Towards a stem cell based therapy for Parkinson s Disease

Transcription

1 Stem cell based therapies for Parkinson s Disease Towards a stem cell based therapy for Parkinson s Disease MALIN PARMAR NYSCF Robertson Investigator Lund University, Sweden INTR, Port Douglas, Sept 13-16, 2017 MALIN PARMAR Professor in cellular neuroscience Lund University, Sweden NYSCF Robertson Investigator

2 Stem cells in life Zygote Blastocyst Gastrula Ectoderm Mesoderm Fertilization Endoderm Stem cells creates the cells in our body during development Stem cells also replenish many of our organs throughout life Stem cells in the blood makes 1 trillion (10 12 ) new blodcells every day

3 Stem cells in regenerative medicine Stem cells can serve as reservoirs for cells and tissues needed to repair the human body Hope vs Hype

4 What is a stem cell? 1. Make more stem cells = self renewal Stem cell 2. Make more mature cells = differentiation

5 Different types of stem cells In vitro Zygote Blastocyst Gastrula Ectoderm Mesoderm Fertilization Endoderm ES cells Selfrenewal Selfrenewal Organ-specific stem cells Endoderm Mesoderm Ectoderm

6 Which diseases can be treated with stem cells? Diabetes Pluripotent stem cells Heart Disease Parkinson s Disease Pre-clinical studies Disases in the eye Retinal pathologies Clinical trials... Tissuespecific stem cells Leukemia and other diseases in the blood Routine treatments

7 Stem Cell Treatments for Neurodegenerative Disease Parkinson s Disease Huntington s Disease Alzheimer Stroke ALS Charles and John Sabine

8 Parkinson s Disease Tremor Muscle rigidity Difficulties initiating movements Posture and balance Non-motor symptoms Image from: This is Parkinson s

9 Parkinson s disease Loss of midbrain dopamine neurons Healthy PD Supply dopamine via medication

10 Transplantation of human fetal DA neuroblasts Fetal DA neurons Cell suspension Stereotaxic injection

11 An instrument guides cells to their correct location

12 The method results in significant clinical benefit Before transplantation 12 months post-op Courtesy of Dr. Ivar Mendez, Halifax transplantation program

13 Difficulties using fetal cells Large variation in outcome Lack of material Ethical and societal considerations that vary with national regulations Logistical and practical issues

14 Stem cells! Stem cells are an unlimited source from which transplantable cells can be derived

15 Not all tissue specific (adult) stem cells are the same: 95% av kroppens celler

16 new cells/day Erythrocytes Stemcell progenitorcell Lymphocytes Platelets

17 This is not the case for the brain: - Hard to get to - Low division (if any) - New neurons formed in only very limited regions of the brain - Do not self repair

18 This is not the case for the brain: - Hard to get to - Low division (if any) - New neurons formed in only very limited regions of the brain - Do not self repair

19 Embryonic stem cells are isolated from preimplantation blastocysts an early developmental stage Cleavage stage embryo Cultured blastocyst Isolated inner cell mass Cells dissociated and replated Irradiated mouse fibroblast feeder cells Blastocyst New feeder cells Established embryonic stem cell cultures

20 Embryonic stem cells are pluripotent and can make all mature cell types of the body In vitro Zygote Blastocyst ES cells Fertilization Mesoderm Endoderm Ectoderm Red blood cells Blood vessel Skeletal muscle cells Alveolar cells Epithelial cells of gut Pancreatic cells Neurons Skin cells - epidermis Pigment cells

21 Dopamine neurons derived from stem cells

22 Pre-clinical assessment in animal models of PD Rotationstest: Cylindertest:

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24 Analyze the cells after transplantation

25 Form mature DA neurons Release dopamine stem cell derived DA neurons survive and function en par with fetal DA neurons Repair Circuitry Restore motor deficits

26 A Global Effort Gforce-PD G-force PD: A Global Effort to Bring Cell Based Therapies to PD Patients

27 Conclusions and future directions Blastocyst ES cells x Fetal mesencephalon Dopaminergic neurons Patient x Stem cells in adult brain ips cells Hematopoietic and/or mesenchymal stem cells Bone marrow Skin biopsy

28 THANKS FOR LISTENING AND THANKS TO MY FANTASTIC COLLEAGUES!

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