Delta-2-tubulin as a biomarker and therapeutic target for peripheral neuropathy
The present disclosure relates to delta-2-tubulin and its use as a biomarker for determining if a subject is at risk of developing peripheral neuropathy or if a subject has developed peripheral neuropathy. The present disclosure further relates to methods for the treatment of peripheral neuropathy in a subject and assays for identifying compounds that can be used to treat and/or prevent peripheral neuropathy.
1 . A method for the treatment of chemotherapy-induced peripheral neuropathy in a subject having cancer, the method comprising:
determining an increased level of delta-2-tubulin in a sample of nervous tissue obtained from the subject, and
administering an effective amount of an siRNA or shRNA targeting cytosolic carboxypeptidase 1 (CCP1), cytosolic carboxypeptidase 4 (CCP4), or cytosolic carboxypeptidase 6 (CCP6) or a pharmaceutical composition thereof.
2 . The method of claim 1 , wherein the chemotherapy is selected from the group consisting of oxaliplatin, cisplatin, carboplatin, paclitaxel, eribulin, thalidomide, a taxane, a vinca alkaloid and bortezomib.
3 . The method of claim 2 , wherein the chemotherapy is bortezomib.
4 . The method of claim 1 , wherein the siRNA targets cytosolic carboxypeptidase 1 (CCP1).
5 . The method of claim 1 , wherein the shRNA targets cytosolic carboxypeptidase 1 (CCP1).
6 . The method of claim 1 , wherein the expression level of delta-2-tubulin is determined by immunofluorescence or Western Blot.
7 . The method of claim 1 , wherein the sample comprises one or more peripheral neuronal cells.
8 . The method of claim 1 , wherein the sample is a biopsy of a peripheral nerve.
9 . The method of claim 1 , wherein the sample is a dermal biopsy.