Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
While doing my paper on Taxol, I came across a molecular basis for the peripheral pain from it. It appears to be caused when the drug binds to a protein and initiates improper calcium signaling, researchers at Yale School of Medicine reported in a study published in the Proceedings of the National Academy of Sciences.
This response leads to side effects such as acute hypersensitivity, slower heart rhythms, tingling, numbness, and other symptoms. These serious side effects limit the drug's effectiveness. Peripheral pain becomes worse with continued use and increased dosages lead to persistent and irreversible pain.
The binding protein is called neuronal calcium sensor (NCS-1). When paclitaxel (taxol) binds to NCS-1, it makes the cell more sensitive to normal signals and increases the magnitude and frequency of changes in calcium. Over time, increased calcium levels activate an enzyme (calpain) that degrades proteins, especially NCS-1.
Calcium signals are needed for nerves to be stimulated and to respond and the loss of NCS-1 makes it more difficult to generate any calcium signals. While the loss of NCS-1 stops the protein interaction that is causing the inappropriate calcium signals, it also decreases the ability to have normal responses (PNAS 104: 11103-11108 June 20, 2007).
Someone had asked, does the intake of calcium in your diet have any bearing on any of this? Believe it or not, the Mayo Clinic has a clinical trial going on using calcium and magnesium in preventing peripheral neuropathy caused by another Bristol-Myers Squibb drugs Ixempra (ixabepilone) in patients with breast cancer (NCT00998738).
http://clinicaltrials.gov/ct2/show/NCT00998738