Combination Therapies: One Plus One May Be Less than Two

[Christopher]

This is an interesting read and makes sense.

The Mayo Clinic neurosurgeons that did 6 different nerve grafts/transfers on me were very concerned about me being overly excited to hit up the Electrical Stim on my muscles too soon (2 months) after surgery. Wanting to not interfere with the body's own regenerative process.

This article validates that concern.

http://communities.kintera.org/REEVE/bl ... 58686.aspx
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One + One May Be Less Than Two

The red pill makes you better. So does the blue one, even though its action is different. So, doesn't it figure that taking red and blue together will make you all the more better? If two or three, or even six or a dozen therapies showed some promise on their own, why not just take everything. Toss in the proverbial kitchen sink.

Of course therapeutic synergy doesn't work that way. Drugs and treatments are by no means additive or complementary. They may interact in unpredictable ways or create new side effects. Drugs in combination may cancel each other out. Polypharmacy could make you worse.

Combination treatment has not yet become an issue in spinal cord injury, but it could as new treatments emerge. An injury to the spinal cord isn't a fast and neat process. After the primary damage to the cord a biochemical process continues for hours, days and even months. This secondary wave includes blood loss, swelling, inflammation and tissue degradation due to a range of toxic cellular events.

While there's not much that can be done about the primary cell loss, at least not in today's clinic, there are strategies to intervene in the secondary cascade to preserve nerve tissue and therefore function. These strategies will require combinations of therapies, timed over months, maybe years, to deal with specific cellular events, long axon growth and guidance, scar reduction, remyelination, and so on. The array of treatments must be carefully sequenced for optimal recovery.

Scientists are already thinking about such combo therapies. Here's a look at a recent study wherein it was postulated that two treatments together would result in a better outcome than either would have alone. The paper was written by a team including Reggie Edgerton of UCLA, and Martin Schwab from the University of Zurich. Both the Edgerton lab and the Schwab lab are part of the Reeve Foundation International Research Consortium on Spinal Cord Injury. The work was funded in part by the Foundation.

One arm measured the effect of Schwab's anti-NOGO-A antibody, the other looked at the effect of treadmill training (underpinned in large part by Edgerton's basic science). Both the antibody and treadmill have been shown separately to enhance recovery after spinal trauma. The antibody does this by neutralizing NOGO, a chemical barrier to nerve growth. Treadmill training is believed to work by using movement to refresh nerve plasticity and thereby unmask latent stepping patterns within the spinal cord.

The anti-NOGO treatment is now in clinical trials in Europe and Canada; it is hoped that the trial will expand next year in the U.S.

The treadmill work is the basis of the Reeve Foundation NeuroRecovery Network.

One group of rats got the anti-NOGO treatment for two weeks following incomplete thoracic spinal cord injuries. Seven days after injury these animals then began training on treadmills five days a week for eight weeks. The combined treatment group was compared to rats that got just the anti-NOGO and to animals that just got treadmill training.

Are the treatments synergistic?

The short answer is no. Animals that had both the antibody and the physical therapy actually showed a diminished functional recovery.

The scientists suggest that as the antibody promoted nerve fiber growth, these fibers may have reestablished pre-injury connections. Meanwhile, however, the treadmill training may have interfered with this process. The two therapies may be competitive.

It may be a matter of timing; the scientists observed that it was better to allow two weeks longer for the regenerative process to rewire the cord before introducing activity-based therapies.

What's next? Says the paper, "The optimal arrangement of combinatorial treatments, e.g. a growth and regeneration enhancing treatment followed by appropriate rehabilitative training remains an exciting challenge for future studies."

In other words, more work to do, hold the sink. Future treatments most certainly will be done in some sort of combination or sequence. It will take a while to sort it out so the whole really is greater than the sum of the parts.

Mad

Published Thursday, June 18, 2009 10:41 PM by maddogz