Vancouver – Day two of the Interdependence 2012 Global Spinal Cord Injury Conference. In between sessions at the moment; first, a few things to catch up on from Tuesday.
, whose eponymous foundation and institute sponsored this gathering of the SCI research, rehab, commercial and consumer tribes, made an appearance at a reception last night. No question, Rick is surrounded by a force field of charisma. He shared his dream for an inclusive society and a global SCI research and care network. “Anything is possible,” said the Man in Motion. “Teamwork is the path to achieving our vision of a world without paralysis.”
A few highlights from a Tuesday session called “Advancing Neurogenerative Innovations to Clinical Translation.” Panel included neurosurgeon/researcher Michael Fehlings
, M.D. (pictured on right) /scientist (and Reeve Consortium lab member) James Fawcett
, basic scientist Wolfram Tetzlaff, and scientist/entrepreneur Lisa McKerracher.
Underpinning the discussion, a difficult question: What has to happen before one or more promising strategies is ready to move from animal models to human trials? Good data for efficacy is a key thing, of course, and that may mean proof in a rodent is only a prelude to success in a larger animal model. There are other confounding factors, including dosage and timing, as well as understanding combinations of drugs or therapies. There is also the question of commercialization – the field will go nowhere if industry is not onboard.
Fehlings: described laboratory success with a combo of stem cells and chondroitinase (ch’ase, see more here
) in SCI animal models. “Beautiful migration,” he noted. Appears to be a remyelination strategy. He also reported upbeat results from using “self assembling peptide” scaffolds in SCI models. These are molecules that are injected into the spinal cord as a liquid but form, on their own, a sort of nanofiber network. This leads to neuroprotection, and appears to limit formation of astroglial scarring – which in turn promotes better axon recovery. Pretty cool science story. What is needed: more R&D.
Fawcett: offered a review of “two bits of biology” necessary to understand injury response. The first is that cut axons degenerate and may attempt to grow again but get stuck. Second is the notion of plasticity: cut axons sprout, make short connections between neurons. His point: it may be possible to amp up the plasticity response. He, and many labs, have done that using ch’ase, which breaks down cartilage-like proteins that tie up axons. This works a little on its own but to use the new connections, it’s necessary to learn how. Add rehab and training, the effect is quite good. In rats anyway. What is needed: more data on timing and specificity of training. Wrong training could defeat effect of ch’ase. Also need to figure out how to deliver the drug. A discussion on injections into the spinal cord came later.
Tetzlaff: his point is that the clinical practice guidelines for nutrition after SC I are wrong. The standard diet might be damaging. He has studied dietary restriction – SCI animals improve in function and recovery when they are forced to fast. This kickstarts ketones, a cleaner body fuel than glucose; the idea has been around for 100 years. He’s published these results and promotes it, but doctors don’t seem enthusiastic for the fasting. Tetzlaff recommends the ketogenic diet, which is restricted but not fasting, basically 3 to 1 fat to protein. What is needed: more buy-in from clinicians, figuring out how long to modify diet, predicting interactions with rehab.
McKerracher: she discovered an intercellular pathway in the nervous system related to substances that block regeneration. She found a way to block this, helped found a company and made a drug called Cethrin. We reported on positive results of a Phase I clinical trial
; McKerracher has formed another company in hopes of taking the drug to a larger study. She notes “meaningful recovery over baseline.” Needed: money to run the next phase of trials. There was a question about how she delivers the drug: it is placed in a fibrin material on the surface of the dura (spinal cord lining). The cells figure out how to get into neurons. Wouldn’t it be better just to inject it?
Good question. Why not spinal injection? Earlier, Fawcett noted that in rats the best way to give them ch’ase is by direct injection above and below the lesion site. He noted concern about the safety of this, but said other trials (mainly using stem cells) have injected much larger volumes of molecules than necessary for ch’ase administration.
Fehlings, speaking for the neurosurgical community, predicted there would be ethical concerns in a placebo-controlled clinical trial giving an injection of a dummy drug. There is some risk in penetrating spinal cord tissue.
McKerracher said she too was reluctant to use a sham injection in controls (those not getting the actual dose of Cethrin). However, Charles Tator, physician/researcher from Toronto, commented that he in fact would be willing to use sham injections in a clinical trial. “The questions we need to answer are too important not to.”