This document summarizes stem cell research for ALS and patient perspectives. It describes the different types of stem cells (adult, embryonic, induced pluripotent), their purposes in ALS (replacing motor neurons or supporting cells), and several clinical trials testing stem cells for ALS in the US and internationally. While patients have high expectations for cures, the document cautions that progress will be slow and individualized therapies may be needed given ALS is likely a syndrome. It outlines sources of information for patients and considerations like safety for stem cell interventions.

1. Decoding Stem Cells for
ALS
ALSA
November 7, 2014
Dallas A Forshew, RN, BSN
Manager, Clinical Research
ForsheD@cpmcri.org Forbes Norris ALS Research Center
San Francisco, CA

2. Overview
 Patient perceptions
 What are stem cells?
 Where do they come
from?
 How are they
produced?
 What are they
intended to do?
 Studies
 International
 United States
 Dangers???!!!!
 The Future
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3. Wide range of ALS patient
expectations regarding Stem Cells
 Cure and quickly
 Stabilize weakness
 Regain strength
 Give hope
 Some patients have trached and vented in
anticipation of a cure from stem cells
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4. What is NOT Appreciated by Most
Patients
 ALS will continue after stem cell
administration
 Supportive cells may play a key role
 Nerves grow very slowly
 There are many kinds of neural stem cells
and these behave differently
 There are applications for use of stem
cells in drug discovery and refinement of
sub-types of ALS
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5. Case Study 1
 RT, 54 yr old male, leg onset 3 yrs ago
 Bulbar and breathing normal, just started using
motorized w/c, minimal UE weakness
 Most ALS patients are very optimistic
 Stem cells are the answer, nature will cure itself
 Wants to regain walking ability
 Too much hype from Brainstorm
 Unrealistically heightens expectations
 Understands that the Emory pt who regained strength was
a fluke
 Moved to Atlanta to have a better chance of getting stem
cells
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6. Case Study 2
 MG, 70 yr old male, onset 7 yrs ago
 No use of arms or legs, minimal bulbar
changes, some respiratory involvement
 New science that is just beginning to be understood
 Stem cell progress in ALS will come slowly
 Since ALS may be a syndrome, individualized/cocktail
therapies will be needed
 No one knows how ALS is initiated or spreads
 Stem cells can be used to develop treatments and
cures
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7. Where do Patients get Information?
 ALS Association / Muscular Dystrophy Association
 Internet, support groups, webinars
 NEALS (Northeast ALS Consortium)
 Internet, webinars, yearly workshop aimed at creating patient
research ambassadors
 ALS World Wide
 Internet, A Patient’s Path through the Stem Cell Maze
 ALS TDI (Therapy Development Institute)
 Internet, ALS 101 seminars
 Patients Like Me
 Patients talking with patients
 Google “ALS and Stem Cells”: 1,290,000 hits
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8. What are Stem Cells
 Master Cells of the body
 Can renew themselves (self-renewal)
 Can make a variety of other cells
 Two kinds
 Adult stem cells
 Embryonic stem cells
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9. Adult Stem Cells
 Stem cells in specific tissue that replenish
their particular tissues
 Bone marrow, brain, adipose tissue, liver,
skin, teeth, reproductive system
 Multipotent
 able to form multiple types of cells in their home
tissue
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10. Embryonic Stem Cells
 Origin
 Made from embryos from fertility clinics that are
no longer going to be used
 Embryos that would otherwise be discarded
 2 - 5 days old
 Pluripotent
 Can be manipulated to form any kind of cell
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11. Induced Pluripotent Stem Cells
 iPS Cells
 Share many properties with embryonic stem cells
 Model of disease
 ALS not just one disease
 Drug discovery
 Use iPS cells instead of mice
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12. A Rose is a Rose is a Rose Gertrude Stein
 But a stem cell is not a stem cell…
 Stem cells from different labs are very different
 They do not turn into the same kind of cells
 They do not behave the same
 Each time a new stem cell line is produced, the
FDA treats it as a new drug
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13. Purpose of Stem Cells in ALS
 Replace nerves??
 Motor neurons grow very slowly
 1 mm per day but…
 Replace supporting cells in spinal cord
 Astrocytes, glia cells, etc
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14. Supportive Cells
 Glia Cells
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15. Astrocytes
 Most common support cell in brain and spinal
cord
 Transport nutrients to neurons
 Help form a network on which neurons grow
 Phagocytic ability to clean CNS debris
 Help maintain correct chemical concentrations
around neurons
 Key to the growth of new neurons from neural
stem cells
Astrocyte
Image courtesy of Biodidac
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16. Other Glia Cells
 Microglia
 Phagocytic ability to clean CNS debris
 Oligodenendroglia
 Schwann cells of the CNS
 Insulation to neurons
 What makes white matter white
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17. Clinical Trials
 Clinicaltrials.gov
 21 clinical studies
 Mexico, Iran, China, South Korea, Poland, India,
Italy, Spain, France, Israel
 All types of stem cells, mostly bone marrow
 All routes of administration
 Vein, muscle, brain, spinal fluid, spinal cord
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18. Neuralstem, Inc
 US company
 Commercially produced, large quantities
 Derived from a single 8 week old aborted fetus
 Aimed at producing human neurons and glia cells
 Phase I trial completed
 Emory University, Atlanta, GA
 FDA approved implementation of Phase II trial
September 2013
 Emory University, Atlanta, GA
 University of Michigan, Ann Arbor, MI
 Mayo Clinic, Rochester, MN
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19. Neuralstem, Phase I Study
 Emory University
 Intrathecal injection of spinal-cord derived
stem cells from a single 8 week old fetus
 Phase I safety trial
 Are these stem cells safe?
 Is the route of administration safe?
 18 Surgeries in 15 patients
 Result: safe!
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20. 20
Riley, Jonathan, et al., Congress of
Neurologic Surgeons, 5/4/12

