Email luciano.merlini@unibo.it [mailto:luciano.merlini@unibo.it]
luciano.merlini@unife.it [mailto:luciano.merlini@unife.it]
Education and training
Medical degree cum laude at the University of Bologna (1962-1968)
Specialist in Neurology, University of Bologna (1972)
Specialist in Physical Therapy, University of Bologna (1975)
Positions
1974 - 2005 Chief of the Neuromuscular Unit of the Istituto Ortopedico Rizzoli, Bologna, Italy
2005 - 2012 Consultant: Neuromuscular Laboratory, Dept. of Medical Genetics, University of Ferrara
1995 - 2001 Secretary of World Muscle Society - WMS
1991 - present Associate Editor of Neuromuscular Disorders
2010 – present Editorial Board Member of Skeletal Muscle
Publications
More than 450 articles in peer review journals
H-index = 75
https://scholar.google.it/citations?user=yeUvc9sAAAAJ&hl=en
Research activity
In the first phase of my clinical research I have been interested in the study of the natural history and rehabilitation of the most relevant neuromuscular disorders: Duchenne muscular dystrophy, spinal muscular atrophy, and congenital muscular dystrophies. I have promoted rehabilitation with callipers both in Duchenne muscular dystrophy [1, 2] and in spinal muscular atrophy [3]. In collaboration with the scoliosis centre of the Rizzoli I have gained extensive experience in the orthopaedic and surgical treatment of scoliosis in Duchenne muscular dystrophy [4] and spinal muscular atrophy [5-7]. Muscle strength testing in neuromuscular disorders has been also the source of interest and publications [8, 9]. Subsequently I have actively been involved in the great European search of the genes responsible of hereditary neuromuscular disorders. My clinical research efforts have been instrumental in the discovery of several gene-causing disorders: Limb girdle muscular dystrophy 2D [10], autosomal dominant Emery-Dreifuss muscular dystrophy [11]; autosomal recessive EDMD [12], POMT1 Walker-Warburg congenital muscular dystrophy [13]; congenital muscular dystrophy MDC1D [14]; mandibulo-acral dysplasia [15]; Ullrich congenital muscular dystrophy [16]; congenital muscular dystrophy with spine rigidity and restrictive respiratory syndrome RSMD1 [17]; Marinesco-Sjogren/myoglobinuria/CCFDN congenital cataract facial dysmorphism neuropathy [18], Silver syndrome [19], POMT2 - Walker-Warburg congenital muscular dystrophy [20], Myosclerosis Myopathy [21], Familial isolated hyperCKaemia CAV-3 [22], Autosomal dominant spastic paraplegia 30-SPG30 [23].
I have been the scientific coordinator of the EU funded project “Myocluster” (2000-2003). This was a cluster of European myology research groups with the aim to advance knowledge on the clinical, pathological, biochemical, and genetic aspects of congenital muscular dystrophies (GENRE; project leader Francesco MUNTONI), Emery-Dreifuss muscular dystrophies (EUROMEN; project leader Ketty SCHWARTZ) and Bethlem myopathy (BETHLEM; project leader Guglielmina PEPE).
More recently I have been involved in the organization of clinical trials in neuromuscular disorders. I have promoted the first pilot study of early treatment with steroids in Duchenne muscular dystrophy patients [24, 25]. I have received a Telethon grant for the first multicentre trial in spinal muscular atrophy, called Italian SMART (Spinal Muscular Atrophy Randomised clinical Trial). The results of this trial, which involved seven Italian centres and the largest population of this disorder ever studied has been recently published [26]. In addition I have coordinated an ENMC funded workshop with the aim to promote European clinical trials in spinal muscular atrophy (90th ENMC international workshop: European Spinal Muscular Atrophy Randomised Trial (EuroSMART) 9-10 February 2001, Naarden, The Netherlands) [27]. I am involved in the Telethon funded project on Col6-related myopathies. We found a latent dysfunction dysfunctional mitochondria and spontaneous apoptosis, leading to myofiber degeneration in these disorders and proved its correction with CsA [28]. I organized a pilot trial with CsA in patients with Col6-related myopathies [29, 30]. We have now demonstrate that this persistence of abnormal organelles and apoptosis are caused by defective autophagy [31]. I performed a trial to modulate autophagy with “Low Protein Diet in Patients With Collagen VI Related Myopathies (LPD)” [32].
http://clinicaltrials.gov/ct2/show/NCT01438788 .
