dietary means or by different nutraceuticals, such as resveratrol and spermidine (Spd). Along this line, we recently demonstrated that in vivo Spd administration to Col6a1–/– mice, by either i.p. injection or supplement to drinking water, leads to a significantly improved muscle homeostasis [10].
We now aim at understanding in detail the therapeutic efficacy of oral Spd administration, by testing different doses and regimens and monitoring their efficacy in ameliorating muscle structure and strength in Col6a1–/– mice, as well as by evaluating the effects of Spd treatment in patients' derived cells. These studies will prove the efficacy of Spd and autophagy-targeted nutraceutical approaches for COL6-related disorders, also in the perspective of their combinatorial use with mitochondria-targeted agents in the quest for the most effective and safe therapeutic strategies for these life-threatening diseases.

References: [1] Cescon et al., J. Cell Sci. 2015; [2] Bönnemann, Nature Rev. Neurol. 2011; [3] Irwin et al., Nature Genet. 2003; [4] Grumati et al., Nature Med. 2010; [5] Urciuolo et al., Nature Comm. 2013; [6] Cescon et al., Acta Neuropathol. 2018; [7] Angelin et al., PNAS 2007; [8] Merlini et al., PNAS 2008; [9] Castagnaro et al., Autophagy 2016; [10] Chrisam et al., Autophagy 2015.

Talk 3
From reverse genetics to gene therapy: Duchenne muscular dystrophy Alessandra Ferlini, MD, PHD
Medical Genetics Unit, Department of Medical Sciences, University of Ferrara, Italy
Dubowitz Neuromuscular Unit, UCL, London, UK

Duchenne muscular dystrophy (DMD) is the most common childhood muscular dystrophy affecting ~ 1:5,000 live male births. Following the identification of the defective dystrophin gene in 1986 by reverse genetics, gene function, genotype/phenotype correlations and pathogenic mechanisms have been elucidated in skeletal, smooth and cardiac muscles as well as in the brain. Thanks to new high throughput methods, a DMD genetic definition is now fully achievable and represents a requirement in order to have clinical diagnosis confirmation, family planning and preventive measures and clinical trials access.
Indeed, advances in the understanding of the molecular pathways affected in DMD have led to both the development of multiple therapeutic strategies tackling different aspects of disease pathogenesis and recently, the approval of first successful drugs for this condition. Antisense oligonucleotides, stop codon reversion and gene therapy are now a reality and have a crucial role in changing the natural history of the disease and ultimately, the whole lives of DMD-affected boys. An overview of the DMD gene story from discovery to new treatments will be presented, with a look into the future of oncoming therapeutic approaches and their wide repercussions in the neuromuscular disease field.

Talk 4
Cross-fertilization between motor neuron disorders and muscular dystrophies: improving care and targeting treatments in Myotonic Dystrophy type 1
Valeria A. Sansone - Centro clinico Nemo, Milano
The NEMO Clinical Center, Neurorehabilitation Unit, University of Milan
Background: Motor neuron disorders and muscular dystrophies are characterized by common features like muscle atrophy, weakness, fatigue and motor functional limitations. However, pathways of care and management may differ in many respects to the extent that a specific approach and decision process needs to be implemented to target better care and cure. The NEMO Center is a multidisciplinary tertiary center for the care and cure of different neuromuscular disorders, the most frequent being motor neuron disorders and the muscular dystrophies. Myotonic dystrophies (DM1) represent 25% of the patients at the site. The diagnostic and management protocols are targeted for this patient population.
Aims: To discuss how cross-fertilization between motor neuron disorders and muscular dystrophies may improve care and contribute to targeted treatments in DM1 while creating the basis for trial readiness and endpoint assessments.
Methods: Ventilatory support, nutrition protocols and motor function assessments used in ALS and the muscular dystrophies will be described and the way these have been adapted to the care of DM1 patients will be discussed. Ongoing observational studies in both the adult and congenital and pediatric variants of DM1 will be presented as part of national and international networks. An update on targeted treatments and future therapeutic trials in this field will be discussed as well as the lessons learned from the experience with innovative therapies applied to the SMA field.
Clinical Relevance: DM1 is the most common form of adult muscular dystrophy and is perhaps the most variable amongst the different diseases in medicine, ranging from a congenital presentation, to a pediatric or adult onset for to a late-onset form. Multiple organs are involved, clinical presentation varies widely and death usually occurs between the 5th and 6th decade of life. There is still a significant diagnostic delay despite a blood draw is sufficient to identify a CTG repeat expansion > 50 which is associated with the disease.
Conclusions: There are upcoming drugs which may potentially target muscle tissue or the abnormal expansions. It is mandatory to identify appropriate outcome measures in preparation for clinical trials to improve care and target treatments in DM1.

