I was at Working to Walk (W2W) last week. That’s an annual gathering of “cure warriors.”



Some of the more militant troops remind me of “cure not care” Charles Carson, founder of the Spinal Cord Society – the first cure advocacy group dating to the late 1970s. Chuck, who died a year ago, believed that science and medicine could fix SCI with a focused effort. He used to suggest cure research would happen more quickly if scientists were given epidural nerve blocks to induce paralysis – to sharpen the sense of urgency. He also used to wonder whether progress was impeded by the rehab and caring industries, whose bottom line would suffer if people started dumping their wheelchairs. Carson used to host an annual SCS convention, set up much like W2W. Scientists meet the consumers. Even in the most incomprehensible neuro-babble, there is hope. As Carson often said, “A lot more people have died from no hope than from false hope.”

The biggest difference now as opposed to 30 years ago: the warriors are much better informed. And they all seem to know each other, thanks to a networked world. There is more hope now, or at least there are more clinical trials. Better biology and more shoulders to the wheel. But today there's still just as much impatience, passion, and anger as there was in Chuck's day.

The two-day W2W event, this year held in Rockville, MD, featured a slate of scientific talks and less formal breakouts. You can watch some of them here, and you can get the general drift from a cursory blog overview, written in real time by Kate Willett.

Interesting meeting. The first speaker was R. Douglas Fields, an NIH scientist, blogger and author of the book “The Other Brain: From Dementia to Schizophrenia, How New Discoveries about the Brain Are Revolutionizing Medicine and Science.” It’s all about glial cells, which make up 85 percent of the central nervous system and were once thought to be just the bubble wrap around the real action figures in the brain, neurons. Fields’ talk was about astrocytes – they are both one of the main problems in spinal cord regeneration (may block growth) and one of the potential solutions (may promote myelin repair). I’m not going to get into his astrocytes story. Get his book, it’s quite readable.

To me what was most notable about Fields’ contribution to W2W was his reporting for Scientific American. He picked up on a proposed clinical trial at the Miami Project to implant autologous (from patient’s body) schwann cells into acute spinal cord injuries. This sort of therapy has been talked about for more two decades and has had preclinical data in animals showing that schwann cells – if in the presence of other growth-promoting factors – can boost axons across the site of injury on the cord. In the Miami case, the schwann cells will not get any help; they are being tested alone for safety in acute SCI. Dalton Dietrich, who is Scientific Director at MP and who made the presentation, said the goal is to move to people with chronic SCI but that they can only get there as fast as the FDA allows. Read: slowly.

Neither Dietrich nor Fields mentioned that a 33-patient trial has already tested autologous schwann cells in 33 chronic humans, in Iran. A two-year follow-up found the cells to be safe. But without effect. Miami researchers have done years of work on schwann cells and know that the cells alone aren’t going do much; adding other molecules, including cAMP, chondroitinase or olfactory ensheathing cells boosts axon growth and helps restore function. Hurry up and wait: no combo trials allowed

OK, not much new there but the schwann cell story did make SA; no doubt some of its professional rectitude rubbed off on the W2W hegemony.

As for not-quite-baked speculation, Fields might have noted another pending clinical trial, again in acute SCI, for a biodegradable polymer scaffold implant. This is the InVivo Therapeutics story. Good animal data, smart guys with intellectual property and money (announced at W2W that Ed Wirth had jumped over from Geron) and with lots of swagger. Potential in chronics. SCI as an engineering problem.

Fields didn’t bite, and I guess he didn’t stick around for day two, either. Good vibes all around for chondroitinase, a cool bacterial enzyme that, in overly simple terms, eats away spinal cord injury scar. Case Western scientist Jerry Silver made a strong case for ch’ase plus nerve grafts in an animal model for both respiratory recovery and bladder recovery. But first, to set his stage, came Anthony Caggiano, VP for Preclinical Development at Acorda Therapeutics. Acorda has the patent for Ch’ase. He described how the enzyme has improved function in animal models of SCI, including results from the James Fawcett lab that I described last June.

Many labs, at least two species. News is good about ch’ase. What’s the hold up? “Why don’t we rush headlong into developing the drug? Caggiano asked. “There are several challenges.” Safe delivery is the main one – will neurosurgeons be OK with injecting the enzyme several times into the injured cord? Might there be other ways to bathe the scarred area without injection?

(Not to cheerlead for the Reeve folks but the work of both Silver and Fawcett got funding from the Reeve Foundation. So did some of the Miami Project's schwann cell work.)

Jerry Silver was clearly the W2W MVP this year. Not only was his science brilliant (see the paper from Nature) but he was charmingly direct, including comments about some information that's fed to the cure tribe. Here’s a sample, and if you don’t know who he’s talking about, I’m not going to speculate here.

 

“What I have seen is that people do these small lesions in animals and get them to do a small task better than if they hadn't got [his] special treatment after that lesion . . . and then try to extrapolate that and spread false hope about what that means for humans, you're not being completely honest. The preclinical data is not strong enough to justify the claims you're making. I have a strong feeling that we should not create false hope.”

Another:

“Importantly, there is zero published data showing that umbilical cord blood stem cells plus lithium has been effective to foster recovery in an appropriate animal model of SCI at long chronic stages. He's got a clinical trial and we don't. I am keeping my fingers crossed on this one.”