Transcript Stem cell therapy - Irish Heart Foundation

Stem cells and gene therapy to repair the
damaged heart: will it work and is it
right?
John Martin
Professor of Cardiovascular Medicine
University College London
Small molecules
Industry funded
Heavily regulated
Mechanisms understood
Extensive toxicology performed
Intellectual property obvious
Industry total control
Gene therapy
Venture capital funded
Heavily regulated
Mechanism understood
Very extensive toxicology
Intellectual property less obvious but
possible
Control shared - biotech/academia
Stem cell therapy
Difficult to fund
Less regulated
Mechanisms not understood
Little toxicology
Intellectual property difficult
Academia can control
Gene therapy trials failed
1. because of lack of understanding
of basic biological problems
2. lack of safety
3. and small, uncontrolled trials
Collar; Pig
TRINAM:
EMEA orphan
drug status
FDA orphan
drug status and
fast track status
October 2005
Patient Safety and
Dose Escalation study
Low dose
successfully completed
Ark Therapeutics
Gene Therapy
Problems
Solution
1. Gene can disseminate 1. Local gene
to whole body
therapy
2. Can we get enough
where we want it?
2. Use a reservoir
Embryonic
The whole body
stem cells
Bone marrow
Specialised tissue
stem cells
(e.g. heart, blood vessels)
Repair of the organ
Resident
stem cells
(e.g. in heart, repairs heart)
•
Use of autologous cells in large randomised
control trials in patients with:
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Acute myocardial infarction
Late presentation myocardial infarction
Heart failure (both ischaemic and dilated)
Use of autologous cells in small clinical
mechanistic studies
Studies to test use of cytokines
Stem Cell Research Plan at Barts and UCL
3 protocols approved by ethics committee
Ischaemic
Heart Failure
Dilated
Cardiomyopathy
Acute
myocardial
infarction
(Total recruitment of 700 patients)
Gene transfer to stem cell
Thrombopoiesis of
haematopoietic progenitors
Multipotent
progenitor cell
Committed
MK-progenitor cell
Immature MK
Platelet-shedding
mature MKs
GENE
TRANSFER
(green protein)
Expression of introduced
gene in cells originated
from stem cells