Incarichi Societari
1995 - 2001 Segretario della "World Muscle Society" (WMS) - Società mondiale delle malattie NeuroMuscolari
Incarichi Editoriali
1991 - presente Associate Editor della rivista Neuromuscular Disorders
2010 - presente Editorial Board Member of Skeletal Muscle
Aree di interesse clinico
Malattie dei nervi, muscoli, e midollo spinale; neurologia in Ortopedia, riabilitazione in Ortopedia, fibromialgia.
Aree di interesse nella ricerca
Malattie neuromuscolari, patologia ortopedica, riabilitazione
Principali risultati della Ricerca e Collaborazioni Scientifiche
La mia ricerca clinica è stata rivolta inizialmente allo studio della storia naturale e alla riabilitazione delle più importanti malattie neuromuscolari: distrofia muscolare di Duchenne, atrofia muscolare spinale, e distrofie muscolari congenite. Ho promosso la riabilitazione con tutori sia nella distrofia muscolare di Duchenne [1, 2 ] che nella atrofia muscolare spinale [3 ]. In collaborazione con il centro scoliosi della Rizzoli ho maturato una vasta esperienza nel trattamento ortopedico e chirurgico della scoliosi nella distrofia muscolare di Duchenne [4 ]e atrofia muscolare spinale [5-7 ]. La valutazione della forza muscolare con metodiche quantitative nelle malattie neuromuscolari è stata poi fonte di studio e di pubblicazioni [8, 9 ]. Sono poi stato attivamente coinvolto nella grande ricerca europea dei geni responsabili di malattie neuromuscolari ereditarie. I miei contributi clinici sono stati fondamentali per la scoperta di 13 geni causa di malattie neuromuscolari ereditarie: distrofia muscolare dei cingoli 2D [10 ], distrofia muscolare autosomica dominante di Emery-Dreifuss [11 ]; autosomica recessiva EDMD [12 ], distrofia muscolare congenita di Walker-Warburg- POMT1 [13 ]; distrofia muscolare congenita -MDC1D [14 ]; displasia mandibulo-acrale [15 ]; distrofia muscolare congenita di Ullrich [16 ]; distrofia muscolare congenita con rachide rigido e sindrome respiratoria restrittiva RSMD1 [17 ]; neuropatia con cataratta congenita dismorfismi facciali e mioglobinuria (CCFDN)[18 ], sindrome di Silver [19 ], distrofia muscolare congenita Walker-Warburg - POMT2 [20 ], miopatia miosclerotica [21 ], e miopatia di Bethlem autosomico recessiva [22 ].
Sono stato il coordinatore scientifico del progetto finanziato dall'UE # QLG1-CT-1999-00870 e denominato “Myocluster” (2000-2003) [23 ]. Questo cluster ha coinvolto i principali centri di miologia europei con l'obiettivo di far progredire le conoscenze sugli aspetti clinici, patologici, biochimici e genetici delle distrofie muscolari congenite, della distrofia di Emery-Dreifuss e della miopatia di Bethlem e Ullrich. Ho coordinato diversi workshop internazionali organizzati dall'European NeuroMuscular Centre - ENMC [24-35 ].
Trial Clinici. Ho promosso il primo studio pilota del trattamento precoce con steroidi nei pazienti Duchenne distrofia muscolare [36-38 ]. Sono stato P.I. e coordinatore del progetto Telethon - Italian SMART (Spinal Muscular Atrophy Randomized clinical Trial) che ha coinvolto sette centri italiani e la più numerosa popolazione affetta da questa patologia [39 ].
Dal 2000 sono attivamente coinvolto nei progetti finanziati da Telethon sulle miopatie da deficit di collagene tipo VI. Tali studi, in collaborazione con i laboratori di biologia di Padova diretti da Paolo Bernardi e da Paolo Bonaldo, hanno permesso di individuare i meccanismi patogenetici di tali miopatie: disfunzione mitocondriale [40 ]e deficit autofagico [41 ]e la loro possibilità di correzione nel modello animale e in trial clinici pilota nei pazienti [42-44 ].
Ho collaborato alla stesura delle linee guida per monitorare l'autofagia [45 ]. Ho coordinato l’approfondimento di nuovi meccanismi patogenetici nelle malattie muscolari che sono stati raccolti in e-book [46, 47 ].
Pubblicazioni scientifiche
450 pubblicazioni scientifiche su riviste con impact factor, 11 capitoli di libri, 3 libri, 2 e-book.
