Dott. Umberto Manera

NEUROSCIENZE
Phd: 34th cycle
Matriculation number: 303693

Contacts

Supervisor

Research activities

Determinants of motor and cognitive phenotypes of ALS

Abstract:
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which motor neuron degeneration usually starts with a focal clinical onset subsequently expanding to different body regions and frontotemporal cognitive decline is often associated to motor symptoms. Many different genetic and environmental factors are associated with an increased risk of developing ALS and some of them seem to be specifically linked to clinical aspects such as age of onset, survival or dementia.
This project aims to investigate the relationship among genetics, environment and ALS motor and cognitive phenotypes by analyzing: a) the synergistic role of ALS-related genes mutations and of environmental risk factors in determining clinical features and specific phenotypes b) the identification of different motor and cognitive “spreading phenotypes” c) the instrumental assessment and predictability of “spreading phenotypes” using biomarkers at diagnosis d) the tracing back of a longitudinal spreading patterns to its environmental and genetic determinants.

1: Calvo A, Chiò A, Pagani M, Cammarosano S, Dematteis F, Moglia C, Solero L, Manera U, Martone T, Brunetti M, Balma M, Castellano G, Barberis M, Cistaro A, Artusi CA, Vasta R, Montanaro E, Romagnolo A, Iazzolino B, Canosa A, Carrara G, Valentini C, Li TQ, Nobili F, Lopiano L, Rizzone MG. Parkinsonian traits in amyotrophic lateral sclerosis (ALS): a prospective population-based study. J Neurol. 2019 Apr 4. doi: 10.1007/s00415-019-09305-0. [Epub ahead of print] PubMed PMID: 30949819.

2: Visser AE, D'Ovidio F, Peters S, Vermeulen RC, Beghi E, Chiò A, Veldink JH, Logroscino G, Hardiman O, van den Berg LH; Euro-MOTOR consortium. Multicentre, population-based, case-control study of particulates, combustion products and amyotrophic lateral sclerosis risk. J Neurol Neurosurg Psychiatry. 2019 Mar 8. pii: jnnp-2018-319779. doi: 10.1136/jnnp-2018-319779. [Epub ahead of print] PubMed PMID: 30850472.

3: Iazzolino B, Pain D, Peotta L, Calvo A, Moglia C, Canosa A, Manera U, Ilardi A, Bombaci A, Zucchetti JP, Mora G, Chio A. Validation of the revised classification of cognitive and behavioural impairment in ALS. J Neurol Neurosurg Psychiatry. 2019 Feb 7. pii: jnnp-2018-319696. doi: 10.1136/jnnp-2018-319696. [Epub ahead of print] PubMed PMID: 30733331.

4: Bandres-Ciga S, Noyce AJ, Hemani G, Nicolas A, Calvo A, Mora G; ITALSGEN Consortium; International ALS Genomics Consortium, Tienari PJ, Stone DJ, Nalls MA, Singleton AB, Chiò A, Traynor BJ. Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis. Ann Neurol. 2019 Apr;85(4):470-481. doi: 10.1002/ana.25431. Epub 2019 Mar 13. PubMed PMID: 30723964; PubMed Central PMCID: PMC6450729.

5: Moglia C, Calvo A, Grassano M, Canosa A, Manera U, D'Ovidio F, Bombaci A, Bersano E, Mazzini L, Mora G, Chiò A; Piemonte and Valle d’Aosta Register for ALS (PARALS). Early weight loss in amyotrophic lateral sclerosis: outcome relevance and clinical correlates in a population-based cohort. J Neurol Neurosurg Psychiatry. 2019 Jun;90(6):666-673. doi: 10.1136/jnnp-2018-319611. Epub 2019 Jan 10. PubMed PMID: 30630957.

6: D'Ovidio F, Rooney JPK, Visser AE, Manera U, Beghi E, Logroscino G, Vermeulen RCH, Veldink JH, van den Berg LH, Hardiman O, Chiò A; Euro-MOTOR consortium. Association between alcohol exposure and the risk of amyotrophic lateral sclerosis in the Euro-MOTOR study. J Neurol Neurosurg Psychiatry. 2019 Jan;90(1):11-19. doi: 10.1136/jnnp-2018-318559. Epub 2018 Aug 3. PubMed PMID: 30076269.

