The Science of Stem Cell Therapy

Transcription

1 The Science of Stem Cell Therapy AVM Biotechnology City Centre Building 1420 Fifth Avenue, Suite 2650 Seattle, WA Copyright 2008 AVM Biotechnology, LLC

2 speaker disclosure Theresa A. Deisher, Ph.D Stanford University School of Medicine, Ph.D. in Molecular and Cellular Physiology Commercial Positions Genentech Repligen Hematopoietic Stem Cell Chemoattractants ZymoGenetics Adult Cardiac Stem Cell; Mesodermal- Derived Stem Cell; VSEL Very Small Embryonic-Like Stem Cell Immunex Amgen Derivation of Embryonic-Like Stem Cells from Human Cord Blood AVM Biotechnology President & CEO Sound Choice Pharmaceutical Institute President Over 23 Issued/Published Patents; 3 discoveries in clinical trials

3 Worldwide Stem Cell Progress (sold or tested) Alliance for Regenerative Medicine January 2013

4 Worldwide Stem Cell Progress (sold or tested) Location of Company Headquarters Ongoing Clinical Trials Europe 20% 20% United States 65% 55% Other Countries 15% 25% Alliance for Regenerative Medicine January 2013

5 FDA Approved Stem Cell Products Alliance for Regenerative Medicine January 2013

6 Approved Stem Cell Products Alliance for Regenerative Medicine January 2013

7 Open Clinical Trials US National Institutes of Health Open/Interventional/Adult Stem Cell Ph I Ph II Ph III Ph IV Total US ROW Bone Marrow Adipose Stem Cells % 12% 03 May 2013

8 Open Clinical Trials US National Institutes of Health Open/Interventional/Embryonic or Fetal Stem Cell Embryonic Fetal 6 2 Macular Degeneration Stargardt's Macular Dystrophy ALS Myasthenia Gravis 03 May 2013

9 What is a stem cell? What is a Stem Cell?

10 What is a Stem Cell? Nucleus of adult heart muscle cell Adult Stem Cell nucleus cytoplasm

11 Stem Cell Lineage Commitment Totipotent stem cell: can give rise to any adult, fetal or placental cell Pluripotent stem cell: can give rise to any type of fetal or adult cell: includes embryonic, reprogrammed, spermatogonial stem cells Multipotent stem cell: can give rise to a limited number of cells, usually confined to the cell types of one tissue

12 Pluripotent Stem Cells can Generate an Entire Mouse a True Clone In this study, mouse fetal cells were reprogrammed to be embryonic-like. Then, a single reprogrammed cell was injected into an incompetent or tetraploid embryo which can form only the placenta. Tetraploid embryos are made by fusing 2-1 celled embryos together using electricity. The reprogrammed cell injected into the tetraploid embryo became an entire mouse.

13 Proof of Pluripotency is Tumor Formation Pluripotent stem cell: can give rise to any type of fetal or adult cell: includes embryonic, reprogrammed, spermatogonial stem cells

14 Embryonic Stem Cell Trials Are they actually using embryonic stem cells? They try to differentiate the ES cells to eliminate tumor formation Embryonic stem cells (ES) Neural cells : oligodendrocytes

15 Can embryonic stem cells be made safe? Purity of cells injected is determining Purity after differentiation : Maximal 98% Manufacturing scale 85% Geron Acute Paralysis Trial example 15,000,000 differentiated ESC injected 98% purity 300,000 ES cells 85% purity 2,250,000 ES cells Minimum ES to form tumors in mice 500 Projected number to form tumors in humans 500,000

16 Can embryonic stem cells be made safe? Geron Clinical Trial example: Acute paralysis 50% recover spontaneously Would expect a benefit by odds Projected price tag <$500,000 USD Trial cancelled suddenly Nov 2011 Entire ES program cancelled also

17 Adult stem cells are found in: Bone marrow Blood Heart Brain Liver Pancreas Kidney Umbilical Cord Blood Placenta What is an Adult Stem Cell?