Talk 5
Whose data are my data? Sharing and protecting personal health data
Sandra Courbier, Rare Barometer survey programme Senior Manager, EURORDIS, Paris
Michela Maggi, Data Protection Officer, Fondazione Telethon, Milan
Moderation by Lucia Monaco, Head, Research Impact and strategic analysis, Fondazione Telethon

Personal health data are a core resource for biomedical research, clinical care and patient management. Sharing health data with and among researchers and healthcare professionals is key to shortening the time to diagnosis, advancing knowledge on the disease, and progressing towards the identification and development of care and therapies.
This is particularly true for rare genetic diseases, which require matching and comparing data from affected people scattered across the globe, in order to take full advantage from the bioinformatics revolution.
Privacy protection, data stewardship, and compliance with legal regulations require engagement, competence and commitment by all parties involved.
This interactive session with the audience of patient representatives and researchers will address needs, concerns and expectations expressed by the patients' community, as well as the key principles of the European regulation on data privacy relevant to the management of health data in the research setting.

Talk 6
Omics approaches to improve diagnostics (and optimize treatment) for patients with mitochondrial disease
Daniele Ghezzi – Fondazione I.R.C.C.S Istituto Neurologico "C.Besta"
Mitochondrial disorders (MD) are a genetically heterogeneous group of individually rare human diseases characterized by energy deficiency due to mitochondrial dysfunction. MD may result from pathogenic mutations of the mitochondrial or nuclear DNA, affecting components or key factors of the oxidative phosphorylation system responsible for ATP production. MD typically are multi-organ diseases affecting high-energy demand tissues such as muscle, brain and liver. Their multi-system presentation, together with their complex genetic bases, makes molecular diagnosis difficult.
The introduction of next generation sequencing has dramatically improved diagnostic yield for MD. Nevertheless, about half of MD patients still remain without molecular diagnosis despite whole exome sequencing. More recently, additional “omics” approaches (whole genome sequencing, transcriptomics, proteomics) have been considered to investigate unsolved cases and have been proven to increase the percentage of genetic diagnoses, as well as to be useful for identifying new disease-genes.
Genetic confirmation of MD and the identification of the exact molecular defect are important for patients/families to remove uncertainty and end their diagnostic odyssey, to guide genetic counseling and family planning, but they can also be fundamental for treatment. Although an effective therapeutic strategy is still missing for most of MD, a growing subgroup is amenable to treatment with cofactors (e.g. riboflavin in patients with ACAD9 deficiency); a rapid and precise diagnosis is thus crucial for these subjects.
Integration of multiple “omics” data will allow a more comprehensive view of human diseases. In addition to improve diagnosis, “omics” are expected to guide treatment and will likely become the starting point for personalized medicine.

Talk 7
Mitochondrial disorders: from gene discovery to pathomechanisms and experimental therapy
Massimo Zeviani
University of Padova, Department of Neurosciences, Padova, Italy
Mitochondria are the major source of ATP that is synthesized by the respiratory chain through the process of oxidative phosphorylation (OXPHOS), a complex biochemical process carried out through the dual control of physically separated, but functionally interrelated, genomes, nuclear and mitochondrial DNAs. The genetic and biochemical intricacy of mitochondrial bioenergetics explains the extreme heterogeneity of mitochondrial disorders, a group of highly invalidating human conditions, for which no effective treatment is nowadays available. In addition to bioenergetic failure, other mechanisms are probably predominant in the pathogenesis of specific syndromes, such as alterations of cellular redox status, the production of reactive oxygen species, compromised Ca2+ homeostasis, mitochondrial protein and organelle quality control, and mitochondrial pathways of apoptosis. By investigating selected families and patients, we have identified several new disease genes, each responsible of distinct defects of the respiratory chain, mtDNA metabolism, or both, associated with paediatric or adult-onset clinical presentations. Structural analysis and the creation of ad hoc recombinant lines in yeast, flies, and mice have allowed us to dissect out the molecular consequences of the ablation or defects of some of these proteins, and their physical status in normal and disease conditions. These models have also been exploited to implement experimental therapeutic strategies, based on gene and cell replacement, or pharmacological control of mitochondrial biogenesis. For instance, coordinated increase of autophagy and lysosomal clearance based on inhibition of mTORC1 by rapamycin is effective to markedly prolong survival in OXPHOS impairment of brain or skeletal muscle. In addition, editing of mtDNA in a mutant mouse has been successfully achieved in our Unit through zinc-finger recombinant technology, opening the possibility to the controlled reduction of heteroplasmic load in vivo. Finally the use of new AAV vectors in vivo to convey therapeutic genes warrants promising developments for effectively crossing the BBB and targeting the CNS in mitochondrial encephalopathies.

