Efficacy of epothilones in central nervous system trauma treatment: what has age got to do with it?

Neural Regen Res, 2021 · DOI: https://doi.org/10.4103/1673-5374.295312 · Published: October 9, 2020

Spinal Cord Injury Neurology Brain Injury

Simple Explanation

Central nervous system injuries like traumatic brain and spinal cord injuries lack effective treatments. Epothilones, drugs that stabilize microtubules and can cross the blood-brain barrier, show promise in animal models. However, their effectiveness varies with age, highlighting the need to consider age when using neural regeneration interventions to improve patient outcomes. CNS trauma leads to neuronal cell loss, axonal injury, and glial cell activation. While glial cells can protect against injury spread, they also inhibit axon regeneration. Epothilones can protect axons by stabilizing microtubules, which are often disrupted after injury. Microtubule stabilizing drugs, like epothilones, can affect neuronal and glial populations. At low doses, epothilones protect against microtubule depolarization and encourage structural stability, benefiting axons after injury. Epothilones readily cross the blood-brain barrier, making them an attractive treatment option.

Study Duration

Not specified

Participants

Animal models

Evidence Level

Review

Key Findings

1
Epothilone B (EpoB) therapy following spinal cord injury led to increased axon outgrowth, reduced scarring, and improved functional recovery in female rats.
2
Age plays a critical role in outcomes following CNS trauma and in determining the efficacy of microtubule stabilizers like EpoD.
3
EpoD administration had different effects in young versus adult mice, conferring protection from axonal degeneration in young mice but having a detrimental effect in adult mice.

Research Summary

Central nervous system injury can have significant lasting effects, and there are no comprehensive treatments available. Epothilones, a family of microtubule stabilizing agents, show potential for improving outcomes following experimentally induced trauma. The efficacy of epothilones following traumatic brain injury is dependent upon the age of the animals. A greater emphasis should be placed upon age when using an intervention aimed at neural regeneration. Understanding how age contributes to therapeutic intervention following trauma could pave the way to providing a more tailored therapeutic regime in the clinic that is specific to the age of the patient.

Practical Implications

Tailored Therapeutic Regimes

Age-specific therapeutic interventions are needed for CNS trauma, considering the varied effects of drugs like epothilones across different age groups.

Importance of Age in Preclinical Trials

Preclinical trials for CNS trauma therapies should account for the effect of age to improve the translatability of promising drugs to clinical settings.

Further Research on Microtubule Stabilization

Future studies should focus on how the efficacy of therapeutic microtubule stabilization changes across the lifespan to optimize treatment strategies.

Study Limitations

1
Narrow selection criteria used for the review.
2
Other variables should be considered to gain a greater understanding on age dependant CNS trauma and therapeutic targeting.
3
The response of the CNS to trauma can be sex-dependent - how this affects therapeutic intervention outcomes is largely unexplored.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury