Defining SOD1 ALS natural history to guide therapeutic clinical trial design

Taha Bali, Wade Self, Jingxia Liu, Teepu Siddique, Leo H. Wang, Thomas D. Bird, Elena Ratti, Nazem Atassi, Kevin B. Boylan, Jonathan D. Glass, Nicholas J Maragakis, James B. Caress, Leo F. McCluskey, Stanley H. Appel, James P. Wymer, Summer Gibson, Lorne Zinman, Tahseen Mozaffar, Brian Callaghan, April L. McVeyJennifer Jockel-Balsarotti, Peggy Allred, Elena R. Fisher, Glenn Lopate, Alan Pestronk, Merit E. Cudkowicz, Timothy M. Miller

Research output: Contribution to journalArticle

Abstract

Importance Understanding the natural history of familial amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALSSOD1) will provide key information for optimising clinical trials in this patient population. Objective To establish an updated natural history of ALSSOD1. Design, setting and participants Retrospective cohort study from 15 medical centres in North America evaluated records from 175 patients with ALS with genetically confirmed SOD1 mutations, cared for after the year 2000. Main outcomes and measures Age of onset, survival, ALS Functional Rating Scale (ALS-FRS) scores and respiratory function were analysed. Patients with the A4V (Ala-Val) SOD1 mutation (SOD1A4V), the largest mutation population in North America with an aggressive disease progression, were distinguished from other SOD1 mutation patients (SOD1non-A4V) for analysis. Results Mean age of disease onset was 49.7 ±12.3 years (mean±SD) for all SOD1 patients, with no statistical significance between SOD1A4V and SOD1non-A4V (p=0.72, Kruskal-Wallis). Total SOD1 patient median survival was 2.7 years. Mean disease duration for all SOD1 was 4.6±6.0 and 1.4±0.7 years for SOD1A4V. SOD1A4V survival probability (median survival 1.2 years) was significantly decreased compared with SOD1non-A4V (median survival 6.8 years; p

Original languageEnglish (US)
JournalJournal of Neurology, Neurosurgery and Psychiatry
DOIs
StateAccepted/In press - Jun 3 2016

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Amyotrophic Lateral Sclerosis
Natural History
Clinical Trials
Mutation
Survival
North America
Age of Onset
Therapeutics
Population
Disease Progression
Cohort Studies
Retrospective Studies
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Surgery
  • Arts and Humanities (miscellaneous)

Cite this

Bali, T., Self, W., Liu, J., Siddique, T., Wang, L. H., Bird, T. D., ... Miller, T. M. (Accepted/In press). Defining SOD1 ALS natural history to guide therapeutic clinical trial design. Journal of Neurology, Neurosurgery and Psychiatry. https://doi.org/10.1136/jnnp-2016-313521

Defining SOD1 ALS natural history to guide therapeutic clinical trial design. / Bali, Taha; Self, Wade; Liu, Jingxia; Siddique, Teepu; Wang, Leo H.; Bird, Thomas D.; Ratti, Elena; Atassi, Nazem; Boylan, Kevin B.; Glass, Jonathan D.; Maragakis, Nicholas J; Caress, James B.; McCluskey, Leo F.; Appel, Stanley H.; Wymer, James P.; Gibson, Summer; Zinman, Lorne; Mozaffar, Tahseen; Callaghan, Brian; McVey, April L.; Jockel-Balsarotti, Jennifer; Allred, Peggy; Fisher, Elena R.; Lopate, Glenn; Pestronk, Alan; Cudkowicz, Merit E.; Miller, Timothy M.

In: Journal of Neurology, Neurosurgery and Psychiatry, 03.06.2016.

