Diltiazem Promotes Regenerative Axon Growth

Mol Neurobiol, 2019 · DOI: 10.1007/s12035-018-1349-5 · Published: June 1, 2019

Pharmacology Regenerative Medicine Neurology

Simple Explanation

This research investigates how to encourage nerve cells (neurons) to regrow after injury, which is a major challenge in treating brain and spinal cord damage. The study screened a large number of compounds to find those that could help neurons regenerate in a lab setting, even when faced with obstacles like CSPGs, which inhibit growth. Diltiazem, a drug typically used for heart conditions, was found to promote axon growth in different types of neurons, suggesting it could potentially be repurposed to aid nerve regeneration after injuries.

Study Duration

Not specified

Participants

Rat and mouse cortical, DRG and human sensory neurons

Evidence Level

Not specified

Key Findings

1
Diltiazem, verapamil, and bromopride were identified as compounds that facilitate axon regeneration in rat cortical cultures in the presence of CSPGs.
2
Diltiazem, an L-type calcium channel blocker, promotes axon outgrowth in adult primary mouse dorsal root ganglion (DRG) and induced human sensory (iSensory) neurons.
3
The combination of diltiazem and Y27632 additively enhances axonal growth in the presence of CSPGs, suggesting a potential synergistic effect.

Research Summary

This study aimed to identify pharmacological enhancers of axon regeneration using an in vitro cortical scrape assay. A compound library was screened, and diltiazem, verapamil, and bromopride were found to promote axon regeneration in rat cortical cultures, even with the presence of CSPGs. Further experiments demonstrated that diltiazem, an L-type calcium channel blocker, also promotes axon outgrowth in mouse DRG and induced human sensory neurons, suggesting potential therapeutic applications for nerve regeneration.

Practical Implications

Drug Repurposing

Diltiazem, a clinically approved drug, could be repurposed to promote axon regeneration after CNS injuries.

Therapeutic Target

L-type calcium channels may represent a valuable therapeutic target for developing drugs that enhance axon regeneration.

Combination Therapy

Combining diltiazem with other regeneration-promoting compounds like Y27632 may lead to more effective therapies.

Study Limitations

1
The study primarily used in vitro models, which may not fully replicate the complex environment of the injured CNS.
2
Diltiazem is a P-gp substrate and is rapidly effluxed from the CNS, potentially limiting its effectiveness in vivo.
3
Clinical trials are needed to determine the efficacy and safety of L-CCBs for promoting axon regeneration in humans after CNS injuries.

Your Feedback

Was this summary helpful?

Back to Pharmacology