Targeting neurotrophin and nitric oxide signaling to treat spinal cord injury and associated neurogenic bladder overactivity

Continence (Amst), 2022 · DOI: 10.1016/j.cont.2022.100014 · Published: March 1, 2022

Simple Explanation

Spinal cord injury (SCI) often leads to lower urinary tract dysfunction (LUTD). Current treatments don't fully restore function, creating a need for new therapeutic targets. This study explores using multiple drugs to target different stages of SCI and LUTD pathology to promote recovery of mobility and bladder function. The approach involves a combination of drugs that protect nerve cells, promote neural remodeling, and enhance blood vessel formation at the injury site.

Study Duration

42 days

Participants

Adult female and male C57Bl/6 mice (8–12 weeks)

Evidence Level

Not specified

Key Findings

1
LM11A-31, administered early after SCI, promoted functional recovery and nerve fiber sparing, as shown by MRI and diffusion tensor imaging.
2
LM22B-10 improved hindlimb function and ameliorated neurogenic bladder dysfunction in SCI mice.
3
Cinaciguat improved mitochondrial respiration in SCI mice, suggesting a neuroprotective effect by enhancing blood vessel formation.

Research Summary

This study investigates a multipronged approach to treating spinal cord injury (SCI) and associated lower urinary tract dysfunction (LUTD) by targeting different signaling pathways at various time points after injury. The researchers used small molecule drugs—LM11A-31, LM22B-10, and cinaciguat—to inhibit apoptosis, promote neural growth and survival, and support angiogenesis/repair in a mouse model of SCI. The findings suggest that this combination therapy can improve functional outcomes, including mobility and bladder function, after SCI by addressing the complex and time-dependent nature of the injury.

Practical Implications

Clinical Translation

The study supports the translational potential of the proposed drugs for enhancing functional recovery following SCI. LM11A-31 and cinaciguat have already passed phase I and IIa clinical trials.

Adaptive Treatment

The research highlights the importance of adaptive treatment strategies that target multiple signaling pathways at critical time points after SCI, rather than a one-size-fits-all approach.

Drug Combinations

Further investigations are required into combination treatments that provide neurotrophic support and revascularization with the aim to improve recovery of mobility and bladder functions.

Study Limitations

1
Further investigation is needed to determine the optimal duration of LM22B-10 treatment beyond 28 days.
2
The study focused on a mouse model, and results may not directly translate to humans.
3
More research is required to understand the long-term effects and potential side effects of the drug combination.

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