H-index: 75 (Google Scholar)
https://scholar.google.it/citations?user=yeUvc9sAAAAJ&hl=it
Lista delle pubblicazioni citate nel CV
1. Granata C, Giannini S, Rubbini L, Corbascio M, Bonfiglioli S, Sabattini L, Merlini L: [Orthopedic surgery to prolong walking in Duchenne muscular dystrophy]. Chir Organi Mov 1988, 73(3):237-248.
2. Granata C, Giannini S, Ballestrazzi A, Merlini L: Early surgery in Duchenne muscular dystrophy. Experience at Istituto Ortopedico Rizzoli, Bologna, Italy [letter]. Neuromuscul Disord 1994,4(1):87-88.
3. Granata C, Cornelio F, Bonfiglioli S, Mattutini P, Merlini L: Promotion of ambulation of patients with spinal muscular atrophy by early fitting of knee-ankle-foot orthoses. Dev Med Child Neurol 1987, 29(2):221-224.
4. Granata C, Merlini L, Cervellati S, Ballestrazzi A, Giannini S, Corbascio M, Lari S: Long-term results of spine surgery in Duchenne muscular dystrophy [see comments]. Neuromuscul Disord 1996,6(1):61-68.
5. Granata C, Merlini L, Magni E, Marini ML, Stagni SB: Spinal muscular atrophy: natural history and orthopaedic treatment of scoliosis. Spine 1989, 14(7):760-762.
6. Granata C, Cervellati S, Ballestrazzi A, Corbascio M, Merlini L: Spine surgery in spinal muscular atrophy: long-term results. Neuromuscul Disord 1993, 3(3):207-215.
7. Merlini L, Granata C, Bonfiglioli S, Marini ML, Cervellati S, Savini R: Scoliosis in spinal muscular atrophy: natural history and management. Dev Med Child Neurol 1989, 31(4):501-508.
8. Merlini L, Dell'Accio D, Granata C: Reliability of dynamic strength knee muscle testing in children. J Orthop Sports Phys Ther 1995, 22(2):73-76.
9. Merlini L, Mazzone ES, Solari A, Morandi L: Reliability of hand-held dynamometry in spinal muscular atrophy. Muscle Nerve 2002, 26(1):64-70.
10. Piccolo F, Roberds SL, Jeanpierre M, Leturcq F, Azibi K, Beldjord C, Carrie A, Recan D, Chaouch M, Reghis Aet al: Primary adhalinopathy: a common cause of autosomal recessive muscular dystrophy of variable severity. Nat Genet 1995, 10(2):243-245.
11. Bonne G, Di Barletta MR, Varnous S, Becane HM, Hammouda EH, Merlini L, Muntoni F, Greenberg CR, Gary F, Urtizberea JAet al: Mutations in the gene encoding lamin A/C cause autosomal dominant Emery- Dreifuss muscular dystrophy. Nat Genet 1999, 21(3):285-288.
12. Raffaele Di Barletta M, Ricci E, Galluzzi G, Tonali P, Mora M, Morandi L, Romorini A, Voit T, Orstavik KH, Merlini Let al: Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy. Am J Hum Genet 2000, 66(4):1407-1412.
13. Beltran-Valero de Bernabe D, Currier S, Steinbrecher A, Celli J, van Beusekom E, van der Zwaag B, Kayserili H, Merlini L, Chitayat D, Dobyns WBet al: Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker-Warburg syndrome. Am J Hum Genet 2002, 71(5):1033-1043.
14. Longman C, Brockington M, Torelli S, Jimenez-Mallebrera C, Kennedy C, Khalil N, Feng L, Saran RK, Voit T, Merlini Let al: Mutations in the human LARGE gene cause MDC1D, a novel form of congenital muscular dystrophy with severe mental retardation and abnormal glycosylation of {alpha}-dystroglycan. Hum Mol Genet 2003.
15. Novelli G, Muchir A, Sangiuolo F, Helbling-Leclerc A, D'Apice MR, Massart C, Capon F, Sbraccia P, Federici M, Lauro Ret al: Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. Am J Hum Genet 2002, 71(2):426-431.
16. Demir E, Sabatelli P, Allamand V, Ferreiro A, Moghadaszadeh B, Makrelouf M, Topaloglu H, Echenne B, Merlini L, Guicheney P: Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy. Am J Hum Genet 2002, 70(6):1446-1458.
17. Moghadaszadeh B, Petit N, Jaillard C, Brockington M, Roy SQ, Merlini L, Romero N, Estournet B, Desguerre I, Chaigne Det al: Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome. Nat Genet 2001, 29(1):17-18.
18. Varon R, Gooding R, Steglich C, Marns L, Tang H, Angelicheva D, Yong KK, Ambrugger P, Reinhold A, Morar Bet al: Partial deficiency of the C-terminal-domain phosphatase of RNA polymerase II is associated with congenital cataracts facial dysmorphism neuropathy syndrome. Nat Genet 2003,35(2):185-189.
