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

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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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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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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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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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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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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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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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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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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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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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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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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Supportive Cells

Glia Cells

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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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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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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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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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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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Riley, Jonathan, et al., Congress of

Neurologic Surgeons, 5/4/12

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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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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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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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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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Cedars Sinai, Phase I, Open LabelMay 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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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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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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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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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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Summary

Hopeful

Not quite ready for prime-time

Change thinking from replacement to

restorative, repair, protect

Resources

Clinicaltrials.gov

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