7: Chiò A, Mazzini L, D'Alfonso S, Corrado L, Canosa A, Moglia C, Manera U, Bersano E, Brunetti M, Barberis M, Veldink JH, van den Berg LH, Pearce N, Sproviero W, McLaughlin R, Vajda A, Hardiman O, Rooney J, Mora G, Calvo A, Al-Chalabi A. The multistep hypothesis of ALS revisited: The role of genetic mutations. Neurology. 2018 Aug 14;91(7):e635-e642. doi: 10.1212/WNL.0000000000005996. Epub 2018 Jul 25. PubMed PMID: 30045958; PubMed Central PMCID: PMC6105040.

8: Visser AE, Rooney JPK, D'Ovidio F, Westeneng HJ, Vermeulen RCH, Beghi E, Chiò A, Logroscino G, Hardiman O, Veldink JH, van den Berg LH; Euro-MOTOR consortium. Multicentre, cross-cultural, population-based, case-control study of physical activity as risk factor for amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2018 Aug;89(8):797-803. doi: 10.1136/jnnp-2017-317724. Epub 2018 Apr 23. PubMed PMID: 29685899.

9: Nicolas A, Kenna KP, Renton AE, (…) ITALSGEN Consortium, (…), Chiò A, Shaw CE, Traynor BJ, Landers JE. Genome-wide Analyses Identify KIF5A as a Novel ALS Gene. Neuron. 2018 Mar 21;97(6):1268-1283.e6. doi: 10.1016/j.neuron.2018.02.027. PubMed PMID: 29566793; PubMed Central PMCID: PMC5867896.

10: Chiò A, Mora G, Moglia C, Manera U, Canosa A, Cammarosano S, Ilardi A, Bertuzzo D, Bersano E, Cugnasco P, Grassano M, Pisano F, Mazzini L, Calvo A; Piemonte and Valle d’Aosta Register for ALS (PARALS). Secular Trends of Amyotrophic Lateral Sclerosis: The Piemonte and Valle d'Aosta Register. JAMA Neurol. 2017 Sep 1;74(9):1097-1104. doi: 10.1001/jamaneurol.2017.1387. PubMed PMID: 28692730; PubMed Central PMCID: PMC5710181.

11: Moglia C, Calvo A, Canosa A, Bertuzzo D, Cugnasco P, Solero L, Grassano M, Bersano E, Cammarosano S, Manera U; Parals, Pisano F, Mazzini L, Dalla Vecchia LA, Mora G, Chiò A. Influence of arterial hypertension, type 2 diabetes and cardiovascular risk factors on ALS outcome: a population-based study. Amyotroph Lateral Scler Frontotemporal Degener. 2017 Nov;18(7-8):590-597. doi: 10.1080/21678421.2017.1336560. Epub 2017 Jun 15. PubMed PMID: 28616937.

12: Calvo A, Canosa A, Bertuzzo D, Cugnasco P, Solero L, Clerico M, De Mercanti S, Bersano E, Cammarosano S, Ilardi A, Manera U, Moglia C, Marinou K, Bottacchi E, Pisano F, Mora G, Mazzini L, Chiò A. Influence of cigarette smoking on ALS outcome: a population-based study. J Neurol Neurosurg Psychiatry. 2016 Nov;87(11):1229-1233. doi: 10.1136/jnnp-2016-313793. Epub 2016 Sep 21. PubMed PMID: 27656044.

13: Bartolo M, Chiò A, Ferrari S, Tassorelli C, Tamburin S, Avenali M, Azicnuda E, Calvo A, Caraceni AT, Defazio G, DE Icco R, Formisano R, Franzoni S, Greco E, Jedrychowska I, Magrinelli F, Manera U, Marchioni E, Mariotto S, Monaco S, PaceA, Saviola D, Springhetti I, Tinazzi M, DE Tanti A; Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN). Assessing and treating pain in movement disorders, amyotrophic lateral sclerosis, severe acquired brain injury, disorders of consciousness, dementia, oncology and neuroinfectivology. Evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation. Eur J Phys Rehabil Med. 2016 Dec;52(6):841-854. Epub 2016 Aug 31. PubMed PMID: 27579582.

14: Sandrini G, Tamburin S, Paolucci S, Boldrini P, Saraceni VM, Smania N; Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN). Time for a Consensus Conference on pain in neurorehabilitation. Eur J Phys Rehabil Med. 2016 Oct;52(5):714-716. Epub 2016 Jul 12. PubMed PMID: 27406655.

