Rare Diseases and Orphan Drugs: from genes to personalized medicine

Università degli Studi di Bari “Aldo Moro”Palazzo Ateneo – Salone degli Affreschi

Piazza Umberto I, 1 – Bari

October 10 – 11, 2016

Organizing Committee:

Diana ConteAnnamaria De Luca Jean-François DesaphyDomenico TricaricoMarcello Diego LogranoGiuseppina Annicchiarico

Organizing secretariat Local Scientific Committee:

Sabata Pierno Antonella LiantonioPaola ImbriciMichela De BellisAntonietta MeleGiulia Maria Camerino

Fulvia LorussoAlfredo Mondelli Sassinoro

Dipartimento di Farmacia-Scienze del FarmacoDipartimento di Scienze Biomediche

e Oncologia Umana

Con il patrocinio di

PROGRAM

Monday, October 10

15:30 – 16:00 Welcome reception and registration

16:00 – 16:30 Opening and Meeting PresentationAntonio Felice Uricchio, Giorgio Cantelli Forti, Roberto Perrone, Loreto Gesualdo, Diana Conte

17:00 – 18:30

18:30 – 19:00 Coffee Break and Poster View

19:00 – 19:45 Keynote Lecture I: Alfred L. George JrProfessor and Chair of PharmacologyNorthwestern University, Chicago, USA

Welfare, Funding and Patients Associations: words and aimsGiuseppina Annicchiarico, Anna Ambrosini, Graziella De Martino

16:30 – 17:00

‘Therapeutic Targeting of Ion Channels in Genetic Epilepsy’

Chair: Giorgio Cantelli Forti

Oral Comunications – Session #1Chairs: Alessandro Mugelli, Michael Pusch

Characterization of the biochemical, functional and pharmacological properties of KCNT1channels incorporating mutations causing Malignant Migrating Partial Seizures of Infancy (MMPSI)M.V. Soldovieri, F. Rizzo, P. Ambrosino, I. Mosca, L. Manocchio, G. Coppola, A. Weisz, M. Taglialatela

Electrophysiological characterization of Purkinje neurons from FHM3 (SCN1A) knock-in miceI. Zanardi, S. Bertelli, N. Plesnila, T. Freilinger, P. Gavazzo, M. Pusch

Trimethylangelicin (TMA) interacts directly with F508del-CFTR protein and rescues the F508delCFTR-dependent chloride secretionO. Laselva, M. Favia, L. Guerra, B. Di Benedetto, S. Cannone, S. Molinski, C.E. Bear, V. Casavola

The efficacy of late sodium current blockers in hypertrophic cardiomyopathy is dependent ongenotype: a study on transgenic mouse models with different mutations.R. Coppini, L. Santini, L. Mazzoni, C. Ferrantini, F. Gentile, JM. Pioner, L. Sartiani, V. Bargelli, C.Poggesi, A. Mugelli, E. Cerbai

Novel pharmacological approach to address personalized therapy in Myotonia Congenita:potential chaperone activity of 9-AC and NFA on hClC-1 channel mutants.C. Altamura, P. Imbrici, A. Toscano, R. Mantegazza, M. Lo Monaco, C. Camerino, M.R. Carratù, G.Mangiatordi, O. Nicolotti, D. Conte, J-F. Desaphy

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Tuesday, October 11

8:45 – 10:15

10:15 – 11:00 Keynote Lecture II: Dominic Wells Professor in Translational MedicineThe Royal Veterinary College, London (UK)

11:00 – 12:00 Coffee Break and Poster Discussion

Chairs: Antonio Frigeri, Domenico Tricarico, Jean-François Desaphy

Oral Comunications – Session #2

Chairs: Pierluigi Canonico, Maria Rosaria Carratù

‘Progress and problems in developing treatments for rare diseases: the lesson from Duchenne muscular dystrophy’

Chair: Angelo Vacca

Long-term evaluation of low-dose intravenus bevacizumab in hereditary hemorrhagictelangiectasiaP. Suppressa, P. Lastella, G.M. Lenato, M. Gaetani, M.L. Cavallo, C. Sabbà

5-HT7 receptor activation as a novel therapeutic strategy in fragile-X syndomeE. Lacivita, L. Costa, L.M. Sardone, M. Spatuzza, M. Niso, C.M. Bonaccorso, S. D’Antoni , M.V.Catania, L. Ciranna, M. Leopoldo

Impaired Mitochondrial Biogenesis in Limb Girdle Muscular Dystrophy 2D: EpigeneticModifications of the PGC-1α Promoter and Identification Of Nitric Oxide-Dependent SalvagePathwayM. Giovarelli, S. Pambianco, C. Perrotta, PL. Puri, S. Zecchini, D. Cervia, I. Di Renzo, L. Latella, E.Clementi, C. De Palma

