PMID- 34606118
OWN - NLM
STAT- MEDLINE
DCOM- 20220318
LR  - 20220318
IS  - 1097-4598 (Electronic)
IS  - 0148-639X (Linking)
VI  - 65
IP  - 1
DP  - 2022 Jan
TI  - Nusinersen by subcutaneous intrathecal catheter for symptomatic spinal muscular 
      atrophy patients with complex spine anatomy.
PG  - 51-59
LID - 10.1002/mus.27425 [doi]
AB  - INTRODUCTION/AIMS: Intrathecal administration of nusinersen is challenging in 
      patients with spinal muscular atrophy (SMA) who have spine deformities or 
      fusions. We prospectively studied the safety and efficacy of nusinersen 
      administration via an indwelling subcutaneous intrathecal catheter (SIC) for SMA 
      patients with advanced disease. METHODS: Seventeen participants commenced 
      nusinersen therapy between 2.7 and 31.5 years of age and received 9 to 12 doses 
      via SIC. Safety was assessed in all participants. A separate efficacy analysis 
      comprised 11 nonambulatory, treatment-naive SMA patients (18.1 +/- 6.8 years) with 
      three SMN2 copies and complex spine anatomy. RESULTS: In the safety analysis, 14 
      treatment-related adverse events (AEs) occurred among 12 (71%) participants; all 
      were related to the SIC and not nusinersen. Device-related AEs interfered with 
      2.5% of nusinersen doses. Four SICs (24%) required surgical revision due to 
      mechanical malfunction with or without cerebrospinal fluid leak (n = 2), and one 
      (6%) was removed due to Staphylococcus epidermidis meningitis. In the efficacy 
      analysis, mean performance on the nine-hole peg test improved in dominant (15.9%, 
      P = 0.012) and nondominant (19.0%, P = 0.008) hands and grip strength increased 
      by 44.9% (P = 0.031). We observed no significant changes in motor scales, muscle 
      force, pulmonary function, or SMA biomarkers. All participants in the efficacy 
      cohort reported one or more subjective improvement(s) in endurance, purposeful 
      hand use, arm strength, head control, and/or speech. DISCUSSION: For SMA patients 
      with complex spine anatomy, the SIC allows for reliable outpatient administration 
      of nusinersen that results in meaningful improvements in upper limb function, but 
      introduces risks of technical malfunction and iatrogenic infection.
CI  - (c) 2021 Wiley Periodicals LLC.
FAU - Carson, Vincent J
AU  - Carson VJ
AD  - Clinic for Special Children, Strasburg, Pennsylvania, USA.
FAU - Young, Millie
AU  - Young M
AD  - Clinic for Special Children, Strasburg, Pennsylvania, USA.
FAU - Brigatti, Karlla W
AU  - Brigatti KW
AD  - Clinic for Special Children, Strasburg, Pennsylvania, USA.
FAU - Robinson, Donna L
AU  - Robinson DL
AD  - Clinic for Special Children, Strasburg, Pennsylvania, USA.
FAU - Reed, Robert M
AU  - Reed RM
AD  - University of Maryland School of Medicine, Baltimore, Maryland, USA.
FAU - Sohn, Jihee
AU  - Sohn J
AD  - Biogen, Cambridge, Massachusetts, USA.
FAU - Petrillo, Marco
AU  - Petrillo M
AD  - Biogen, Cambridge, Massachusetts, USA.
FAU - Farwell, Wildon
AU  - Farwell W
AD  - Biogen, Cambridge, Massachusetts, USA.
FAU - Miller, Freeman
AU  - Miller F
AD  - Department of Orthopedics, Sidney Kimmel Medical College at Thomas Jefferson 
      University, Philadelphia, Pennsylvania, USA.
FAU - Strauss, Kevin A
AU  - Strauss KA
AUID- ORCID: 0000-0002-6429-8657
AD  - Clinic for Special Children, Strasburg, Pennsylvania, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211019
PL  - United States
TA  - Muscle Nerve
JT  - Muscle & nerve
JID - 7803146
RN  - 0 (Oligonucleotides)
RN  - 5Z9SP3X666 (nusinersen)
SB  - IM
MH  - Catheters
MH  - Humans
MH  - Injections, Spinal/methods
MH  - *Muscular Atrophy, Spinal/drug therapy
MH  - *Oligonucleotides
OTO - NOTNLM
OT  - nusinersen
OT  - scoliosis
OT  - spinal muscular atrophy
EDAT- 2021/10/05 06:00
MHDA- 2022/03/19 06:00
CRDT- 2021/10/04 12:33
PHST- 2021/09/21 00:00 [revised]
PHST- 2021/05/28 00:00 [received]
PHST- 2021/09/28 00:00 [accepted]
PHST- 2021/10/05 06:00 [pubmed]
PHST- 2022/03/19 06:00 [medline]
PHST- 2021/10/04 12:33 [entrez]
AID - 10.1002/mus.27425 [doi]
PST - ppublish
SO  - Muscle Nerve. 2022 Jan;65(1):51-59. doi: 10.1002/mus.27425. Epub 2021 Oct 19.