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Updated: May 6, 2026
Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity
Published on: April 26, 2012
Potential of histone deacetylase 6 inhibitors in alleviating chemotherapy-induced peripheral neuropathy
Su Jung Park1, Soung-Min Lee2, Seong Mook Kang1
1Discovery Biology Group I, CKD Research Institute, CKD Pharmaceutical Co, Yongin, Korea.
Background:
Histone deacetylase 6 (HDAC6), belonging to class IIb of histone deacetylases, regulates the acetylation of the cytoplasmic protein α-tubulin. The overexpression of HDAC6 is linked to the development of tumors, and inhibiting HDAC6 is known to trigger apoptosis in multiple myeloma cells. In addition to its application in cancer treatment, bortezomib, a proteasome inhibitor, is widely used in managing multiple myeloma and has shown effectiveness in patients with both newly diagnosed and relapsed disease. However, the treatment regimen may be delayed or discontinued due to the risk of peripheral neuropathy, a significant non-hematologic side effect.
Methods:
Animal models of peripheral neuropathy induced by various anti-cancer drugs were established, confirming the potential of HDAC6 inhibitors as a treatment for this condition. Six- to eight-week-old male Sprague Dawley rats were utilized to create these models. Mechanical allodynia and electron microscopy served as indicators of peripheral neuropathy. The HDAC6 inhibitor CKD-011 was administered at doses of 5, 10, 20, and 40 mg/kg.
Results:
In an animal model of bortezomib-induced peripheral neuropathy, CKD-011, an HDAC6 inhibitor, effectively ameliorated peripheral neuropathy. Similarly, CKD-011 administration demonstrated recovery from peripheral neuropathy in models induced with oxaliplatin, paclitaxel, and cisplatin.
Conclusions:
These findings suggest that HDAC6 inhibitors have the potential to mitigate peripheral neuropathy induced by chemotherapeutic agents.
Insights
Histone deacetylase 6 (HDAC6) inhibitors show promise in treating chemotherapy-induced peripheral neuropathy. This study demonstrates that HDAC6 inhibition effectively ameliorates neuropathy in animal models, offering a potential therapeutic strategy.
Area of Science:
- Oncology
- Neuroscience
- Pharmacology
Background:
- Histone deacetylase 6 (HDAC6) regulates cytoplasmic protein acetylation and is implicated in tumor development.
- HDAC6 inhibition induces apoptosis in multiple myeloma cells.
- Bortezomib, a proteasome inhibitor used for multiple myeloma, can cause peripheral neuropathy, a dose-limiting side effect.
Purpose of the Study:
- To investigate the potential of HDAC6 inhibitors in mitigating chemotherapy-induced peripheral neuropathy.
- To evaluate the efficacy of the HDAC6 inhibitor CKD-011 in animal models of peripheral neuropathy.
Main Methods:
- Animal models of peripheral neuropathy were established using chemotherapeutic agents like bortezomib, oxaliplatin, paclitaxel, and cisplatin.
- Mechanical allodynia and electron microscopy were used to assess neuropathy.
- The HDAC6 inhibitor CKD-011 was administered at various doses (5, 10, 20, 40 mg/kg).
Main Results:
- CKD-011 significantly ameliorated bortezomib-induced peripheral neuropathy in rats.
- CKD-011 also demonstrated efficacy in reversing neuropathy induced by oxaliplatin, paclitaxel, and cisplatin.
Conclusions:
- HDAC6 inhibitors represent a potential therapeutic approach to manage peripheral neuropathy caused by chemotherapeutic agents.
- These findings support further investigation into HDAC6 inhibitors for preventing or treating chemotherapy-induced nerve damage.
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