A Repair Affair
New studies aim to counter old
spinal cord habits.

Marie Filbin has spent much of the last decade fighting nature. Not in a tabloid newspaper way, but on a more intimate level, in spinal cords injured by trauma or by disease such as ALS. Nerves in the body’s periphery—legs, feet and such—are fortunately able to regenerate after damage, although slowly. But the spinal cord is unusual, says Filbin, a Hunter College bioscientist and Center grantee. When injured, as ALS patients know, spinal cord neurons typically fade away. And Filbin hopes to counter that.

What accounts for the difference in nerve salvageability? Several things. And chief among them, she says, is the central nervous system’s damping down of a natural repair pathway—the same one activated when outlying sensory or motor nerves are damaged. It’s that pathway Filbin studies. And it’s one she’d like to be able to switch on in times of spinal cord injury.

“We want to encourage damaged or degenerating nerves to regrow,” she explains. “Then we’ll be ready to step in when ALS is finally blocked. Plus, there’s a chance that repair techniques we find could protect cells even as the disease is going on.”

So far, Filbin has isolated three molecules that stop neuron growth. All three are found in myelin, neurons’ fatty insulating material. And they all act at roughly the same spot to squelch the nerve cell repair pathway. Filbin’s team has worked steadily to find agents that knock the molecules out of commission—to inhibit the inhibitors. Part of her Packard funding has gone to test those agents in motor neuron cultures. So far, they’ve successfully gotten the neurons to grow despite the inhibitors.

But, perhaps even more effective is a tactic that skirts inhibition altogether. By mapping the inhibitory path, Filbin has found a natural override—a way to keep it from being turned on in the first place. It involves raising levels of polyamines, key molecules that nudge cells to begin dividing. You accomplish that, Filbin says, by adding polyamine-catalyzing genes to neurons. Now her lab has eagerly jumped into spinal cord repair, showing that higher levels of polyamines do indeed encourage growth in spinal cord cultures.

The next step goes beyond mere cultures. Now Filbin’s focus is on embryonic stem (ES) cells—those able to morph into motor neurons inside the spinal cord. By adding polyamine-prompting genes to ES cells, her team hopes to get healthy, robust nerve cells tailored from the start to overcome spinal cord nay-saying.

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Taking stock of the Packard Center as we enter into our fourth year.