Cross-talk between inflammation and metabolic failure in animal models of Duchenne musculardystrophy and idiopathic polymyositis: effects of metabolic modulatorsP. Mantuano, R.F. Capogrosso, A. Cozzoli, A. Giustino, F. Sanarica, M. De Bellis, G.M. Camerino, K.Nagaraju, A. De Luca

CFTR correctors for the treatment of type 2D Limb Girdle Muscular DystrophyM. Carotti, E. Bianchini, C. Fecchio, R. Betto, R. Sacchetto, I. Richard, D. Sandonà

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12:00 – 13:30

Concluding RemarksAnnamaria De Luca, Giorgio Cantelli Forti

13:30 – 14:00

14:00 – 15:00 Light lunch

Oral Comunications – Session #3

Chairs: Luigia Trabace, Antonio Musarò

Potential therapeutic effect of beta3-adrenergic receptor agonists on Xlinked NephrogenicDiabetes InsipidusG. Procino, M. Carmosino, S. Milano, M. Dal Monte, G. Schena, M. Mastrodonato, A. Gerbino, P.Bagnoli, M. Svelto

The role of autoimmunity in the phenotype of inherited epidermolysis bullosa patients: thecytokine profileM.G. Morgese, S. Esposito, G. Lopalco, M. Lattarulo, M. Tampoia, D. Bonamonte, L. Brunetti, A.Vitale, G. Lapadula, L. Trabace, L. Cantarini, F. Iannone, G. Annicchiarico

Targeting Calcium Sensing Receptor with calcimimetics as possible therapeutic target inAutosomal dominant polycystic kidney disease (ADPKD).A. Di Mise, G. Tamma, M. Ranieri, M. Centrone, GC Baldelli, D. Mekahli, E. N.Levtchenko, G. Valenti

New insight in pathomechanism of Pseudoxanthoma elasticumR. Miglionico, A. Ostuni, M. Armentano, L. Milella, E. Crescenzi, M. Carmosino, F. Bisaccia

New insights from massive transcriptome sequencing for motor neuron degeneration inamyotrophic lateral sclerosisAM. D’Erchia, C. Manzari, D. S. Horner, M. Chiara, I. Aiello, F. Mastropasqua, C. Lionetti, F. Pisani,GP. Nicchia, M. Svelto, E. Picardi, G. Pesole

Tuesday, October 11

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KEYNOTE SPEAKERS

SPEAKERS

AUTHORITIES and CHAIRS

Alfred L. George JrProfessor and Chair of Pharmacology

Northwestern University,

Chicago, USA

Dominic WellsProfessor in Translational Medicine

The Royal Veterinary College,

London (UK)

Italia Aiello

Concetta Altamura

Sara Bertelli

Marcello Carotti

Raffaele Coppini

Annarita Di Mise

Matteo Giovarelli

Enza Maria Lacivita

Onofrio Laselva

Paola Mantuano

Rocchina Miglionico

Serena Milano

Maria Grazia Morgese

Maria Virginia Soldovieri

Patrizia Suppressa

Antonio Felice UricchioRector of the University of Bari

Giorgio Cantelli FortiPresident of the Italian Pharmacological Society (SIF)

Roberto PerroneDirector of the Department of Pharmacy – Drug Sciences, University of Bari

Loreto GesualdoDirector of the School of Medicine, University of Bari

Diana ConteProfessor of Pharmacology, University of Bari

Anna AmbrosiniResearch Program Manager, Telethon Foundation

Giuseppina AnnicchiaricoDirector of Reginal Coordination of Rare Diseases-CO.RE.MA.R, Apulia

Pierluigi CanonicoProfessor of Pharmacology, University of Piemonte Orientale

Maria Rosaria CarratùProfessor of Pharmacology, University of Bari

Annamaria De LucaProfessor of Pharmacology, University of Bari

Graziella De MartinoPresident of “Miotonici in Associazione” (M.i.A) Onlus

Jean-François DesaphyProfessor of Pharmacology, University of Bari

Antonio FrigeriProfessor of Physiology, University of Bari

Alessandro MugelliProfessor of Pharmacology, University of Firenze

Antonio MusaròProfessor of Histology and Medical Embryology, University of Rome

Michael PuschDirector of Biophysic Institute, CNR, Italy

Luigia TrabaceProfessor of Pharmacology, University of Foggia

Domenico TricaricoProfessor of Pharmacology, University of Bari

Angelo VaccaProrector of the University of Bari, Professor of Internal Medicine 5

1. The expression of Lamin A mutant R321X leads to endoplasmic reticulum stress withaberrant Ca2+ handling. Carmosino M, Gerbino A, Schena G, Procino G, Miglionico R, ForleoC, Favale S, and Svelto M (Potenza-Bari).