Talk 8
miR-181a and miR-181b downregulation ameliorates mitochondrial-associated neurodegeneration by enhancing mitochondrial biogenesis and mitophagy
A Indrieri^{1, 2}, S Carrella¹, A Spaziano¹, A Romano¹,E Fernandez-Vizarra³, S Barbato¹, M Zeviani³, EM. Surace²,E De Leonibus¹, S Banfi¹, B Franco^{1, 2}
1 Telethon Institute of Genetics and Medicine, Pozzuoli, Italy
2 Department of Translational Medical Science, University of Naples "Federico II", Naples, Italy
3 MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, United Kingdom

Mitochondrial dysfunction underlies the pathogenesis of a variety of human neurodegenerative diseases, either directly, in the case of rare mitochondrial diseases (MDs), or indirectly, as in more common neurodegenerative disorders, such as Parkinson's disease (PD). Despite the efforts, effective therapies are still not available for these devastating conditions. We demonstrated that microRNAs miR-181a and miR-181b (miR-181a/b) regulate key genes involved in mitochondrial biogenesis and function. We also showed that these miRNAs are involved in global regulation of mitochondrial turnover in the central nervous system through the coordinated activation of mitochondrial biogenesis and mitophagy. We thus tested whether the modulation of these miRNAs could be therapeutically exploited in neurodegenerative conditions associated with primary impairment of mitochondrial activity. We first showed that miR-181a/b downregulation effectively protects neurons from cell death and significantly ameliorates the disease phenotype in different animal models of MDs, such as two medakafish models of Microphthalmia with Linear Skin Lesions, and chemical and genetic models of Leber Hereditary Optic Neuropathy1. In addition, our preliminary data also demonstrated amelioration of the disease phenotype in a mouse model of Leigh Syndrome, an often-fatal MD characterized by severe neurodegeneration. We then tested whether miR-181a/b downregulation could also be effective in chemical models of secondary mitochondrial dysfunction. To this aim we generated medakafish and murine models of PD using the neurotoxin 6-OHDA, which is widely used for this purpose. Our data demonstrate that inactivation of miR-181a/b reduces the extent of nigrostriatal dopaminergic neurons death in both models and results in improved motor performances in the mouse PD model. Altogether our results indicate that miR-181a/b act as hubs in mitochondrial homeostasis in the central nervous system. We propose these miRNAs may represent novel gene-independent therapeutic targets for a wide-range of neurodegenerative disorders caused by mitochondrial dysfunction.

1. Indrieri A, Carrella S, Romano A, Spaziano A, Marrocco E, Fernandez-Vizarra E, Barbato S, Pizzo M, Ezhova Y, Golia FM, Ciampi L, Tammaro R, Henao-Mejia J, Williams A, Flavell RA, De Leonibus E, Zeviani M, Surace EM, Banfi S, Franco B. EMBO Mol Med. 2019 May;11(5). pii: e8734. doi: 10.15252/emmm.201708734.

Talk 9
Mitochondria as signaling hubs in neurodegeneration
Beatrice D'Orsi¹, Luisa Galla^1,2, Elisa Greotti^1,2, Edward Beamer³, Mariana Alves³, Tobias Engel³, Paola Pizzo^1,2, Diego De Stefani¹, Tullio Pozzan^1,2,4 and Rosario Rizzuto<sup>1

1</sup>Department of Biomedical Sciences, University of Padova, Padova, Italy.
² Neuroscience Institute - Italian National Research Council (CNR), Padova, Italy;
³ Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
⁴ Venetian Institute of Molecular Medicine, Padova, Italy.

