Official Title: “Family Studies in Neuromuscular Disorders”
The investigators laboratory has been studying families with a history of ALS for more than 25 years and is continuing to use new ways to understand how genes may play a role in ALS, motor neuron disease and other neuromuscular disorders.
The purpose of this study is to identify additional genes that may cause or put a person at risk for either familial ALS (meaning 2 or more people in a family who have had ALS), sporadic ALS, or other forms of motor neuron disease in the hopes of improving diagnosis and treatment. As new genes are found that may be linked to ALS in families or individuals, the investigators can then further study how that gene may be contributing to the disease by studying it down to the protein and molecular level. This includes all forms of ALS, motor neuron disease and ALS with fronto-temporal dementia(ALS/FTD).
Thus far, one gene has been identified that is responsible for about 20% of all cases of familial ALS (FALS). That gene is the SOD1 (superoxide dismutase) gene. Another 12 or more other genes have now been identified that are responsible for another 40-50% of familial cases. However, for about 30% of families with FALS, the gene(s) are still unknown.
The investigators also will continue to work with families already identified to carry one of the known genes associated with ALS, such as SOD1, FUS/TLS, TDP-43, C9orf72 and others as the investigators study these genes further.
- Study Type: Observational
- Study Design: Time Perspective: Prospective
- Study Primary Completion Date: October 2018
Detailed Clinical Trial Description
Participants will be asked to provide a blood sample and to complete a couple of questionnaires regarding their overall medical health and some environmental risk factors. Medical records will be requested for all those diagnosed with one of the study diseases to allow the researchers to review details of their clinical disease symptoms, neurological exams and test results.
Participants do not need to travel to Massachusetts for this study. Samples can be obtained locally at no costs to the participant. Family members may be included in the study depending on family history and their relationship to the affected individual.
Arms, Groups and Cohorts in this Clinical Trial
- Familial and Sporadic ALS
- Individuals with ALS and families with a history of two or more people in the family who have had ALS or other forms of motor neuron disease.
Outcome Measures for this Clinical Trial
- identification of new genes that may contribute to ALS
- Time Frame: 2018
Safety Issue?: No
- Time Frame: 2018
Criteria for Participation in this Clinical Trial
- diagnosis of or family history of ALS,MND,ALS with dementia, or PLS.
- willingness to provide a blood sample for study use
- unwilling to provide a blood or saliva sample
Gender Eligibility for this Clinical Trial: Both
Minimum Age for this Clinical Trial: N/A
Maximum Age for this Clinical Trial: N/A
Are Healthy Volunteers Accepted for this Clinical Trial: Accepts Healthy Volunteers
Clinical Trial Investigator Information
- Lead Sponsor
- University of Massachusetts, Worcester
- National Institute of Neurological Disorders and Stroke (NINDS)
- Provider of Information About this Clinical Study
- Principal Investigator: Robert Brown, Chair, Neurology – University of Massachusetts, Worcester
- Overall Official(s)
- Robert H Brown Jr., D Phil,MD, Principal Investigator, U Mass Medical School
- Overall Contact(s)
- Diane McKenna-Yasek, RN BSN, 508-856-4697, firstname.lastname@example.org
Citations Reporting on Results
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Blauw HM, Al-Chalabi A, Andersen PM, van Vught PW, Diekstra FP, van Es MA, Saris CG, Groen EJ, van Rheenen W, Koppers M, Van't Slot R, Strengman E, Estrada K, Rivadeneira F, Hofman A, Uitterlinden AG, Kiemeney LA, Vermeulen SH, Birve A, Waibel S, Meyer T, Cronin S, McLaughlin RL, Hardiman O, Sapp PC, Tobin MD, Wain LV, Tomik B, Slowik A, Lemmens R, Rujescu D, Schulte C, Gasser T, Brown RH Jr, Landers JE, Robberecht W, Ludolph AC, Ophoff RA, Veldink JH, van den Berg LH. A large genome scan for rare CNVs in amyotrophic lateral sclerosis. Hum Mol Genet. 2010 Oct 15;19(20):4091-9. Epub 2010 Aug 4.
Ticozzi N, LeClerc AL, Keagle PJ, Glass JD, Wills AM, van Blitterswijk M, Bosco DA, Rodriguez-Leyva I, Gellera C, Ratti A, Taroni F, McKenna-Yasek D, Sapp PC, Silani V, Furlong CE, Brown RH Jr, Landers JE. Paraoxonase gene mutations in amyotrophic lateral sclerosis. Ann Neurol. 2010 Jul;68(1):102-7.
van Es MA, Veldink JH, Saris CG, Blauw HM, van Vught PW, Birve A, Lemmens R, Schelhaas HJ, Groen EJ, Huisman MH, van der Kooi AJ, de Visser M, Dahlberg C, Estrada K, Rivadeneira F, Hofman A, Zwarts MJ, van Doormaal PT, Rujescu D, Strengman E, Giegling I, Muglia P, Tomik B, Slowik A, Uitterlinden AG, Hendrich C, Waibel S, Meyer T, Ludolph AC, Glass JD, Purcell S, Cichon S, Nöthen MM, Wichmann HE, Schreiber S, Vermeulen SH, Kiemeney LA, Wokke JH, Cronin S, McLaughlin RL, Hardiman O, Fumoto K, Pasterkamp RJ, Meininger V, Melki J, Leigh PN, Shaw CE, Landers JE, Al-Chalabi A, Brown RH Jr, Robberecht W, Andersen PM, Ophoff RA, van den Berg LH. Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis. Nat Genet. 2009 Oct;41(10):1083-7. Epub 2009 Sep 6.
Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron DM, Kost JE, Gonzalez-Perez P, Fox AD, Adams J, Taroni F, Tiloca C, Leclerc AL, Chafe SC, Mangroo D, Moore MJ, Zitzewitz JA, Xu ZS, van den Berg LH, Glass JD, Siciliano G, Cirulli ET, Goldstein DB, Salachas F, Meininger V, Rossoll W, Ratti A, Gellera C, Bosco DA, Bassell GJ, Silani V, Drory VE, Brown RH Jr, Landers JE. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature. 2012 Aug 23;488(7412):499-503. doi: 10.1038/nature11280.
González-Pérez P, Cirulli ET, Drory VE, Dabby R, Nisipeanu P, Carasso RL, Sadeh M, Fox A, Festoff BW, Sapp PC, McKenna-Yasek D, Goldstein DB, Brown RH Jr, Blumen SC. Novel mutation in VCP gene causes atypical amyotrophic lateral sclerosis. Neurology. 2012 Nov 27;79(22):2201-8. doi: 10.1212/WNL.0b013e318275963b. Epub 2012 Nov 14.