2. Amyotrophic Lateral Sclerosis: modification of biophysical properties and geneexpression in skeletal muscle of a SOD-1 related mouse model. Fonzino A, Conte E,Liantonio A, Camerino GM, Mele A, Tricarico D, Dobrowolny G, Musarò A, Conte Camerino D,and Pierno S (Bari-Roma).

3. Growth hormone secretagogues protect by mitochondrial dysfunctions induced inskeletal muscle of rat model of cachexia. Sirago G, Fracasso F, Liantonio A, Conte E,Camerino GM, Torsello A, Fehrentz J-A, Martinez J, Pesce V, and Cantatore P (Bari-Milano-Montpellier).

4. Pharmacological study of SCN4A mutations located in the hNav1.4 sodium channel fastinactivation machinery to address precision medicine in non-dystrophic myotonias.Farinato A, Altamura C, Imbrici P, Maggi L, Mantegazza R, Filosto M, Ricci G, Siciliano G, LoMonaco M, Conte Camerino D, and Desaphy J-F (Bari-Milano-Pisa-Brescia-Roma).

5. Resveratrol and IbTX irreversible block BKCa channel and induce cell cycle arrests inhuman neuroblastoma SHSY5Y cells: possible use in neuroblastoma diseases. Maqoud F,Mele A, Angelelli C, Pannunzio A, Camerino C, Campanella F, Coluccia M and Tricarico D(Bari).

6. Infantile spasms and encephalopathy without preceding neonatal seizures caused byKCNQ2 R198Q, a gain-of-function variant. Miceli F, Millichap JJ, Tran B, Keator C, Joshi N,De Maria M, Soldovieri MV, Ambrosino P, Shashi V, Mikati M, Cooper EC, and Taglialatela M(Napoli-Chicago-Houston-Fort Worth-Campobasso-Durham).

7. Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) secondary to anactivating mutation in the vasopressin type 2 receptor: evidence for vasopressinindependent increase in AQP2 trafficking and osmotic water permeability. Ranieri M,Tamma G, Pellegrino T, Valenti G and Cotecchia S (Bari).

8. In vivo and in vitro pharmacological inhibition of Src Tyrosin Kinase and NADPHOxidase to counteract oxidative stress in Duchenne muscular dystrophy. Sanarica F,Cozzoli A, Capogrosso RF, Mantuano P, Cutrignelli A, Giustino A, De Bellis M, Denora N, andDe Luca A (Bari).

9. Pharmacovigilance database search discloses CLC-K channels as a novel target of theAT1R blockers Valsartan and Olmesartan. Imbrici P, Tricarico D, Mangiatordi GF, Nicolotti O,Lograno MD, Conte D, and Liantonio A (Bari).

10. Study of the expression profile and pharmacological role of the CB1 receptor inDuchenne Muscular Dystrophy (DMD) muscles: a new opportunity to reinforce musclerepair and locomotor activity. Iannotti FA, Pagano E, Adinolfi S, Guardiola O, Gazzerro E,Capasso R, Minchiotti G and Di Marzo V (Genova-Napoli).

POSTER COMMUNICATIONS

Tuesday, October, 11, 11.00-12.00

Session 1 - Chair: Antonio Frigeri

Session 2 - Chair: Domenico Tricarico

11. Digital registry SIMaRRP: a useful tool for the epidemiological analysis of raredisease in Apulia. Cetrone M, Gargano M, Fiorita T, Natale M, Malerba M, and AnnicchiaricoG (Bari).

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12. Management of common variable immunodeficiency with subcutaneous IgG selfadministration during pregnancy – a case report. Marasco C, Venturelli A, Rao L, CarratùMR, and Vacca A (Bari).

13. A spike at tumor onset earmarks low level instability in peripheral blood cells fromlynch syndrome patients. Lastella P. Lenato GM, Loconte DC, Bozzao C, Patruno M, RecchiaA, Varvara D, Piglionica M, Resta N, Suppressa P, Resta F, Sabbà C, and Stella A (Bari).

14. A case of hypogonadotropic hypogonadism associated with hereditary hemorrhagictelangiectasia. Lenato GM, Suppressa P, Lastella P, Scarano V, Dani E, D’Aprile L, Triggiani V,and Sabbà C (Bari-Napoli).