In Alzheimer 's disease (AD), the role of genetic mutations in the pathogenesis is firmly established, despite their role in determining neuronal dysfunction and death is still unknown. Mitochondrial Ca2+ overload has been proposed as the no-return signal triggering neuronal death, and we have demonstrated that familial AD (FAD) due to PS2 mutations favors Ca2+ transfer from the endoplasmic reticulum (ER) to mitochondria. Recently, the molecular nature of the mitochondrial Ca2+ channel was unveiled, allowing the investigation of the role of mitochondrial Ca2+ dysregulation by new genetic tools. Our final goal is to test the genuine contribution of mitochondrial Ca2+ overload to FAD pathogenesis.
To do this, we compared mRNA profiles of the neurotransmitters, cell death pathways and MCU complex (MCUC) components between wild type (WT) and PS2-N141I/APPswe (PS2APP) mouse brains, during disease progression. We included PS2KO mice to test if the hypothesis of a loss-of-function phenotype associated to FAD-PS1 mutations Cn be extended also to FAD-PS2 mutations. PCR arrays reveal an early transcriptional impairment in PS2APP and PS2KO brains, with a non-overlapping profile between them. An early remodelling of the MCU complex was also evident, with a significant up-regulation of the MCUC enhancers. Given the transcriptional remodelling of excitatory neurotransmission, cytosolic Ca2+ dynamics of hippocampal slices have been studied. An altered NMDA-induced Ca2+ signalling is evident in 1.5-month-old PS2APP and PS2KO mice. Mitochondrial Ca2+ handling is currently under investigation.
As mentioned above, we found increased mRNA levels of genes involved in cell death, together with an up-regulated expression of MCU enhancers. We manipulated MCU protein levels to investigate how mitochondrial Ca2+ handling controls neuronal death. Since only MCU+/- mice are viable and fertile with no evident phenotype, we employed primary neuronal cultures from MCU+/+ and MCU+/- mice. The latter display a decreased mitochondrial Ca2+ uptake and neuronal death in response to NMDA-induced excitotoxicity. We could not detect a decreased cell death when neurons were exposed to a milder and transient NMDA stimulus. In line with this, increasing mitochondrial Ca2+ levels by overexpressing of MCU is per se sufficient to cause neuronal death in situ and to trigger gliosis and neuronal loss in vivo. Accordingly, MCU+/- mice were more resistant to excitotoxicity in vivo, protecting neurons from kainite acid-induced injury (a model of epilepsy).
In summary, our results suggest that a substantial rearrangement of gene expression occurs early in PS2APP and PS2KO mice, especially of those involved in Ca2+ homeostasis and cell death regulation, with no evidence of a loss-of function phenotype associated to FAD-PS2 mutations. Furthermore, we provided important new insights into the role of MCU in neuronal excitotoxicity both in situ and in vivo.

Talk 10
How can C.elegans worm your way into the study of genetic diseases
Elia Di Schiavi
Institute of Bioscience and BioResources, IBBR, CNR, Naples

Studying genetic diseases in animal models has been crucial to understand human disease pathogenesis, the function played by mutated genes and to identify potential therapies. Among the most diffused animal models, invertebrates such as C.elegans, allowed rapid analyses of the molecular mechanisms leading to diseases and the identification of new potential therapeutic targets in several diseases (e.g. SMA, obesity, Huntington)(Ashrafi et al., Nature 2003; Grice et al., BioEssays 2011; Parker et al., Nature genetics 2005). Moreover C.elegans lead to the discovery of basic processes that unexpectedly became fundamental to set new strategies to cure human diseases (e.g. RNA-interference, miRNAs, apoptotic pathway). This has been acknowledged by the Nobel Prize awarding Institutions that awarded several times the prize to researchers working with C.elegans, including prizes for Medicine. The use of C.elegans as a model for human diseases provides: a) a powerful, easy and rapid system to directly assess the consequences of mutations at the organismal level, in vivo; b) the unique advantage of visualizing individual cells in living transparent animals; c) more than 70% of disease genes presenting an ortholog. Importantly, the use of C.elegans allows to strongly reducing the number of vertebrate animals used, fulfilling the 3Rs principles (Replacing the use of mammals; Reducing the number of mammals used to a minimum; Refining the way experiments are carried out). Moreover, the use of an invertebrate model has few ethical concerns for the public and for private foundations donors and is highly supported by EU (Resolution on the protection of animals used for scientific purposes, 5/05/2009) and Italian legislation (DL N°26, March 4th, 2014). These advantages together with the small dimensions (1 mm), the high rate of fertility and hermaphroditism (300 isogenic progeny per animal) and very cheap costs, have recently caused an expansion of its use also to high troughput screenings for toxicological studies (NIEHS National Toxicology Program), to improve diagnosis and care of patients with undiagnosed diseases (NIH Undiagnosed Diseases Network) and for drug discovery. The work from several C.elegans laboratories, including Telethon Grantees, will be presented to demonstrate the power of C.elegans to study genetic diseases and to show how “As incredible as it seems, future research on flies and worms will quite often provide the shortest and most efficient path to curing human disease” (Alberts, Science 2010).

