Prospective cohort study of spinal muscular atrophy types 2 and 3.
OBJECTIVE
To characterize the natural history of spinal muscular atrophy type 2 and type 3 (SMA 2/3) beyond 1 year and to report data on clinical and biological outcomes for use in trial planning.


METHODS
We conducted a prospective observational cohort study of 79 children and young adults with SMA 2/3 who participated in evaluations for up to 48 months. Clinically, we evaluated motor and pulmonary function, quality of life, and muscle strength. We also measured SMN2 copy number, hematologic and biochemical profiles, muscle mass by dual x-ray absorptiometry (DXA), and the compound motor action potential (CMAP) in a hand muscle. Data were analyzed for associations between clinical and biological/laboratory characteristics cross-sectionally, and for change over time in outcomes using all available data.


RESULTS
In cross-sectional analyses, certain biological measures (specifically, CMAP, DXA fat-free mass index, and SMN2 copy number) and muscle strength measures were associated with motor function. Motor and pulmonary function declined over time, particularly at time points beyond 12 months of follow-up.


CONCLUSIONS
The intermediate and mild phenotypes of SMA show slow functional declines when observation periods exceed 1 year. Whole body muscle mass, hand muscle compound motor action potentials, and muscle strength are associated with clinical measures of motor function. The data from this study will be useful for clinical trial planning and suggest that CMAP and DXA warrant further evaluation as potential biomarkers.
Department of Neurology, Columbia University, New York, USA.
Petra
P
Kaufmann
Michael P
MP
McDermott
Basil T
BT
Darras
Richard S
RS
Finkel
Douglas M
DM
Sproule
Peter B
PB
Kang
Maryam
M
Oskoui
Andrei
A
Constantinescu
Clifton L
CL
Gooch
A Reghan
AR
Foley
Michele L
ML
Yang
Rabi
R
Tawil
Wendy K
WK
Chung
William B
WB
Martens
Jacqueline
J
Montes
Vanessa
V
Battista
Jessica
J
O'Hagen
Sally
S
Dunaway
Jean
J
Flickinger
Janet
J
Quigley
Susan
S
Riley
Allan M
AM
Glanzman
Maryjane
M
Benton
Patricia A
PA
Ryan
Mark
M
Punyanitya
Megan J
MJ
Montgomery
Jonathan
J
Marra
Benjamin
B
Koo
Darryl C
DC
De Vivo
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D009048:Motor Skills / Q000502:physiology*; D053580:Muscle Strength / Q000502:physiology*; D011446:Prospective Studies; D011788:Quality of Life; D015656:Respiratory Mechanics / Q000502:physiology*; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics / Q000503:physiopathology*; D055815:Young Adult