List of the publications referred in the text References
1. Granata C, Giannini S, Rubbini L, Corbascio M, Bonfiglioli S, Sabattini L, et al. [Orthopedic surgery to prolong walking in Duchenne muscular dystrophy]. Chir Organi Mov. 1988;73 3:237-48.
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 1:87-8.
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 2:221-4; doi: 10.1111/j.1469-8749.1987.tb02139.x.
4. Granata C, Merlini L, Cervellati S, Ballestrazzi A, Giannini S, Corbascio M, et al. Long-term results of spine surgery in Duchenne muscular dystrophy [see comments]. Neuromuscul Disord. 1996;6 1:61-8.
5. Granata C, Merlini L, Magni E, Marini ML, Stagni SB. Spinal muscular atrophy: natural history and orthopaedic treatment of scoliosis. Spine. 1989;14 7:760-2.
6. Granata C, Cervellati S, Ballestrazzi A, Corbascio M, Merlini L. Spine surgery in spinal muscular atrophy: long-term results. Neuromuscul Disord. 1993;3 3:207-15; doi: 10.1016/0960-8966(93)90061-n.
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 4:501-8; doi: 10.1111/j.1469-8749.1989.tb04029.x.
8. Merlini L, Dell'Accio D, Granata C. Reliability of dynamic strength knee muscle testing in children. J Orthop Sports Phys Ther. 1995;22 2:73-6; doi: 10.2519/jospt.1995.22.2.73.
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 S, Jeanpierre M, Leturcq F, Azibi K, Beldjord C, et al. Primary adhalinopathy: a common cause of autosomal recessive muscular dystrophy of variable severity. Nature Genetics. 1995;10:243-5.
11. Bonne G, Di Barletta MR, Varnous S, Becane HM, Hammouda EH, Merlini L, et al. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery- Dreifuss muscular dystrophy. Nat Genet. 1999;21 3:285-8.
12. Raffaele Di Barletta M, Ricci E, Galluzzi G, Tonali P, Mora M, Morandi L, et al. Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy. Am J Hum Genet. 2000;66 4:1407-12; doi: 10.1086/302869.
13. Beltran-Valero de Bernabe D, Currier S, Steinbrecher A, Celli J, van Beusekom E, van der Zwaag B, et 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 5:1033-43; doi: 10.1086/342975.
14. Longman C, Brockington M, Torelli S, Jimenez-Mallebrera C, Kennedy C, Khalil N, et 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, et al. Mandibuloacral dysplasia is caused by a mutation in LMNA-encoding lamin A/C. Am J Hum Genet. 2002;71 2:426-31; doi: 10.1086/341908.
16. Demir E, Sabatelli P, Allamand V, Ferreiro A, Moghadaszadeh B, Makrelouf M, et al. Mutations in COL6A3 cause severe and mild phenotypes of Ullrich congenital muscular dystrophy. Am J Hum Genet. 2002;70 6:1446-58.
17. Moghadaszadeh B, Petit N, Jaillard C, Brockington M, Roy SQ, Merlini L, et al. Mutations in SEPN1 cause congenital muscular dystrophy with spinal rigidity and restrictive respiratory syndrome. Nat Genet. 2001;29 1:17-8.
18. Varon R, Gooding R, Steglich C, Marns L, Tang H, Angelicheva D, et 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 2:185-9; doi: 10.1038/ng1243.