Talk 11
One by one: convergence, multiplexing and single-cell resolution in the study of neurodevelopmental disorders through brain organoids

Giuseppe Testa
Università degli Studi di Milano and Istituto Europeo di Oncologia (IEO), Milano

Talk 12
Organs-on-Chips: the promises and limits of microfluidics
Diego Di Bernardo
Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli (Napoli)

Animal models recapitulate human diseases and are still necessary to transform lab-based discovery into actual therapies for patients, starting from basic research into disease mechanisms, going into proof-of-principle studies and culminating in pre-clinical studies prior to clinical trials in human patients. In the course of the presentation I will illustrate efforts ongoing world-wide to reduce the need of animal models in biomedical research, including alternative models based on organ-on-chip and organoids and their advantages and current limitations.

Talk 13
Expanding AAV transfer capacity in the retina
Alberto Auricchio, MD
Telethon Institute of Genetics and Medicine (TIGEM) and Medical Genetics, Dept. of Advanced Biomedicine, University of Naples "Federico II", Italy

Inherited retinal degenerations (IRDs) are a major cause of blindness worldwide. In vivo retinal gene therapy with adeno-associated viral (AAV) vectors has emerged as an effective and safe strategy to counteract retinal neurodegeneration associated with IRDs. Indeed the first approved gene therapy product for an ocular disease is based on AAV. However, the DNA cargo capacity of AAV vectors is limited to about 5 kb which precludes their application to IRDs due to mutations in genes with a coding sequence (CDS) larger than 5 kb, e.g. Stargardt disease or Usher syndrome type IB. To overcome this limitation, we have developed two different strategies based on the co-delivery of two AAV vectors each containing one half of a large gene CDS. In one strategy, recombination occurs between the genomes of the two AAV vectors leading to the reconstitution of a single large expression cassette. In another strategy, the two AAV vectors separately encode for the two half polypeptides of large protein which undergo protein trans-splicing mediated by split inteins which results in reconstitution of the full length protein. Advantages and limitations of each system will be discussed as well as their application to gene therapy of IRDs.

Talk 14
Targeting common cell death pathways for the neuroprotection of degenerating photoreceptors
Marigo Valeria (1), Comitato Antonella (1), Subramanian Preeti (2), Becerra, S. Patricia (2)
(1) Department of Life Sciences, University of Modena and Reggio Emilia
(2) National Institute of Health, National Eye Institute, USA

Retinitis pigmentosa (RP) is a form of retinal degeneration (RD) and a major cause for legal blindness during working age. Over 70 different genes have been associated with RP. This genetic heterogeneity has hampered the development of therapeutic interventions, but therapies based on neuroprotection, targeting common denominators activated in different forms of RD, could benefit a large cohort of patients. Pigment epithelium-derived factor (PEDF) is a natural protein in the eye with potent retinoprotective properties and high potential to be applied in retinal degeneration therapeutics.
We have characterized the molecular pathways targeted by PEDF in murine models of RP and found that PEDF acts on PMCA calcium pumps, present at the plasma membrane of rod photoreceptors, facilitating the decrease of intracellular calcium, a key player in photoreceptor cell death (1). Reduced levels of intracellular calcium limit the activation of calpains, calcium regulated proteases, that during degeneration activate Bax and the Apoptosis Inducing Factor (AIF) as triggers of photoreceptor cell death (2). We also identified a small protein domain (17 amino acids) in the PEDF molecule that mediates the neuroprotective activity of the factor (3).

Given that smaller molecules can be more permeable and facilitate delivery with limited side effects, likely caused by other regions of the entire molecule, we tested mutagenized small peptides, derived from the neurotrophic region of PEDF, that retain binding affinity for PEDF receptor but increase the neuroprotective activity. This study identified a small peptide of 17 amino acids, with a mutation in the histidine 105 into an alanine (17mer[H105A]), with enhanced neuroprotective activity compared to PEDF (3). We have delivered the 17mer[H105A] in the retina of murine models of RP via an AAV vector, a virus recently approved for gene therapy in the eye. The neuroprotective effects of intravitreal or subretinal injections of the therapeutic virus were analyzed histologically and electrophysiologically.
1. Comitato A., Subramanian P., Turchiano G., Montanari M., Becerra S.P., Marigo V. (2018) Pigment epithelium-derived factor (PEDF) hinders photoreceptor cell death by reducing intracellular calcium in the degenerating retina. Cell Death & Disease 9: 560.
2. Comitato A., Schiroli D., Montanari M., Marigo V. (2019) Calpain Activation Is the Major Cause of Cell Death in Photoreceptors Expressing a Rhodopsin Misfolding Mutation. Molecular Neurobiology, in press.
3. Kenealey J., Subramanian P., Comitato A., Bullock J, Keehan L., Polato F., Hoover D., Marigo V., Becerra S.P. (2015) Small Retinoprotective Peptides Reveal a Receptor Binding Region on Pigment Epithelium-derived Factor. Journal of Biological Chemistry 290:25241-25253.

