Enabling Stem Cell Research in California

Gil Sambrano, Ph.D.

California Institute for Regenerative Medicine

What is a stem cell?

1. Mature/specialize

2. Self-renew

Stem Cell Capacity

Stem Cell Capacity

Human embryonic stem cell lines were first derived in 1998 by Dr. James Thompson.

Embryonic Stem Cellsvia In Vitro Fertilization

Potential of Stem Cell Research

• Tissue/cell replacement

• Gene therapy/drug delivery

• Models of disease in vitro

• Drug screening and drug development

• Basic knowledge of human development

An enabling technology for:

A path to new therapies and cures for many diseases

Somatic Cell Nuclear Transfer

Scale of a Human Egg

2001 Presidential Executive Order for Embryonic Human Stem Cell Research

• Prohibits use of Federal funds on embryonic stem cell lines derived prior to August 9, 2001

• Lines must have been derived from unused embryos that were made for IVF

States Respond

• California: California Institute of Regenerative Medicine

• Connecticut: Connecticut Stem Cell Research Grant Project

• Illinois: Illinois Regenerative Medicine Institute • Maryland: Maryland Stem Cell Commission• Massachusetts: Governor's Life Science Initiative• Minnesota: Stem Cell Institute• New Jersey: Stem Cell Institute of New Jersey• New York: Empire State Stem Cell Trust Fund• Ohio: Center for Stem Cell and Regenerative

Medicine

Proposition 71• Approved by 59% of CA voters

• Authorized $3 billion to fund stem cell research in CA

• Affirmed the right to conduct research not supported by federal funding

• Banned reproductive cloning

• Required development of medical and ethical standards

• Independent Citizens Oversight Committee (ICOC): 29 members

– Chair: Robert Klein– Vice-Chair: Ed Penhoet, Ph.D

• California Institute for Regenerative Medicine (CIRM): 50 member staff (currently 26)

– President: Alan Trounson, Ph.D.

Mission Statement

To support and advance stem cell research and regenerative medicine under the highest ethical and medical standards for the discovery and development of cures, therapies, diagnostics and research technologies to relieve human suffering from chronic disease and injury.

“Turning stem cells into cures.”Roman Reed

Working Groups of the CIRM

• Standards and Ethics Working Group (19)– (prominent ethicists, scientists, patient advocates)

• Grants Review Working Group (23)– (distinguished scientists from outside California, patient

advocates)

• Facilities Working Group (11)– (real estate experts; patient advocates)

Building a State Agency

and a Funding Agency

ProceduresRegulations

Grants managementComplianceTracking

Legal ChallengesFor over two years legal challenges prevented the institute from issuing bonds

• Two consolidated lawsuits challenged our constitutional authority to spend state money– Very strong decision in Superior Court in May 2006 upholding

CIRM position; appealed– In May 2007, the California Supreme Court declined to hear

appeal and ended the legal challenge

• A third lawsuit (dismissed) asserted that we are depriving frozen embryos of their constitutional rights

Funds for a Funding Agency

Bond Anticipation Notes (BANs)-Authorized $14 M in BANs in April, 2006 for first year of training grants;

-Additional $36 M in BANs for research grants.

Governor’s Loan$150M loan provided to CIRM by Governor Schwarzenegger in July, following Presidential veto on Castle-DeGette bill

Making a plan

Scientific Strategic Plan

• Define long-term objectives that CIRM will pursue over ten years

• Involved interviews with scientists, clinicians, ethicists, patient advocates, public interest groups

• Focus group discussions and public meetings

• Heard from ~200 individuals

• A “living plan” with mechanisms for review and modification

Published December 2006

Strategic Planning Framework

Laying the Foundation Preparing for the Clinic Clinical Research

Scientific Training & Development

Innovation Science

Mission-Oriented Science

Tools, Technologies &

Infrastructure

Facilities

Communities of Science

Responsibility to the Public

Funding

Initiatives

Res

ou

rces

Strategic Plan Goals

• Aspirational Goals:– What we hope to achieve– Use stem cells to cure disease– California as world-wide leader in stem cell

research

• Commitment Goals:– Our covenant with the people of California for what

we will achieve over the next ten years

Commitment Goals: Context

• Scientifically young field

• Therapeutic drug development: takes time and fails more often than it succeeds

• New treatment modality: cellular therapy

Commitment Goals

• Focused on human embryonic stem cells, with emphasis on cell replacement therapy

• Ten year goals– Goal 1: Clinical proof of principle that transplanted cells derived

from pluripotent cells can be used to restore function for at least one disease.

– Goal 2: Therapies based on stem cell research in Phase I or Phase II clinical trials for 2-4 additional diseases

Laying the Foundation

CIRM Training Program

• 16 non-profit institutions in California• 169 Trainees (pre-doc, post-doc, clinical)• Course in stem cell biology• Course in ethical, legal, and social issues• Annual meeting of trainees

• Grants awarded in April, 2006• Total ~$38M for 3 years

“Jumpstart” Initiative to Enable Stem Cell Research

• CIRM SEED Grants– $200K/yr, 2 yrs– Innovative projects

• Comprehensive Research Grants– $400K/yr, 4 yrs– Established investigators in SCB/related field

• Shared Laboratory Space– Fund renovation of lab space for hESC work– Fund instructional course

Latest Initiatives

• New Faculty Awards– Enable young faculty scientists and

physicians to

• New Cell Lines Awards– Enable the development of new pluripotent

stem cell lines for research and therapies

• Disease Teams– Create teams of researchers

What’s Next

• New President

• New Initiatives

• Develop for-profit funding

• Community outreach

• Growing the Institute

Acknowledgements

• Bob Klein• Zach Hall• Arlene Chiu• Alan Trounson• Rich Murphy• CIRM Team

• All those who have generously contributed their time and expertise to making CIRM and the vision embodied in Proposition 71 a reality

Scientific Challenges

• Capabilities of different types of stem cells

• Control division in vitro and in vivo

• Control paths of differentiation

• Safe production of large numbers of cells

• Immunological tolerance

• Production of SC lines with disease phenotypes