Research output: Contribution to journalArticle

Bali, T, Self, W, Liu, J, Siddique, T, Wang, LH, Bird, TD, Ratti, E, Atassi, N, Boylan, KB, Glass, JD, Maragakis, NJ, Caress, JB, McCluskey, LF, Appel, SH, Wymer, JP, Gibson, S, Zinman, L, Mozaffar, T, Callaghan, B, McVey, AL, Jockel-Balsarotti, J, Allred, P, Fisher, ER, Lopate, G, Pestronk, A, Cudkowicz, ME & Miller, TM 2016, 'Defining SOD1 ALS natural history to guide therapeutic clinical trial design', Journal of Neurology, Neurosurgery and Psychiatry. https://doi.org/10.1136/jnnp-2016-313521
Bali, Taha ; Self, Wade ; Liu, Jingxia ; Siddique, Teepu ; Wang, Leo H. ; Bird, Thomas D. ; Ratti, Elena ; Atassi, Nazem ; Boylan, Kevin B. ; Glass, Jonathan D. ; Maragakis, Nicholas J ; Caress, James B. ; McCluskey, Leo F. ; Appel, Stanley H. ; Wymer, James P. ; Gibson, Summer ; Zinman, Lorne ; Mozaffar, Tahseen ; Callaghan, Brian ; McVey, April L. ; Jockel-Balsarotti, Jennifer ; Allred, Peggy ; Fisher, Elena R. ; Lopate, Glenn ; Pestronk, Alan ; Cudkowicz, Merit E. ; Miller, Timothy M. / Defining SOD1 ALS natural history to guide therapeutic clinical trial design. In: Journal of Neurology, Neurosurgery and Psychiatry. 2016.
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abstract = "Importance Understanding the natural history of familial amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALSSOD1) will provide key information for optimising clinical trials in this patient population. Objective To establish an updated natural history of ALSSOD1. Design, setting and participants Retrospective cohort study from 15 medical centres in North America evaluated records from 175 patients with ALS with genetically confirmed SOD1 mutations, cared for after the year 2000. Main outcomes and measures Age of onset, survival, ALS Functional Rating Scale (ALS-FRS) scores and respiratory function were analysed. Patients with the A4V (Ala-Val) SOD1 mutation (SOD1A4V), the largest mutation population in North America with an aggressive disease progression, were distinguished from other SOD1 mutation patients (SOD1non-A4V) for analysis. Results Mean age of disease onset was 49.7 ±12.3 years (mean±SD) for all SOD1 patients, with no statistical significance between SOD1A4V and SOD1non-A4V (p=0.72, Kruskal-Wallis). Total SOD1 patient median survival was 2.7 years. Mean disease duration for all SOD1 was 4.6±6.0 and 1.4±0.7 years for SOD1A4V. SOD1A4V survival probability (median survival 1.2 years) was significantly decreased compared with SOD1non-A4V (median survival 6.8 years; p",
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T1 - Defining SOD1 ALS natural history to guide therapeutic clinical trial design

AU - Bali, Taha

AU - Self, Wade

AU - Liu, Jingxia

AU - Siddique, Teepu

AU - Wang, Leo H.

AU - Bird, Thomas D.

AU - Ratti, Elena

AU - Atassi, Nazem

AU - Boylan, Kevin B.

AU - Glass, Jonathan D.

AU - Maragakis, Nicholas J

AU - Caress, James B.

AU - McCluskey, Leo F.

AU - Appel, Stanley H.

AU - Wymer, James P.

AU - Gibson, Summer

AU - Zinman, Lorne

AU - Mozaffar, Tahseen

AU - Callaghan, Brian

AU - McVey, April L.

AU - Jockel-Balsarotti, Jennifer

AU - Allred, Peggy

AU - Fisher, Elena R.

AU - Lopate, Glenn

AU - Pestronk, Alan

AU - Cudkowicz, Merit E.

AU - Miller, Timothy M.

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N2 - Importance Understanding the natural history of familial amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALSSOD1) will provide key information for optimising clinical trials in this patient population. Objective To establish an updated natural history of ALSSOD1. Design, setting and participants Retrospective cohort study from 15 medical centres in North America evaluated records from 175 patients with ALS with genetically confirmed SOD1 mutations, cared for after the year 2000. Main outcomes and measures Age of onset, survival, ALS Functional Rating Scale (ALS-FRS) scores and respiratory function were analysed. Patients with the A4V (Ala-Val) SOD1 mutation (SOD1A4V), the largest mutation population in North America with an aggressive disease progression, were distinguished from other SOD1 mutation patients (SOD1non-A4V) for analysis. Results Mean age of disease onset was 49.7 ±12.3 years (mean±SD) for all SOD1 patients, with no statistical significance between SOD1A4V and SOD1non-A4V (p=0.72, Kruskal-Wallis). Total SOD1 patient median survival was 2.7 years. Mean disease duration for all SOD1 was 4.6±6.0 and 1.4±0.7 years for SOD1A4V. SOD1A4V survival probability (median survival 1.2 years) was significantly decreased compared with SOD1non-A4V (median survival 6.8 years; p

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