Talk 15
Cone dystrophies and retinal degeneration from protein structures to biological networks
Daniele Dell'Orco
Department of Neurosciences, Biomedicine and Movement Sciences - Section of Biological Chemistry - University of Verona

Cone dystrophy (COD) is a severe form of retinal disorder affecting photoreceptors, the cells where the visual signal originates. Common symptoms include decreased central and color vision and photophobia. In several patients, cone degeneration is followed by that of rods (CORD), which results in the progressive loss in peripheral vision. Currently, no cure exists for CORD, which affects 1 in 40,000 people. To date, up to 20 missense mutations in GUCA1A, the gene encoding the calcium sensor guanylate-cyclase-activating protein (GCAP1) have been associated with autosomal dominant COD/CORD. The consequence of alterations in GCAP1 have been only partly explored and mechanisms leading to the onset of the disease remain largely unclear, although a connection with the dysregulation of intracellular cGMP and Ca2+ homeostasis has been established. Human GCAP1 variants associated with COD/CORD and their interaction with the target GC were thoroughly characterized by biochemical, biophysical and electrophysiological approaches, which have all been integrated by computer simulations. Under physiological conditions GCAP1 presents a dynamic monomer-dimer equilibrium that renders its crystallization process particularly tricky. SAXS studies corroborated by protein docking simulations allowed the building of a three-dimensional model of the GCAP1 dimer. A thorough structural and functional characterization was performed of the previously known COD-associated variants affecting the Ca2+ binding sites, namely p.E155A/G and p.D100G. All variants show a constitutive activation of the GC target at physiological concentrations of Ca2+ and altered affinity for Ca2+. Finally, a novel GCAP1variant (p.E111V) associated with a severe form of CORD has been identified in an Italian family and the protein has been fully characterized.
Nano-sized liposomes with lipid composition mimicking that of photoreceptor outer segment were produced and their biodistribution was investigated in mouse retina both ex-vivo and following intra-vitreal injections. The liposomes fuse with retinal membranes and reach all layers including photoreceptor outer segments. When encapsulated with E111V-GCAP1 and delivered in vivo and ex vivo, liposomes perturbed the photoresponses of mouse photoreceptors in a way consistent with numerical simulations of the phototransduction cascade, thus opening the way to powerful tools for testing protein therapeutics hypotheses based on in vivo delivery of recombinant wild-type protein.

Talk 16
Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy
Luca Scorrano – University Padova

In Autosomal Dominant Optic Atrophy (ADOA) caused by mutations in the mitochondrial cristae biogenesis and fusion protein Optic Atrophy 1 (Opa1), retinal ganglion cell (RGC) dysfunction and visual loss occur by unknown mechanisms. Here we show an unexpected role for autophagosome accumulation at RGC axonal hillocks in ADOA pathogenesis. Expression of mutated Opa1 in RGCs causes heterogenous mitochondrial dysfunction and triggers AMPK- and tubulin acetylation dependent autophagosome accumulation at axonal hillocks, reducing axonal mitochondrial content. Pharmacological or genetic inhibition of this pathway restores axonal mitochondrial content and curtails apoptosis caused by mutated Opa1. In C. elegans, deletion of AMPK or of key autophagy genes rescues axonal mitochondrial content reduced in neurons where mitochondrial dysfunction was induced. In conditional, RGC specific Opa1-deficient mice, depletion of the essential autophagy gene Atg7 normalizes the excess autophagy and corrects the visual defects caused by Opa1 ablation. Thus, axonal hillock accumulation of autophagosomes is a conserved mechanism crucial for ADOA pathogenesis.

