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 language | English (US) |
|---|---|
| Journal | Journal of Neurology, Neurosurgery and Psychiatry |
| DOIs | |
| State | Accepted/In press - Jun 3 2016 |
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ASJC Scopus subject areas
- Clinical Neurology
- Psychiatry and Mental health
- Surgery
- Arts and Humanities (miscellaneous)
Cite this
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 journal › Article
}
TY - JOUR
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.
PY - 2016/6/3
Y1 - 2016/6/3
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
AB - 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
UR - http://www.scopus.com/inward/record.url?scp=84973352601&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84973352601&partnerID=8YFLogxK
U2 - 10.1136/jnnp-2016-313521
DO - 10.1136/jnnp-2016-313521
M3 - Article
C2 - 27261500
AN - SCOPUS:84973352601
JO - Journal of Neurology, Neurosurgery and Psychiatry
JF - Journal of Neurology, Neurosurgery and Psychiatry
SN - 0022-3050
ER -