19. Windpassinger C, Auer-Grumbach M, Irobi J, Patel H, Petek E, Horl G, Malli R, Reed JA, Dierick I, Verpoorten Net al: Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome. Nat Genet 2004, 36(3):271-276.
20. van Reeuwijk J, Janssen M, van den Elzen C, Beltran-Valero de Bernabe D, Sabatelli P, Merlini L, Boon M, Scheffer H, Brockington M, Muntoni Fet al: POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome. J Med Genet 2005, 42(12):907-912.
21. Merlini L, Martoni E, Grumati P, Sabatelli P, Squarzoni S, Urciuolo A, Ferlini A, Gualandi F, Bonaldo P: Autosomal recessive myosclerosis myopathy is a collagen VI disorder. Neurology 2008,71(16):1245-1253.
22. Gualandi F, Urciuolo A, Martoni E, Sabatelli P, Squarzoni S, Bovolenta M, Messina S, Mercuri E, Franchella A, Ferlini Aet al: Autosomal recessive Bethlem myopathy.Neurology 2009, 73(1):1883-1891.
23. Merlini L: Myo-Cluster. Neuromusc Disord2001, 11(1):101-102.
24. Allamand V, Merlini L, Bushby K: 166th ENMC International Workshop on Collagen type VI-related Myopathies, 22-24 May 2009, Naarden, The Netherlands.Neuromuscul Disord 2010, 20(5):346-354.
25. Bonne G, Capeau J, De Visser M, Duboc D, Merlini L, Morris GE, Muntoni F, Recan D, Sewry C, Squarzoni Set al: 82nd ENMC international workshop, 5th international Emery-Dreifuss muscular dystrophy (EDMD) workshop, 1st Workshop of the MYO-CLUSTER project EUROMEN (European muscle envelope nucleopathies), 15-16 September 2000, Naarden, The Netherlands. Neuromuscul Disord 2002, 12(2):187-194.
26. Bonne G, Dubowitz V, Ellis J, Hausmanova-Petrusewicz I, Merlini L, Morris G, Muntoni F, Recan-Budiartha D, Sewry C, Toniolo Det al: 60th ENMC International Workshop: non X-linked Emery-Dreifuss Muscular Dystrophy 5-7 June 1998, Naarden, The Netherlands. Neuromuscul Disord 1999,9(2):115-121.
27. Bonne G, Yaou RB, Beroud C, Boriani G, Brown S, de Visser M, Duboc D, Ellis J, Hausmanowa-Petrusewicz I, Lattanzi Get al: 108th ENMC International Workshop, 3rd Workshop of the MYO-CLUSTER project: EUROMEN, 7th International Emery-Dreifuss Muscular Dystrophy (EDMD) Workshop, 13-15 September 2002, Naarden, The Netherlands. Neuromuscul Disord 2003, 13(6):508-515.
28. Kalaydjieva L, Lochmuller H, Tournev I, Baas F, Beres J, Colomer J, Guergueltcheva V, Herrmann R, Karcagi V, King Ret al: 125th ENMC International Workshop: Neuromuscular disorders in the Roma (Gypsy) population, 23-25 April 2004, Naarden, The Netherlands. Neuromuscul Disord 2005, 15(1):65-71.
29. Merlini L, Estournet-Mathiaud B, Iannaccone S, Melki J, Muntoni F, Rudnik-Schoneborn S, Topaloglu H, Vita G, Voit T: 90th ENMC international workshop: European Spinal Muscular Atrophy Randomised Trial (EuroSMART) 9-10 February 2001, Naarden, The Netherlands. Neuromuscul Disord 2002, 12(2):201-210.
30. Merlini L, Nishino I, Consortium for Autophagy in Muscular D: 201st ENMC International Workshop: Autophagy in muscular dystrophies--translational approach, 1-3 November 2013, Bussum, The Netherlands. Neuromuscul Disord 2014, 24(6):546-561.
31. Muntoni F, Bertini E, Bonnemann C, Brockington M, Brown S, Bushby K, Fiszman M, Korner C, Mercuri E, Merlini Let al: 98th ENMC International Workshop on Congenital Muscular Dystrophy (CMD), 7th Workshop of the International Consortium on CMD, 2nd Workshop of the MYO CLUSTER project GENRE. 26-28th October, 2001, Naarden, The Netherlands.Neuromuscul Disord 2002, 12(9):889-896.
