Delta-2-tubulin as a biomarker and therapeutic target for peripheral neuropathy
Inventors
Bartolini, Francesca • Pero, Maria Elena • Cavaletti, Guido
Assignees
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Publication Number
US-12663425-B2
Publication Date
2026-06-23
Expiration Date
Abstract
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.
Core Innovation
The disclosure centers on delta-2-tubulin (D2-tubulin) as a biomarker and functional mediator in chemotherapy-induced peripheral neuropathy (CIPN). It describes using increased delta-2-tubulin expression after exposure to anti-cancer agents to assess risk and diagnosis of peripheral neuropathy, and monitoring delta-2-tubulin localization and changes after drug treatment.
The document further proposes treating and/or preventing CIPN by targeting delta-2-tubulin-associated pathways. In particular, it describes administering delta-2-tubulin inhibitors, including RNAi/shRNA/antisense targeting cytosolic carboxypeptidase 1 (CCP1), cytosolic carboxypeptidase 4 (CCP4), or cytosolic carboxypeptidase 6 (CCP6), and modulation via tubulin tyrosine ligase (TTL). The stated mechanism connects tubulin post-translational modification, microtubule dynamics, and downstream effects such as axonopathy and mitochondrial motility.
Assays are described to identify therapeutic compounds and cancer agents with reduced neuropathy risk. These assays involve monitoring delta-2-tubulin expression and related changes after drug treatment, and include evaluation of delta-2-tubulin localization. The document also describes related kit and pharmaceutical composition concepts connected to measuring delta-2-tubulin and administering therapeutic agents.
Claims Coverage
The provided independent claim covers 2 inventive features: determination of increased delta-2-tubulin level in a nervous tissue sample, and administration of an siRNA or shRNA therapy targeting CCP1, CCP4, or CCP6 for CIPN treatment.
Delta-2-tubulin level determination in nervous tissue sample
Determining an increased level of delta-2-tubulin in a sample of nervous tissue obtained from the subject.
SiRNA or shRNA targeting CCP1, CCP4, or CCP6 for CIPN treatment
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.
The independent claim combines increased delta-2-tubulin determination in a nervous tissue sample with administration of an effective amount of siRNA or shRNA targeting CCP1, CCP4, or CCP6 to treat chemotherapy-induced peripheral neuropathy.
Stated Advantages
Documented Applications
Assessing risk/diagnosis of chemotherapy-induced peripheral neuropathy by monitoring increased delta-2-tubulin expression after exposure to anti-cancer agents in nervous tissue samples.
Treatment and/or prevention of chemotherapy-induced peripheral neuropathy by administering siRNA or shRNA targeting CCP1, CCP4, or CCP6 (or a pharmaceutical composition thereof) in subjects having cancer.
Identifying therapeutic compounds and cancer agents with reduced neuropathy risk by monitoring delta-2-tubulin expression, localization, and changes after drug treatment.
Using delta-2-tubulin measurement approaches associated with kits and pharmaceutical compositions for related workflows.
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