Assoc Prof Bronwen Connor 23 March 2013

A/Prof Bronwen Connor Neural Repair and Neurogenesis Lab Dept of Pharmacology & Clinical Pharmacology Centre for Brain Research University of Auckland Overview  What is a stem cell?  Discovery - our research  Adult stem cells  Reprogramming  Stem cells in the clinic  the Myths  the Reality What Is A Stem Cell?  Unspecialised cells  Unique ability to grow into many different cell types in the body  Involved in development (embryonic stem cells)  Also found in many adult tissues and serve as an internal repair system (adult stem cells) What is Unique About Stem Cells?  Capable of dividing and renewing themselves for long periods  Can be directed to turn into specialised cells What is So Exciting About Stem Cells?  New potentials for treating many neurological diseases and injuries  Provide new replacement cells  Provide supporting chemicals - enhance axon growth - prevent cell death - prevent inflammation  Information about how brain cells develop and are affected by disease process What Are Embryonic Stem Cells? What Are Adult Stem Cells?  Uncommitted cells found in adult tissue or organs  Can self-renew and generate the specialised cells found in mature tissue / organ  Involved in maintenance and repair  Exciting use in cell replacement therapy as provides potential to use patients own stem cells! Sources of Adult Stem Cells Neural stem cells New brain cells Mesenchymal stem cells Bone, cartilage, fat, connective tissue Neural crest stem cells Bone, cartilage, fat, connective tissue, brain cells Hematopoietic stem cells Blood cells Similarities and Differences Between Embryonic and Adult Stem Cells  Embryonic stem cells can become any cell type (pluripotent) - but can form tumours  Adult stem cells limited to become cells from tissue of origin - unlikely to form tumours  Adult stem cells rare and more difficult to grow in lab  Embryonic stem cells grow easily but ethical issues regarding source  Adult stem cells can obtained from patient - Removes issues of rejection A bit of “Science Fiction”  Skin cells can be turned into embryonic stem cells!! Skin Cells 2012 Nobel Prize Winner We Can Turn Skin Cells Into Immature Brain Cells !!! SOX2/PAX6 Skin cells Maucksch et al 2012 JSRM We Can Take Patients Cells and Turn Them Into Specific Brain Cells  Dopamine neurons made from skin cells taken from Parkinson’s disease patient The Myths and Reality “It’s nothing that a few stem cells and 75 years of research can’t fix” The Truth - Current Clinical Trials  Clinical trials are used to establish whether new treatments are safe and effective  Unwanted side effect?  Risk level?  Benefit level?  Clinical trials are based on extensive preclinical research and rigorous peer review  Stem cell therapy MUST obtain US FDA (or equivalent) approval The Truth - Current Clinical Trials  Bone marrow / umbilical cord stem cells  Undergoing clinical trials for a range of disorders ○ Heart disease; vascular repair; bone and cartilage repair etc  Clinical trials in CNS: ○ Multiple sclerosis; motorneuron disease; stroke; cerebral palsy etc  Autologus; easily accessed; currently approved for leukemias and rare blood disorders  No evidence bone marrow / umbilical cord stem cells generate new brain cells  Provide chemicals to protect cells, support re-growth of connections, stimulate resident stem cells, reduce inflammation Approved Clinical Trials – Neural Stem Cells Company Cell Type Development Progress Indication Indication ReNeuron ReN001 (adult neural stem cells 12 wk old fetus) Commited, not pluripotent Phase Ischemic stroke Six months to two years after injury StemCells HuCNS-SC (adult stem cells derived from fetal tissue) Cultured but not altered Same cells used for both Batten’s and cord injury Phase Chronic spinal cord injury Batten’s disease Neuralstem NSI-566RSC, human spinal cord–derived neural stem cell lines Phase Amyotrophic lateral sclerosis IND filed Chronic spinal cord injury Geron GRNOPC1 (oligodendrocyte progenitor cells, derived and differentiated from hESCs) Phase HALTED! Spinal cord injury (acute—7 to 14 days after injury) The Myths – Stem Cell “Clinics”  Multiple diseases treated with the same cells  Claims based on patient testimonials  Clinical trials are based on extensive preclinical research or Phase 1/2 clinical trial data  The source of the cells or how the treatment will be done is not clearly documented  Claims there is no risk The Myths – Stem Cell “Clinics”  High cost of treatment or hidden costs  It is not customary for someone to pay to be in a clinical trial Consider whether you should pay for a treatment that is unproven  Ask about the costs of emergency medical care if something goes wrong, particularly if you are outside your own country  No follow-up after procedure  No assessment of improvement No reporting of the outcomes of the procedure to the international community The Myths – Stem Cell “Pills”  “Stimulating the release of adult stem cells from bone marrow into the circulation to slow aging process and repair areas of the body suffering from degeneration / injury.”  ColoStem  Colostrum product  Colostrum has no effect on bone marrow stem cell release The Myths – Stem Cell “Pills”  StemEnhance®  Blend of two compounds extracted from the aquatic botanical Aphanizomenon flos-aquae (AFA)  No scientific evidence that AFA effects bone marrow stem cell release or migration  Suggestions that chronic ingestion of AFA may cause liver toxicity  These are food supplements so not require FDA approval – be careful! In Conclusion  Stem cell therapy for neurological disease and injury is an exciting possibility  We still have much to learn about stem cells  We need to be sure of the long-term safety and effectiveness of stem cell therapies before clinical use  Approved clinical trials are the only way to this  Stem cell “clinics” not assist with further development of stem cell therapy and many offer empty promises  There is no “over-the-counter” stem cell “pill” Thanks To All Those Involved             Palingu Aponso Kevin Chen Jane Evans Renee Gordon Erin Firmin Rebecca Henry Kathryn Jones Adrian Kells Monica Kam Joan Lim Andrew Tattersfield Elena Vazey  Stephanie Hughes Alisa McGregor Christof Maucksch    Richard Faull Mike Dragunow Maurice Curtis    Martin Pera (USC) Mirella Dottori (Uni Melb) Malcolm Horne (HFI, Uni Melb)   Supporting Information  http://stemcells.nih.gov/info/basics  www.isscr.org  Patient guideline to stem cell therapy  www.clinicaltrials.gov/ct2/info/resources/  Please feel free to contact the Centre for Brain Research for support and information