32. Muntoni F, Blake D, Brockington M, Brown S, Hayashi YK, Merlini L, Sabatelli P, Topaloglu H, Voit T, Guicheney P: 85th ENMC International Workshop on Congenital Muscular Dystrophy. 6th International CMD Workshop. 1st Workshop of the Myo-Cluster Project 'GENRE'. 27-28th October 2000, Naarden, The Netherlands.Neuromuscul Disord 2002, 12(1):69-78.
33. Muntoni F, Valero de Bernabe B, Bittner R, Blake D, van Bokhoven H, Brockington M, Brown S, Bushby K, Campbell KP, Fiszman Met al: 114th ENMC International Workshop on Congenital Muscular Dystrophy (CMD) 17-19 January 2003, Naarden, The Netherlands: (8th Workshop of the International Consortium on CMD; 3rd Workshop of the MYO-CLUSTER project GENRE).Neuromuscul Disord 2003, 13(7-8):579-588.
34. Pepe G, Bertini E, Bonaldo P, Bushby K, Giusti B, de Visser M, Guicheney P, Lattanzi G, Merlini L, Muntoni Fet al: Bethlem myopathy (BETHLEM) and Ullrich scleroatonic muscular dystrophy: 100th ENMC international workshop, 23-24 November 2001, Naarden, The Netherlands. Neuromuscul Disord 2002,12(10):984-993.
35. Pepe G, de Visser M, Bertini E, Bushby K, Vanegas OC, Chu ML, Lattanzi G, Merlini L, Muntoni F, Urtizberea A: Bethlem myopathy (BETHLEM) 86th ENMC international workshop, 10-11 November 2000, Naarden, The Netherlands. Neuromuscul Disord 2002, 12(3):296-305.
36. Merlini L: A 19-year-old ambulant Duchenne patient with stunted growth on long-term corticosteroids. Neuromuscul Disord 2014, 24(5):417-418.
37. Merlini L, Cicognani A, Malaspina E, Gennari M, Gnudi S, Talim B, Franzoni E: Early prednisone treatment in Duchenne muscular dystrophy. Muscle Nerve 2003, 27(2):222-227.
38. Merlini L, Gennari M, Malaspina E, Cecconi I, Armaroli A, Gnudi S, Talim B, Ferlini A, Cicognani A, Franzoni E: Early corticosteroid treatment in 4 Duchenne muscular dystrophy patients: 14-year follow-up. Muscle Nerve 2012, 45(6):796-802.
39. Merlini L, Solari A, Vita G, Bertini E, Minetti C, Mongini T, Mazzoni E, Angelini C, Morandi L: Role of gabapentin in spinal muscular atrophy: results of a multicenter, randomized Italian study. J Child Neurol 2003, 18(8):537-541.
40. Irwin WA, Bergamin N, Sabatelli P, Reggiani C, Megighian A, Merlini L, Braghetta P, Columbaro M, Volpin D, Bressan GMet al: Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency. Nat Genet 2003, 35(4):367-371.
41. Grumati P, Coletto L, Sabatelli P, Cescon M, Angelin A, Bertaggia E, Blaauw B, Urciuolo A, Tiepolo T, Merlini Let al: Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration. Nat Med 2010.
42. Merlini L, Angelin A, Tiepolo T, Braghetta P, Sabatelli P, Zamparelli A, Ferlini A, Maraldi NM, Bonaldo P, Bernardi P: Cyclosporin A corrects mitochondrial dysfunction and muscle apoptosis in patients with collagen VI myopathies. Proc Natl Acad Sci U S A 2008,105(13):5225-5229.
43. Merlini L, Sabatelli P, Armaroli A, Gnudi S, Angelin A, Grumati P, Michelini ME, Franchella A, Gualandi F, Bertini Eet al: Cyclosporine A in Ullrich congenital muscular dystrophy: long-term results. Oxidative medicine and cellular longevity 2011, 2011:139194.
44. Castagnaro S, Pellegrini C, Pellegrini M, Chrisam M, Sabatelli P, Toni S, Grumati P, Ripamonti C, Pratelli L, Maraldi NMet al: Autophagy activation in COL6 myopathic patients by a low-protein-diet pilot trial. Autophagy 2016:1-12.
45. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli Ket al: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 2016,12(1):1-222.
46. Merlini L, Faldini C, Bonaldo P: Editorial: Muscle-Tendon-Innervation Unit: Degeneration and Aging-Pathophysiological and Regeneration Mechanisms. Frontiers in aging neuroscience 2016, 8:320.
47. Merlini L, Bonaldo P, Marzetti E: Editorial: Pathophysiological Mechanisms of Sarcopenia in Aging and in Muscular Dystrophy: A Translational Approach. Frontiers in aging neuroscience 2015, 7:153.
