The enzyme chondroitinase
degrades the complex sugar-chains that form scar tissue after nerve trauma. The substance is often mentioned in science articles related to spinal cord injury. Indeed, ‘chase,’ as it is called, was a major factor in the big regenerative story
this week from the Jerry Silver lab showing a strong regenerative response and bladder recovery in animals.
Here’s another publication that came out this week, from the James Fawcett lab in Cambridge in the UK, featuring chase in combination with another substance, the anti-Nogo molecule, developed by the Martin Schwab lab in Zurich. Both scientists are members of the Reeve Foundation International Research Consortium on Spinal Cord Injury, a combine of seven big labs that collaborate on projects and share their knowledge and resources.
The new paper (partly funded by Reeve) is called “Combination treatment with anti-Nogo-A and chondroitinase ABC is more effective than single treatments at enhancing functional recovery after spinal cord injury.
” Fawcett is the PI (principal investigator) and the first author is Rong Rong Zhao, a former Consortium Associate in his lab. Associates are early-career scientists (grad students or post docs) who are the main intermediaries between the Consortium labs. Also on this paper were Melissa R. Andrews, Difei Wang, Philippa Warren, Miriam Gullo, Lisa Schnell, and Schwab. Andrews, also a former Fawcett Associate, recently set up her own lab in Scotland.
Here’s the gist of the paper: While it’s been shown that chase and anti-Nogo affect recovery after SCI, the compounds do this in very different ways. Anti-Nogo is applied acutely and helps clear some of the myelin-related inhibitory substances in the damaged area of the spinal cord; clinical trials have been undertaken in Europe to assess its safety profile. Chase, meanwhile, appears to free axons from the scar barrier. Chase apparently works better if it’s given later; earlier studies showed minimal recovery when chase and anti-Nogo were applied simultaneously.
From the paper:
Anti-Nogo-A antibody and chondroitinase ABC (ChABC) enzyme are two promising treatments that promote functional recovery after spinal cord injury (SCI). Treatment with them has encouraged axon regeneration, sprouting and functional recovery in a variety of spinal cord and central nervous system injury models. … there have been no investigations on whether their effects might be combinatorial. We therefore explored the efficacy of a combination of anti-Nogo-A and ChABC as an SCI treatment.
The group used a C4 lesion model (forceps compression for 20 seconds). Anti-Nogo was applied immediately, and continuously, for the next two weeks, by way of an implanted intrathecal pump.
Three weeks later the rats had another operation to introduce chase; this included a laminectomy (opening the backbone to expose the cord). Two injections were made at C3 and C5, on either side of the lesion, of either chase or a control enzyme, penincillinase. At this time, the surgeons also inserted a cannula at the base of the skull to allow subsequent infusions of the enzymes. The animals got five more injections over the next ten days.
Another key to the study, besides the drugs, is that at four weeks post-injury all animals underwent rehab and training – the rats had already been trained, before injury, to grasp food pellets on a device that features degrees of difficulty in getting the food. Skilled paw reaching is related to recovery of cortico-spinal nerves, an important target in regenerative strategies. The animals also got a workout on ladder walking.
After treatment, the animals were measured for grasp strength, ladder climbing and for gait (paws were painted, steps were marked and analyzed). The scientists also took a very close look at the spinal cord anatomy. There was a lot of plasticity after the drugs were applied – nerve sprouting and some axon regeneration.
The verdict? From the paper:
In this study, we have shown that a combination of anti-Nogo-A and ChABC treatment, together with multi-task rehabilitation, is more efficient than either single treatment in promoting axonal plasticity and functional recovery….
We conclude that a combination of anti-Nogo-A and ChABC therapy and rehabilitation is a potentially useful treatment for SCI, provided that attention is paid to the timing of the three components of the therapy. The combination treatment produced clearly greater regeneration, sprouting and behavioral recovery than either treatment alone.