Painful Nerve Condition May Be Improved By Blocking Protein

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Painful Nerve Condition May Be Improved By Blocking Protein

http://www.medicalnewstoday.com/articles/142503.php

Scientists have identified the first gene that pulls the plug on ailing nerve

cell branches from within the nerve cell, possibly helping to trigger the

painful condition known as neuropathy.

The condition is a side effect of some forms of chemotherapy and can also

afflict patients with cancer, diabetes, kidney failure, viral infections,

neurodegenerative disorders and other ailments.

Researchers at Washington University School of Medicine in St. Louis showed that

blocking the dual leucine zipper kinase (DLK) gene inhibits degeneration of

ailing nerve cell branches, possibly preventing neuropathy.

" Neuropathy can become so extraordinarily painful that some patients stop taking

their chemotherapy, regardless of the consequences in their fight against

cancer, " says co-senior author Di, M.D., Ph.D., associate professor

of developmental biology. " So we're very excited about the possibilities this

gene may offer for reducing that pain. "

The findings are published online on March 15 in Nature Neuroscience.

Scientists have known since 1850 that nerve cells have ways to prune branches

(also known as axons) that are injured. Although axon pruning is also a normal

part of early human development, inappropriate loss of axons in the adult

nervous system causes painful sensations that have been compared to burning,

freezing or electric shock and have come to be known as neuropathy.

Di's lab previously revealed that the fruit fly's version of DLK helps

establish synapses, junctures where two nerve cells communicate. But they found

the gene doesn't do the same thing in mice.

Curious about DLK's role in mammals, Bradley , an M.D./Ph.D. student in

Di's lab, consulted with co-senior author Milbrandt, M.D., Ph.D.,

the Clayson Professor of Neurology. Milbrandt studies the role of various

proteins in neurodegeneration. With support from the University's Hope Center

for Neurological Disorders, they showed that the long axons of the sciatic nerve

in mice with a mutated DLK gene resisted degeneration after it was surgically

cut.

In follow-up tests, and Craig Press, an M.D./Ph.D. student in Milbrandt's

lab, took nerve cells in culture and treated their axons with the chemotherapy

drug vincristine. Normal axons degenerated rapidly after exposure to the drug,

but axons where DLK's activity had been blocked were protected from

degeneration.

" The pain of neuropathy is often a key factor that limits the dose in cancer

chemotherapy, " Di notes. " We know when patients are going to start their

treatment, so one day it might be possible to start patients on a DLK-blocking

drug before their chemotherapy and spare them considerable pain. "

DLK appears to act like a contractor that calls in wrecking crews, Di

notes. It helps make the decision to eradicate an axon, but the actual

demolition is left to other processes called up by DLK.

" We want to more fully understand the chain of molecular reactions that carry

out DLK's decision, because that might reveal a better opportunity to block the

effect with a drug, " says Di.

Di and Milbrandt also plan to test if blocking DLK stops

neurodegeneration in other forms of injury and stress, including the harm

inflicted on the optic nerve by glaucoma and central nervous system phenomena

like stroke and Parkinson's disease.