1. Anna Williams Scottish Senior Research Fellow and Honorary Consultant Neurologist MS and Update on research

2. Scottish Centre for Regenerative Medicine

3. Project Base - Edinburgh No 9, Bioincubator MRC Scottish Centre for Regenerative Medicine 230 Researchers Queen’s Medical Research Institute 650 Researchers Drug Discovery Core Clinical Research Imaging Centre Royal Infirmary 870 beds Medical School 250 Researchers Anne Rowling Regenerative Neurology Clinic – 1700 MS patients. 1/500 in Scotland Clinical Research Facility MHRA Accredited Phase 1 Unit MRC hub for Stem cell niche - £5.6 million 3

5. What causes MS? Young 1 in 500 in Scotland 2F:1M GeneticsFamily - 5%, Twin studies – 30% MZ Mac/Mc Genes – HLA DR2, IL7R,IL2R+ Immune/autoimmune – HLA DR2, periventricular plaques LatitudeGuernsey 87/10 5 population Orkney287/10 5 population Vitamin D Post-infective EBV, chlamydia, coxsackie, canine distemper virus, HHV6 Radon/ organophosphates/ whiplash/mercury fillings etc

6. Oligodendrocyte precursor cells to remyelinate Neural protection Immune attack What is MS?

7. There is an unmet need in MS therapy Anti-inflammatory drugs Neuroprotective therapies Inflammationneurodegeneration Relapses Progression disability time βIFN, Fingolimod, Natalizumab Teriflunomide, Fumarate, Alemtuzumab 7

8. Demyelination Axon degeneration Remyelination (inefficient) Neuroprotective strategies Promote axon survival as in MND, AD, stroke etc. 8

9. stem cell SELF-RENEWAL (copying) specialised cell e.g. muscle cell, nerve cell DIFFERENTIATION (specialising) grow repair renew A stem cell can self-renew or differentiate

10. Throughout life Cell from the body Genetically reprogrammed Pluripotent cell Add varying factors to differentiate into any cell type Embryonic stem cells Tissue stem cells Embryonic stem cells Induced pluripotent stem cells Add varying factors to differentiate into any cell type Liver stem cells make liver cells Brain stem cells make brain cells etc Different types of stem cells

11. What is a stem cell? Mesenchymal stem cell Pluripotent (embryonic) stem cell Neural stem cell Gut stem cell Bone Blood stem cell Cardiac stem cell Nerve Oligodendrocyte Skin stem cell Fat Cartilage ? Immune cell Induced pluripotent stem cell Skin cell

12. Recruitment Maturation DemyelinationRemyelination OPC (Tissue stem cell) What is required for remyelination? Anti- Lingo 1 abs RXRg ~10 other targets in rodent Chemorepellent Sema3A and its receptor neuropilin 1

13. Stem cell transplant problems Multiple lesions New lesions Some lesions repair themselves How do we get stem cells in? Can they migrate? Where do we get them from? How will they know what connections to make? Danger – operations, drugs, infection, tumours

14. How do we get stem cells in? One lesion No new lesions Very little repair Can they migrate? Where do we get them from? How will they know what connections to make? Danger – operations, drugs, infection, tumours Spinal cord injury – better bet

15. STEM CELLS FOR HOPE Stem cell tourism Put ‘stem cell’ and ‘MS’ into Google – get almost 13 million hits

16. Researchers Highlight Warning Signs On Adult Stem Cell Treatments Stem Cell Fraud: A 60 Minutes investigation ‘Stem cell tourism’ growing trend Panel decries overseas clinics that provide treatments devoid of scientific validity Stem cell hype and the dangers of stem cell “tourism” Stem cells in Texas: Cowboy culture STEM CELL TOURISM: SEEKING TREATMENT ON THE INTERNET AND PAYING FOR IT WITH YOUR LIFE Desperate patients warned to avoid stem cell tourism abroad over unproven 'miracle' claims Counter culture