18 Adult Stem Cell Products Updated Saturday, January 22, 2011 at 05:53 AM

19 Veterinary Adult Stem Cell Products MediVet VetStem

20 Veterinary Stem Cell Products Why not use animal embryonic stem cells? Form tumors Trigger Immune Rejection Very expensive Veterinary applications of adult stem cells : No tumor formation safe No Immune Rejection $1,800 to $3,500 USD As effective as $12,000 surgeries

21 Human Clinical Trial Results Blindness Paralysis Type I Diabetes Stroke Heart Attack

22 Stem Cells for Chemical Burn Blindness Blindness caused by chemical burns One patient was blinded in 1948; 112 patients total treated 89% improved 76% full; 13% partial Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration N Engl J Med 2010; 363:

23 Stem Cells for Chemical Burn Blindness Improvement was permanent

24 Stem Cells for Paralysis Complete spinal injury at C6/7 No leg movement, minimal finger movement Treated 2 years after injury Can walk 30 feet with walker Can wave without help Without stem cell treatment, 5% improve With single stem cell treatment, 50% improve

25 Stem Cells for Paralysis 7 patients treated 6 months to 6.5 years after injury Several patients recovered bladder and/or bowel control

26 Stem Cells for Type I Diabetes

27 Stem Cells for Type I Diabetes 12 continuously insulin free 8 transiently insulin free

28 Survival is dramatically improved Room for further functional improvement as the Rankin score for these 16 patients declined only from 4.8 to 4.0 (normal score would be 0 to 1.0) Stem Cells for Stroke

29 Stem Cells for Heart Attack 5-year event free survival is significantly improved Room for further functional improvement Pumping capacity of the heart improved by only 5-8% Source: Leistner DM. REPAIR AMI Trial. AHA Scientific Sessions 2011 BMC = Bone marrow-derived mononuclear cells

30 Stem Cells for Stroke Treatment of ischemic stroke patient with autologous bone marrow mononuclear cells (BMC) Direct injection to middle cerebral artery (MCA) majority of stem cells migrate to the spleen Stem cell sequestration in the spleen is a general phenomenon of stem cells and has been observed in multiple diseases Source: Barbosa da Fonseca et al. Circulation 2010

31 Stem Cells for Heart Attack Stem cells injected into heart via catheter Stem cells exit from the heart and accumulate in the spleen (red - viable) and liver (yellow not viable) Scale: red highest, purple lowest Even when stem cells are applied surgically, enmeshed in a matrix or gel, they escape into the blood stream and accumulate in the spleen. <10% will remain in the heart.

32 Stem Cells are Treating Osteopetrosis Sickle cell anemia Type I Diabetes Stroke Limb Ischemia Heart Attack Heart Failure Lupus Multiple Sclerosis Spinal Cord Injury Type II Diabetes Parkinson s Bone Fractures Crohn s Sjogren s Retinitis Epilepsy Cirrhosis Nephropathy Myasthenia Gravis Lypodystrophy Cartilage Repair

33 Optimizing Adult Stem Cell Therapies AVM-SC-001 Blocks Stem Cell Sequestration in Spleen and Lymph Node 45 minutes CONTROL AVM-SC- 001

34 Preventing Stem Cell Sequestration. Optimizes effectiveness of stem cell therapies for stroke, heart disease, paralysis, etc. Allows systemic administration of stem cells: Opens possibilities for stem cells to cure: Muscular Dystrophy Cystic Fibrosis

35 Stem Cell Summary Embryonic Stem Cells Tumor forming Immunogenic Destroys a human embryo Exploits women Old technology (1980) Never helped anyone $500,000 Adult Stem Cells No tumors Self so no rejection Moral/ethical No exploitation New technology (1999) Helping people now $25,000 or less

36 Technology versus Trafficking Adult Stem Cells Clinically Characterized Patients: Different ethnicities, disease states Non-invasive: derived from blood, fat, urine Embryonic and Fetal Stem Cells Not Clinically Characterized: Very Invasive: Cells are extracted from the donor/ victim for research use. Slavery, exploitation and death.

37 What have we learned? There are many different kinds of stem cells The best stem cell for a patient is their own has limited patentability Preferred source of stem cells is the bone marrow Bone marrow cannot be patented We absolutely require government funding Patients in the United States are being deprived because our government won t fund safe, effective stem cells

38 Pluripotent Stem Cells can Generate an Entire Mouse This is called tetraploid complementation. ESC, ipsc and SSC can all give rise to a whole mouse using tetraploid complementation. Embryos are REQUIRED.