Dr Mark Kotter

Clinical / Translation The translational focus of my group is promoting regeneration in the context of spinal cord injury. We are especially interested in Degenerative Cervical Myelopathy (DCM), a common form of compressive injury (www.myelopathy.org). We investigate the pathophysiology of DCM using reductionist and preclinical models. Based on our findings, we have received NIHR funding to conduct the first regenerative medicine trial in DCM, RECEDE Myelopathy, investigating whether a pharmacological enhancing remyelination and axonal sprouting is able to improve functional outcome after surgery. Our work expands to the development of biomarkers (including digital), understanding disease symptomology and patient stratification, as well as patient management and surgery (NIHR HTA Polyfix Myelopathy Trial). I am also the Chief Investigator of RECODE-DCM, an international multi-stakeholder consensus involving 429 individuals from 68 countries and 17 specialties, who together defined NIHR-JLA research priorities, core outcome and data sets, and a naming convention for DCM. A particular focus is the development of novel cell therapies based on a reprogramming technology developed in our lab (now the scientific basis for three start- and scale ups). Cellular Reprogramming, Disease Modelling¬ I am interested in the biology of adult CNS stem and precursor cells. We use cellular re-programming techniques to gain insight in the transcriptional and epigenetic events that determine cellular identity. We recently developed a technology for deterministic reprogramming of iPSCs into various cell types. Our aims are to 1. study basic mechanisms controlling cellular identity, 2. develop cellular platforms that can be used for studying the biology of specific human cell types, 3. create patient specific disease models for the study of genetic factors in clinical disease as well as ageing. 4. Of particular interest is the role of glia in complex CNS during homeostasis, disease, and repair and preserving and promoting axonal connectivity in cervical myelopathy, a form of spinal cord injury. Regenerative Medicine and Cell Therapy Development Our opti-ox cell reprogramming approach enables deterministic conversion of iPSCs into a wide range of somatic cell types (so far >15 protocols developed by us and other groups around the globe). The approach has proven to address the main bottlenecks of stem cell differentiation and enable unprecedented consistency (<0.1% differentially regulated genes between batches), and scale (no change in efficiency / viability from T25-T225 and beyond to 50L 3D tanks). We will conduct the first regenerative medicine trial with an opti-ox-reprogrammed cell in 2025 with further CTAs/INDs expected in 2026. The technology has been further validated by a license and collaboration agreement with Bayer / BlueRock Therapeutics, the leading big pharma company in the iPSC space.