15. Hereditary haemorrhagic telangiectasia: how to resolve the complex clinicalmanagement of a serious brain abscess. Suppressa P, Lenato GM, Lastella P, Gaetani M,Cavallo ML, Gaudio R, Burdi N, and Sabbà C (Bari-Taranto).

16. Eribulin in male patients with metastatic breast cancer: first report of clinical outcome.Mallamaci R, Giotta F, and Lavalle F (Bari).

17. Co-occurrence of MT-ND1 and MT-RNR1 mutations in a family with Leber's hereditaryoptic neuropathy and mental retardation. Bianco A, Galeandro V, Russo L, De Caro MF,Bisceglia L, D’Agruma L, Zoccolella S, Guerriero S, and Petruzzella V (Bari).

18. Fatal case of ecstasy-induced typical symptoms of neuroleptic malignant syndromeassociated with the DRD2/ANKK1-Taq1A polymorphism: a case report. Gabriele F,Balestra B, Capelli E, Locatelli CA, Petrolini VM, Pastoris O, and Coccini T (Pavia).

19. Pharmacokinetic and pharmacodynamic (PK/PD) evaluation to adapt therapy indifferent paediatric ages: the case of DEEP project. Del Vecchio GC, Ceci A, Bellanti F,Bonifazi D, Cosmi C, Filosa G, Lassandro G, Giordano P, Pitrolo L, Ruggieri L, Putti C, andDella Pasqua O (Bari-Pavia).

20. Pluripotent Stem Cells for Gene Therapy of Rare Diseases. Rubolino C, D’Aiuto L,Nimgaonka VL, Lasorsa FM, Barile SN, Imbrici P, Altamura C, Desaphy J-F, Palmieri L,Viggiano L (Pittsburgh-Bari)

Session 3 - Chair: Jean-François Desaphy

21. Migration and invasiveness of cells derived from human renal angiomyolipoma underdrugs and hormonal influence in vitro. Bertolini F, Casarotti, Colangelo D, and Mognetti B(Torino).

22. Ultrasonography of skeletal muscle in small animals: a new non invasive tool for pre-clinical studies in rare muscle diseases. Mele A, Rana F, Fonzino A , De Bellis M, Pierno S,Liantonio A, Desaphy JF, De Luca A, and Conte Camerino D (Bari).

23. Histological platform in pre-clinical studies in animal models of neuromusculardiseases. De Bellis M, Capogrosso RF, Mantuano P, Giustino A, Liantonio A, Pierno S, ConteCamerino D, and De Luca A (Bari).

24. Hereditary haemorrhagic telangiectasia and juvenile polyposis: two syndromes with ashared pathway. Lastella P, Suppressa P, Lenato GM, Dani E, D’Aprile L, Stella A Resta N,and Sabbà C (Bari).

25. Genetic and proteic evaluation of CLC1 channel expression in fast and slow ratskeletal muscles from birth to elderly: toward the development of new phenotype and agespecific therapies. Conte E, Musaraj K, Caloiero R, Fonzino A, Ventriglia G, Nicchia GP,Lograno MD, De Luca A, Pierno S, and Camerino GM (Bari).

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26. Contractile efficiency of dystrophic mdx mouse muscle: in vivo and ex vivoassessment of adaptation of functional end-points to exercise. Capogrosso RF,Mantuano P, Cozzoli A, Sanarica F, De Bellis M, Giustino A, Camerino GM, Grange RW, andDe Luca A (Bari).

27. Cell-Based screening for the identification of new biological markers for CentralNervous System autoimmune gliopathies. Palazzo C, Mastrapasqua M, Ruggieri M, NicchiaGP, Pisani F, Lavolpe V, Paolicelli D, Iaffaldano P, Luciannatelli E, Tortorella C, Trojano M,and Frigeri A (Bari).

28. Cardiolipin fingerprinting of leukocytes by MALDI-TOF/MS as a screening tool forBarth syndrome. Lobasso S, Angelini R, Gorgoglione R, Bowron A, Steward CG, and CorcelliA (Bari-Bristol).

29. Exome sequencing in Limbe Girdle Muscular Dystrophy type 1H (LGMD1H). BiancoA, Bisceglia L, Galeandro V, Santorelli MF, Castellana S, De Bonis P, Palumbo O, Mazza T,Nigro V, and Petruzzella V (Bari-Napoli).

30. The H-bond between L53 and T56 does not play a role for Aquaporin-4 epitopeformation in Neuromyelitis Optica. Pisani F, Simone L, Gargano CD, De Bellis M, Cibelli A,Mola MG, Frigeri A, Svelto M, and Nicchia GP (Bari-Foggia-Roma-New York).

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