Multiple Sclerosis Drug Could Reduce Painful Side Effects of Common Cancer Treatment
Researchers from Saint Louis University School of Medicine have discovered why many
multiple myeloma patients experience severe pain when treated with the anticancer
drug bortezomib. The study, which was published on April 27 in the Journal of Experimental Medicine, suggests that a drug already approved to treat multiple sclerosis could mitigate
this effect and allow myeloma patients to successfully complete their treatment.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common, painful side effect
of many anticancer drugs that can cause patients to discontinue treatment or, because
symptoms can persist for years, reduce the quality of life for cancer survivors.
“This growing problem is a major unmet clinical need, because the increased efficacy
of cancer therapy has resulted in nearly 14 million cancer survivors in the United
States, many suffering from the long-term side effects of CIPN,” says Daniela Salvemini,
Ph.D. professor of pharmacology and physiology at Saint Louis University School of
Bortezomib, which is widely used to treat multiple myeloma and mantle cell lymphoma,
causes CIPN in over 40% of patients but the reasons for this are unclear. Salvemini
and colleagues found that bortezomib accelerates the production of a class of molecules
called sphingolipids that have previously been linked to neuropathic pain. Rats treated
with bortezomib began to accumulate two sphingolipid metabolites, sphingosine 1-phosphate
and dihydrosphingosine 1-phosphate, in their spinal cords at the time that they began
to show signs of neuropathic pain. Blocking the production of these molecules prevented
the animals from developing CIPN in response to bortezomib.
Sphingosine 1-phosphate and dihydrosphingosine 1-phosphate can activate a cell surface
receptor protein called S1PR1. Salvemini and colleagues determined that the two metabolites
cause CIPN by activating S1PR1 on the surface of specialized nervous system support
cells called astrocytes, resulting in neuroinflammation and enhanced release of the
excitatory neurotransmitter glutamate.
Drugs that inhibit S1PR1 also prevented rats from developing CIPN in response to bortezomib.
One such inhibitor was fingolimod, an orally administered drug approved to treat multiple
sclerosis. Importantly, fingolimod did not inhibit bortezomib’s ability to kill myeloma
cells. Indeed, fingolimod itself has been reported to inhibit tumor growth and enhance
the effects of bortezomib.
“Because fingolimod shows promising anticancer potential and is already FDA-approved,
we think that our findings in rats can be rapidly translated to the clinic to prevent
and treat bortezomib-induced neuropathic pain,” said Salvemini.
Established in 1836, Saint Louis University School of Medicine has the distinction
of awarding the first medical degree west of the Mississippi River. The school educates
physicians and biomedical scientists, conducts medical research, and provides health
care on a local, national and international level. Research at the school seeks new
cures and treatments in five key areas: cancer, liver disease, heart/lung disease,
aging and brain disease, and infectious diseases.