Discovery of Biomarkers as Targets for CNS Regeneration

3D illustration of single cell analysis

Despite progress in neuroscience and neurosurgery, few options exist to drive regenerative repair after spinal cord injury, or for demyelinating conditions and other neurological disorders. However, novel transcriptomic and proteomics approaches are providing insights into barriers for regeneration and offer approaches for overcoming these obstacles.

In some cases, the Neuroregeneration and Neurorehabilitation Lab has identified genes or proteins that show why some neural cells regenerate and others don't and illuminate disease stage-specific mechanisms. For example, using a liquid-chromatography tandem mass spectrometry proteomics approach — referred to as parallel reaction monitoring — the Scarisbrick team identified that reduced levels of carnosine dipeptidase 1 (CNDP1) in cerebral spinal fluid (CSF) can differentiate relapsing remitting multiple sclerosis from more progressive stages of disease. CNDP1 is an oligodendrocyte-enriched protein with antioxidant properties.

Using a degenerate polymerase chain reaction primer cloning strategy, the Scarisbrick team also identified a novel serine protease, referred to as kallikrein 6 (Klk6), for the first time. Like CNDP1, Klk6 is an oligodendrocyte-enriched protein that parallel reaction monitoring demonstrates is reduced in the CSF of people with relapsing remitting or progressive multiple sclerosis (MS). By contrast, parallel reaction monitoring showed that olfactomedin 1 (OLFM1), a glycoprotein secreted by neurons to prevent growth cone collapse, is increased in the CSF of people with progressive MS.

Ongoing studies in the Scarisbrick lab seek to identify the role these proteins play in neurological injury and disease. The lab also hopes to discover how to modulate these proteins to promote regeneration in the central nervous system.

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