21. Neuralstem, Phase II, Open Label
 Emory, U of Mich, Mass General
 Same cells, same route
 Only local sALS patients
 15 ambulatory patients, 5 groups
 Cervical spine injections for 1st 2 groups
 Cervical and lumbar injections for last 3 groups
 Dose escalation
 Increasing number of injections and numbers of cells
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22. Brainstorm-Cell Therapeutics
NurOwn
 Hadassah Medical Organization, Israel
 Successful Phase I study in Israel
 Safe!
 Phase IIa started December 2012 in Israel
 Bone marrow derived autologous stem cells
secreting neurotrophic factors (NTF)
 Dose escalating
 12 patient (full)
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23. Brainstorm, Phase II, D-B, P-C
 Mass General, U Mass, Mayo Rochester
 Stem cells from pt’s own bone marrow,
propagated ex-vivo, induced to secrete NTFs
 IM and intrathecal one time injections
 48 pts
 By invitation only, must be local
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24. Mayo Clinic, Rochester, MN
 Phase I study
 5 groups of 5 patients, dose escalation
 20 already enrolled
 Autologous adipose tissue derived stem cells
 Adipose tissue removed via syringe through abdominal
incision
 media fed to fat cells so stem cells precipitate out
 growth factors induced (promote nerve growth and
protection)
 expanded to billions (takes several weeks)
 injected into spinal fluid
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25. Cedars Sinai, Phase I, Open Label
May include Emory and Forbes Norris
 Funded through CIRM
 (California Institute for Regenerative Medicine)
 Protocol not complete
 18 patients, early in disease, still walking
 Same surgical technique as Emory
 Lumbar spine only
 Probable start, early 2015
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26. UC San Diego
UC San Francisco
 Funded through CIRM
 Stem Cells from UCSD
 Problems in cell development causing delay
 May start in 2015
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27. Cell Surgical Network
 ~ 35 US centers
 Clinical Intervention Study
 Adverse Events and Clinical Outcomes for the Deployment
of Adipose Derived SVF (Rich in Adult Stem Cells and
Growth Factors) for Select Orthopedic, Neurologic,
Urologic, and Cardio-Pulmonary Conditions.
 Autologous adipose stem cells
 Liposuction, centrifuge to separate stem cells from
fat, add to IV fluid, infuse peripheral vein or injected
directly into joints, subcutaneously, into spinal fluid,
or nebulized
 Not FDA approved
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28. ALS Therapy Development Institute
 Collecting blood, skin and medical history
 Purpose
 Sequence genome of each patient
 Create and bank induced pluripotent cell lines
 Use iPS cell lines to search for mechanisms of disease
 And screen for potential teatments
 Collection at MGH Derm Dept, Boston
 http://www.als.net/ips/prescreen/?f=hr
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29. Caution!!!
 Things can go wrong!
 Stem cells are manipulated to reproduce
 Cancer is a risk
 Route of administration
 Surgery, anesthesia
 Immunosuppression
 Infection
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30. Summary
 Hopeful
 Not quite ready for prime-time
 Change thinking from replacement to
restorative, repair, protect
 Resources
 Clinicaltrials.gov
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