Fondazione Telethon e le Associazioni di pazienti: un percorso insieme
Francesca Pasinelli – Direttore Generale di Fondazione Telethon

Telethon nasce nel 1990 dalla volontà di una comunità di pazienti e familiari, assumendosi un ruolo di responsabilità sociale, dove la valorizzazione della ricerca coincide con la valorizzazione del paziente.
Il progetto collettivo che porta avanti da allora, si fonda su un ecosistema in cui cooperano diversi portatori di interesse, che condividono valori e intenti per un comune obiettivo: la cura delle malattie genetiche rare.
A guidare l'operato della Fondazione è la volontà di far sì che i pazienti si sentano garantiti da una ricerca di qualità, che i donatori sappiano come sono investiti i loro soldi e che i ricercatori siano valutati e sostenuti per competenza e impegno.
Per assicurare il mantenimento di un corretto equilibrio tra questi diversi attori, Telethon garantisce la trasparenza e l'autonomia di ciascun soggetto rispetto agli altri, in tre ambiti fondamentali: nel sistema di finanziamento (che assicura la giusta distanza tra chi chiede, chi decide e chi eroga), nelle strategie operative (dove nessuna pressione politica o commerciale deve condizionare le scelte e gli obiettivi), nel rispetto delle regole della scienza (che impongono qualità, rigore, pazienza e costante confronto internazionale, evitando le promesse di soluzioni miracolose e immediate).
Fondazione Telethon mira quindi alla creazione di alleanze e di partnership coi pazienti, con le aziende farmaceutiche e con le istituzioni regolatorie, cercando di ampliare sempre di più il tavolo di lavoro e creando un modello condiviso da parte di tutti gli attori, per ottimizzare il processo e definire modalità efficaci che permettano anche di gestire fattori limitanti (quali tempo e denaro). Vuole infatti trovare terapie e renderle sostenibili, per entrare in una dimensione fattuale dove, negoziando adozioni di un nuovo sviluppo regolatorio, si possa ridurre il percorso necessario per arrivare alla diagnosi, all'individuazione delle terapie e alla loro messa a disposizione dei pazienti, pur mantenendo inalterata la qualità.

Eccellenza, trasparenza e innovazione: le tre caratteristiche della ricerca da finanziare
Manuela Battaglia – Direzione Scientifica di Fondazione Telethon

Fondazione Telethon è un ente senza scopo di lucro - riconosciuto dal Ministero dell'Istruzione, dell'Università e della Ricerca - che si impegna ogni giorno per fare avanzare la ricerca biomedica verso la cura delle malattie genetiche rare che, proprio per la loro rarità, sono trascurate dai grandi investimenti pubblici e industriali.
Per essere efficace la Fondazione basa la propria strategia su un metodo rigoroso per selezionare le migliori idee, sostenere le attività di ricerca e tradurre i risultati raggiunti in vantaggi concreti per i pazienti. A questo processo è applicato un sistema certificato di gestione della qualità che rappresenta un modello unico tra gli Enti che finanziano ricerca in Italia.
Fondazione Telethon utilizza un metodo di finanziamento che si basa sulla valutazione dell'eccellenza scientifica affidata ad un gruppo di esperti di caratura internazionale: un gruppo di 30 ricercatori (i.e., la commissione medico scientifica) che si avvale a sua volta dell'aiuto specialistico di oltre 8000 scienziati. Fondazione Telethon, con l'impiego di una squadra dedicata in modo permanente, garantisce competenza e indipendenza nella gestione del processo di valutazione. L'elevata qualità scientifica della ricerca finanziata da Fondazione è provata dai risultati scientifici finora ottenuti che sono riconosciuti a livello internazionale e che hanno avuto un impatto decisivo sulla vita di pazienti provenienti da tutto il mondo. Questi risultati concreti confermano anche la bontà dei sistemi di selezione adottati.
Grazie al modello implementato, oggi Fondazione Telethon è riconosciuta come una delle realtà che contribuisce a livello internazionale all'avanzamento della ricerca biomedica sulle malattie genetiche rare. Non esistono scorciatoie in ricerca: la creazione di competenze uniche e processi trasparenti e di qualità sono fondamentale per il raggiungimento della cura.

Valorizzazione del percorso e dei risultati della ricerca
Annamaria Merico – Trasferimento Tecnologico di Fondazione Telethon
Simona Varani – Proprietà Intellettuale di Fondazione Telethon

Università, ospedali e centri di ricerca conducono ricerche che generano invenzioni rivoluzionarie, salvano vite e migliorano il modo in cui viviamo e lavoriamo tutti i giorni. Il trasferimento tecnologico ha un ruolo fondamentale nel condurre queste idee dal laboratorio al mercato: richiede competenze specifiche affinché le scoperte sviluppate nelle accademie vengano protette e tramite accordi con l'industria generino prodotti e servizi. Alcune invenzioni hanno successo, altre no; alcune vengono trasferite ad industrie esistenti, altre portano alla creazione di nuove aziende, che a loro volta portano alla creazione di nuovi posti di lavoro e ad un circolo virtuoso di innovazione. Vi sono vari passaggi chiave e sfide in questo processo: averne consapevolezza per chi lavora o ha interesse nell'ambito della ricerca facilita il processo e favorisce il successo.

