A groundbreaking study published in Current Pharmaceutical Analysis has uncovered a potential therapeutic target for bortezomib-induced peripheral neuropathy (BIPN), a common and debilitating side effect of bortezomib treatment in multiple myeloma patients.
The research, led by Dr. Yunlong Tang and colleagues, utilized lipidomics and computational analyses to identify significant changes in cardiolipin metabolism, a critical mitochondrial phospholipid, in patients suffering from BIPN.
The study involved serum lipidomic profiling of 37 multiple myeloma patients, revealing substantial mitochondrial cardiolipin dysregulation in those with BIPN. Animal models treated with bortezomib exhibited reduced cardiolipin levels in blood and spinal cord tissues, alongside neuronal damage. “Our findings suggest that bortezomib disrupts cardiolipin synthesis and transport, leading to mitochondrial dysfunction and neuronal damage,” said Dr. Tang.
The researchers also conducted virtual screening of FDA-approved drugs targeting cardiolipin-related proteins, identifying diosmin as a promising candidate. Molecular dynamics simulations confirmed stable binding of diosmin to a key enzyme, PGS1, involved in cardiolipin synthesis. “Identifying cardiolipin abnormalities as a contributor to BIPN opens new avenues for therapeutic intervention,” Dr. Tang added.
This study not only enhances the understanding of BIPN pathogenesis but also provides a theoretical basis for developing targeted therapies to mitigate this side effect. Future research will focus on validating these findings in larger cohorts and exploring the clinical potential of cardiolipin-targeted interventions.
Journal
Current Pharmaceutical Analysis