19. Windpassinger C A-GM, Irobi J, Patel H, Petek E, Horl G, Malli R, Reed JA, Dierick I, Verpoorten N, Warner TT, Proukakis C, Den Bergh PV, Verellen C, Maldergem LV, Merlini L, Jonghe PD, Timmerman V, Crosby AH, Wagner K. Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome. Nat Genet. 2004;36 3:271-6.
20. van Reeuwijk J, Janssen M, van den Elzen C, Beltran-Valero de Bernabe D, Sabatelli P, Merlini L, et al. POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker Warburg syndrome. J Med Genet. 2005.
21. Merlini L, Martoni E, Grumati P, Sabatelli P, Squarzoni S, Urciuolo A, et al. Autosomal recessive myosclerosis myopathy is a collagen VI disorder. Neurology. 2008;71 16:1245-53; doi: 10.1212/01.wnl.0000327611.01687.5e.
22. Merlini L, Carbone I, Capanni C, Sabatelli P, Tortorelli S, Sotgia F, et al. Familial isolated hyperCKaemia associated with a new mutation in the caveolin-3 (CAV-3) gene. J Neurol Neurosurg Psychiatry. 2002;73 1:65-7; doi: 10.1136/jnnp.73.1.65.
23. Salim R, Dahlqvist JR, Khawajazada T, Kass K, Revsbech KL, de Stricker Borch J, et al. Characteristic muscle signatures assessed by quantitative MRI in patients with Bethlem myopathy. Journal of neurology. 2020;267 8:2432-42; doi: 10.1007/s00415-020-09860-x.
24. Merlini L, Cicognani A, Malaspina E, Gennari M, Gnudi S, Talim B, et al. Early prednisone treatment in Duchenne muscular dystrophy. Muscle Nerve. 2003;27 2:222-7; doi: 10.1002/mus.10319.
25. Merlini L, Gennari M, Malaspina E, Cecconi I, Armaroli A, Gnudi S, et al. Early corticosteroid treatment in 4 Duchenne muscular dystrophy patients: 14-year follow-up. Muscle Nerve. 2012;45 6:796-802; doi: 10.1002/mus.23272.
26. Merlini L, Solari A, Vita G, Bertini E, Minetti C, Mongini T, et al. Role of gabapentin in spinal muscular atrophy: results of a multicenter, randomized Italian study. J Child Neurol. 2003;18 8:537-41; doi: 10.1177/08830738030180080501.
27. Merlini L, Estournet-Mathiaud B, Iannaccone S, Melki J, Muntoni F, Rudnik-Schoneborn S, et al. 90th ENMC international workshop: European Spinal Muscular Atrophy Randomised Trial (EuroSMART) 9-10 February 2001, Naarden, The Netherlands. Neuromuscul Disord. 2002;12 2:201-10; doi: 10.1016/s0960-8966(01)00272-3.
28. Irwin WA, Bergamin N, Sabatelli P, Reggiani C, Megighian A, Merlini L, et al. Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency. Nature genetics. 2003;35 4:367-71; doi: 10.1038/ng1270.
29. Merlini L, Angelin A, Tiepolo T, Braghetta P, Sabatelli P, Zamparelli A, et al. Cyclosporin A corrects mitochondrial dysfunction and muscle apoptosis in patients with collagen VI myopathies. Proc Natl Acad Sci U S A. 2008;105 13:5225-9.
30. Merlini L, Sabatelli P, Armaroli A, Gnudi S, Angelin A, Grumati P, et al. Cyclosporine A in Ullrich congenital muscular dystrophy: long-term results. Oxidative medicine and cellular longevity. 2011;2011:139194; doi: 10.1155/2011/139194.
31. Grumati P, Coletto L, Sabatelli P, Cescon M, Angelin A, Bertaggia E, et al. Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration. Nature medicine. 2010;16 11:1313-20; doi: 10.1038/nm.2247.
32. Castagnaro S, Pellegrini C, Pellegrini M, Chrisam M, Sabatelli P, Toni S, et al. Autophagy activation in COL6 myopathic patients by a low-protein-diet pilot trial. Autophagy. 2016:1-12; doi: 10.1080/15548627.2016.1231279.