Di chi sono i miei dati? La condivisione e la protezione dei dati sanitari personali
Sandra Courbier – Eurordis, Paris
Michela Maggi – Data Protection Officer (DPO) di Fondazione Telethon
Lucia Monaco – Responsabile Centro Studi di Fondazione Telethon

I dati sanitari personali sono una risorsa centrale per la ricerca biomedica, l'assistenza clinica e la gestione del paziente. La condivisione dei dati sanitari con e tra ricercatori e professionisti sanitari è indispensabile per abbreviare i tempi della diagnosi, per l'avanzamento della conoscenza sulla malattia e per i progressi nell'identificare e sviluppare trattamenti e terapie.
Questo è particolarmente vero per le malattie genetiche rare, che richiedono il collegamento e il confronto di dati da pazienti sparsi in tutto il globo per poter beneficiare appieno della rivoluzione bioinformatica.
La protezione della privacy, la gestione dei dati e l'applicazione delle norme di legge necessitano di coinvolgimento, competenza ed impegno da tutti gli attori interessati.
Questa sessione interattiva con il pubblico dei rappresentanti dei pazienti e dei ricercatori affronterà i bisogni, le preoccupazioni e le aspettative espressi dalla comunità dei pazienti, come pure i principi del regolamento europeo sulla privacy rilevanti per la gestione dei dati sanitari in contesto di ricerca.

Biobanche: avvertenze e modalità d'uso
Luca Sangiorgi - Coordinatore Reti Biobanche di Fondazione Telethon

La presentazione, mutuando l'impostazione di un bugiardino per farmaci, illustrerà la descrizione (principio attivo), destinazione d'uso, modalità d'uso, posologia, controindicazioni, interazioni e tutti gli effetti indesiderati sperimentalmente raccolti e segnalati dagli utilizzatori di biobanche e registri nel mondo delle malattie rare.

Per uscire dal buio: il progetto Malattie senza diagnosi
Vincenzo Nigro – Partner fondatore del progetto "Malattie senza diagnosi"
Angelo Selicorni – Partner fondatore del progetto "Malattie senza diagnosi"

Per dare una risposta a pazienti senza diagnosi e iniziare a colmare questo bisogno Telethon ha ideato il programma "Malattie Senza Diagnosi"
Nonostante i numerosi sforzi della comunità medico-scientifica e i progressi dell'analisi del Dna, esistono ancora migliaia di malattie genetiche rarissime e con cause sconosciute che rimangono non diagnosticabili. Secondo Orphanet, a fronte di oltre 7500 malattie rare conosciute (l'80% delle quali di origine genetica), sono disponibili test diagnostici soltanto per circa 4200 di esse.
È proprio per colmare questo bisogno che Telethon ha avviato questo programma, che coinvolge una rete di centri clinici italiani di riferimento per la genetica medica e un centro di ricerca, l'Istituto Telethon di genetica e medicina di Pozzuoli, dalla consolidata esperienza nelle tecniche di sequenziamento di nuova generazione (Next Generation Sequencing). Ottenere una diagnosi è il punto di partenza per chiunque soffra di una malattia genetica: permette di dare un nome alla propria malattia, di individuare altri casi simili nel mondo da cui dedurre come evolverà, ma anche di avere più informazioni per gestire sia la quotidianità sia le situazioni di emergenza, e programmare controlli medici adeguati.
Essere coinvolti in questo programma rappresenta un'opportunità in più per chi oggi non ha una diagnosi: con quasi 700 casi ricevuti, ad oggi abbiamo identificati i geni causativi in circa il 40% dei pazienti coinvolti, con una resa diagnostica paragonabile a quella di altri programmi internazionali. È tuttavia probabile che le percentuali di successo aumentino progressivamente nel corso degli anni grazie agli avanzamenti della ricerca biomedica e attraverso la rianalisi periodica dei dati. Inoltre, le informazioni ottenute sono conservate nel database del progetto: è quindi possibile che una risposta possa arrivare successivamente, grazie al confronto con dati presenti in altri database internazionali.