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November 30, 2009BMC NeuroscienceOpen Access

Subcutaneous administration of TC007 reduces disease severity in an animal model of SMA

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Key result

TC007 improves motor function and muscle size in SMA mice but fails to extend lifespan.

  • 16% longer
  • P not significant
  • n=40

Why the study?

Does subcutaneous administration of TC007 improve survival and disease severity in an animal model of SMA?

Population

Intermediate Spinal Muscular Atrophy mouse model, n=40.

Comparison

TC007 30 mg/kg daily via subcutaneous injection… vs PBS via subcutaneous injection from post-natal…

Design

Preclinical

Follow-up

Until death (median 17.5 to 19 days)

Authors

VMVirginia B. MattisMFMarina Y. FossoCCCheng‐Wei Tom Chang

Discussion

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Overview

May improve motor function without survival benefit in SMA mice; hypothesis-generating for CNS-penetrant read-through compounds.

Structured PICO

Does subcutaneous administration of TC007 improve survival and disease severity in an animal model of SMA?

P
Population
40 intermediate SMA model mice (Smn-/-; SMN2+/+; SMNΔ7) treated from post-natal day 2 to 15 to evaluate the effects of TC007.
I
Intervention
TC007 30 mg/kg daily via subcutaneous injection from post-natal day 2 to 15.
C
Comparator
PBS (vehicle) via subcutaneous injection from post-natal day 2 to 15.
O
Outcome
Lifespan (survival).hard clinical

Main Result

Effect estimate: 16% longer

Absolute Event Rate: 18.25% vs 15.75%

p-value: p=not significant

Subcutaneous administration of the read-through compound TC007 improves gross motor function and muscle fiber size in an SMA mouse model but does not significantly extend survival, likely due to poor CNS penetrance.

Limitations

  • Did not significantly extend survival
  • No significant increase in steady-state levels of SMN protein detected in brain, spinal cord, or muscle
  • Blood-brain-barrier permeability and pharmacokinetics have not been examined for TC007
  • TC007 lacks properties typically associated with drugs for CNS disorders, such as blood-brain-barrier permeability.
  • In vivo examination did not correlate with in vitro activity under these experimental conditions.

Cite This Study

Mattis et al. (2009) studied Spinal Muscular Atrophy (SMA) (n=40). TC007 vs. Vehicle (PBS) was evaluated on Lifespan (16% longer, p=not significant). Subcutaneous administration of TC007 to SMA mice improved gross motor function and muscle fiber size, but did not significantly extend average lifespan (18.25 days vs 15.75 days).

synapsesocial.com/papers/6aa36b57240321efda554addhttps://doi.org/10.1186/1471-2202-10-142
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Efficient SMN Rescue following Subcutaneous Tricyclo-DNA Antisense Oligonucleotide Treatment2017 · 40 citations
  2. 2Analysis of Azithromycin Monohydrate as a Single or a Combinatorial Therapy in a Mouse Model of Severe Spinal Muscular Atrophy2017 · 19 citations
  3. 3Discovery of a CNS penetrant small molecule SMN2 splicing modulator with improved tolerability for spinal muscular atrophy2020 · 39 citations
  4. 4SMN2 as a therapeutic target in spinal muscular atrophy: advances in gene expression modulation2025 · 3 citations
  5. 5Antisense oligonucleotides treatment uncovers differences in the modulation of dysregulated intracellular pathways in Spinal Muscular Atrophy motoneurons2026