15: Borghero G, Pugliatti M, Marrosu F, Marrosu MG, Murru MR, Floris G, Cannas A, Occhineri P, Cau TB, Loi D, Ticca A, Traccis S, Manera U, Canosa A, Moglia C, Calvo A, Barberis M, Brunetti M, Gibbs JR, Renton AE, Errichiello E, Zoledziewska M, Mulas A, Qian Y, Din J, Pliner HA, Traynor BJ, Chiò A; ITALSGEN and SARDINALS Consortia. TBK1 is associated with ALS and ALS-FTD in Sardinian patients. Neurobiol Aging. 2016 Jul;43:180.e1-5. doi: 10.1016/j.neurobiolaging.2016.03.028. Epub 2016 Apr 9. PubMed PMID: 27156075.

16: Chiò A, Mora G, Sabatelli M, Caponnetto C, Lunetta C, Traynor BJ, Johnson JO, Nalls MA, Calvo A, Moglia C, Borghero G, Trojsi F, La Bella V, Volanti P, Simone I, Salvi F, Logullo FO, Riva N, Carrera P, Giannini F, Mandrioli J, Tanel R, Capasso M, Tremolizzo L, Battistini S, Murru MR, Origone P, Zollino M, Penco S; ITALSGEN consortium; SARDINIALS consortium, Mazzini L, D'Alfonso S, Restagno G, Brunetti M, Barberis M, Conforti FL. ATNX2 is not a regulatory gene in Italian amyotrophic lateral sclerosis patients with C9ORF72 GGGGCC expansion. Neurobiol Aging. 2016 Mar;39:218.e5-8. doi: 10.1016/j.neurobiolaging.2015.11.027. Epub 2015 Dec 8. PubMed PMID: 26733254; PubMed Central PMCID: PMC4775342.

17: Benedetti MD, Pugliatti M, D'Alessandro R, Beghi E, Chiò A, Logroscino G, Filippini G, Galeotti F, Massari M, Santuccio C, Raschetti R; ITANG Study Group. A Multicentric Prospective Incidence Study of Guillain-Barré Syndrome in Italy. The ITANG Study. Neuroepidemiology. 2015;45(2):90-9. doi: 10.1159/000438752. Epub 2015 Aug 29. PubMed PMID: 26329724.

18: Borghero G, Pugliatti M, Marrosu F, Marrosu MG, Murru MR, Floris G, Cannas A, Parish LD, Cau TB, Loi D, Ticca A, Traccis S, Manera U, Canosa A, Moglia C, Calvo A, Barberis M, Brunetti M, Renton AE, Nalls MA, Traynor BJ, Restagno G, Chiò A; ITALSGEN and SARDINALS consortia. ATXN2 is a modifier of phenotype in ALS patients of Sardinian ancestry. Neurobiol Aging. 2015 Oct;36(10):2906.e1-5. doi: 10.1016/ j.neurobiolaging.2015.06.013. Epub 2015 Jun 25. PubMed PMID: 26208502; PubMed Central PMCID: PMC5193218.

19: Canosa A, Calvo A, Moglia C, Barberis M, Brunetti M, Cammarosano S, Manera U, Ilardi A, Restagno G, Chiò A. A novel p.E121G heterozygous missense mutation of SOD1 in an apparently sporadic ALS case with a 14-year course. Amyotroph Lateral Scler Frontotemporal Degener. 2015 Mar;16(1-2):127-8. doi: 10.3109/21678421.2014.966312. Epub 2014 Oct 9. PubMed PMID: 25299943.

20: Borghero G, Pugliatti M, Marrosu F, Marrosu MG, Murru MR, Floris G, Cannas A, Parish LD, Occhineri P, Cau TB, Loi D, Ticca A, Traccis S, Manera U, Canosa A, Moglia C, Calvo A, Barberis M, Brunetti M, Pliner HA, Renton AE, Nalls MA, Traynor BJ, Restagno G, Chiò A; ITALSGEN and SARDINALS Consortia. Genetic architecture of ALS in Sardinia. Neurobiol Aging. 2014 Dec;35(12):2882.e7-2882.e12. doi: 10.1016/j.neurobiolaging.2014.07.012. Epub 2014 Jul 18. PubMed PMID: 25123918; PubMed Central PMCID: PMC4252367.

Poster prize selection “The spreading of symptoms at diagnosis in ALS is a marker of prognosis: a population-based study” - 27th International Symposium on ALS/MND, Dublin 2016