Stem cell
therapies - treatments that involve the transplantation of stem cells, organs,
or other cells into patients to improve the function of diseased or damaged
tissues or organs - is a field that has been steadily advancing.
Perhaps more than any other industry, stem cell therapies is poised to
make a significant near-term impact on worldwide public health, and many
individuals living today may experience stem cell-related therapies.
The most obvious use of stem cells is in cell-replacement therapies,
but they are also valuable in disease modeling, drug discovery, and drug
toxicity assessment. Stem cell therapies are currently being applied to over 50
diseases including heart, lung, neurodegenerative, and eye disease, cancer, and
HIV. Part of the reason for the successful progress in stem cell therapies is
the longstanding multi-disciplinary integration of policy, science, industry,
and patient advocacy.
Public health and
drug development model is broken
Stem cell therapies could arrive just in time to help as new models for
health care delivery are sorely needed. Care delivery costs continue to rise, worldwide
populations are aging, and physician shortages are expected. The cost to bring
a new drug to market has soared to $1.3 billion, [1] and there are fewer drugs
seeking approval (in 2011, the U.S. FDA had only 23 new drugs applications as
compared with 45 in 1996). [2] Also, new classes of drugs such as cellular and
gene therapies will be even more costly and complicated than today’s already
expensive small molecule drugs and biologics. Investors have been shrinking
from the market, and at the national public health level, there could be a
bleak period of care rationing.
Stem cell therapies could find a nice fit within public health
landscapes to ease costs and provide effective disease treatment. Even if a few
of the 50 therapies currently in development were to be successful, the impact
could be substantial in both improving patient outcomes and reducing health
care costs. On the other hand, current challenges with stem cell therapies will
need to be overcome. The field is nascent with expensive therapies that are
challenging to commercialize, for example $93,000 for prostate cancer therapy
Provenge. Translation is slow, with few eligible patients actually receiving
stem cell therapies, and widespread clinical implementation could be 10-20
years away.
Contemporary stem
cell policy issues
There are three main areas of current policy concern in stem cell
therapies: the use of embryonic stem cells (ESCs), operational issues in the
manufacture of therapies, and medical tourism. Regarding ESCs, while a regulatory
ban was lifted in 2009 in the U.S. which previously limited the ESC lines that
could be used in federally-funded research, debate about the use of embryos
continues. Approximately 48,000 in vitro fertilization babies are born each
year in the U.S. [3] In the process, typically 10 blastocysts are created, only
one of which is implanted into the prospective mother. The rest are frozen,
discarded, or donated to research. Ethical debate about the appropriate use of
the unused blastocysts remains unresolved although not limited legally. There
are however solutions on the horizon. The regulatory period forced scientists
to develop other methods of generating stem cells and much progress has been
made in induced pluripotent stem cells (iPSCs), reprograming regular cells such
as skin cells back to a pluripotent stage where they can then be differentiated
into any cell type.
There continue to be exciting developments in iPSCs and an important
current focus is the direct reprogramming of one cell lineage to another
without having to induce pluripotency. Two recent efforts in this area were the
transformation of adult skin cells directly into functional neurons, [4] and
the targeted genetic engineering of human pluripotent cells with nuclease
enzymes. [5]
A second set of policy concerns operational issues. Understandably,
there is a need for manufacturing standards as the industry scales up in the
production of stem cell therapies, particularly with regard to iPSC-derived
products. [6] Consistent output, quality control, process reproducibility, and
safety testing, within clinical time constraints, are some of the points
outlined for regulation. Other cellular therapy-related policy concerns include
the issue that therapies may not fit into the current FDA approval phases and
may require alternative processes (e.g.; testing Phase I and II safety and
efficacy together), and that current loopholes by which physicians administer
drugs to patients (e.g.; access to investigational programs and off-label
prescribing) may not be appropriate for cellular therapies. [7]
The third contemporary policy issue is medical tourism which has
considerable discussion and opinion both in the popular press and from
scientists. While scientifically-rigorous stem cell therapies are slowly
progressing through regulatory approval, numerous companies in the U.S. and
abroad have begun to offer stem cell therapies which many scientists denounce
as unproven. Responses range from the outright dismissal of such treatments as
quackery and 21st century snake oil to wondering how a better job can be done
to deliver effective therapies through the traditional public health system.
The issue is compounded by some recent high-profile individuals
obtaining overseas stem cell treatments that apparently did not work, for
example those received by professional football player Payton Manning [8] and
Texas governor Rick Perry. [9] There is a call for the stronger international
regulation of stem cell therapies with an emphasis on establishing
accountability and efficacy, and the suggestion that other countries adopt
regulatory frameworks similar to those used in the U.S. and the U.K. [10]
One resource for information about clinics outside of the U.S. is the
International Society for Stem Cell Research (www.ISSCR.org). Although at
present few Americans are traveling for medical tourism (mainly orthopedic,
cardiac, and cosmetic procedures), [11]
demand could increase and it may be difficult for laypersons to assess
treatment appropriateness and efficacy.
Commercial
progress of stem cell therapies and cellular therapies
Dozens of companies are developing a variety of therapeutic solutions
using stem cells, assiduously working through clinical trials and regulatory
approval processes. The early-stage industry has been advancing quickly since
the U.S. ESC ban was lifted, and is starting to attract interest from Big
Pharma in both developing therapies in-house and acquiring startups. Some of
the most interesting studies with the potential for near-term high-impact results
are discussed below.
Neural stem cell lumbar transplantation for neurodegenerative disease -
Stem cells may be able to aid in disease conditions which do not have effective
current treatments, particularly neurodegenerative disease which has a paucity
of clinical therapies for conditions such as Parkinson’s disease, Alzheimer’s
disease, Huntington’s disease, and amyotrophic lateral sclerosis (ALS). In the
case of ALS, the best drug, Riluzole, is only estimated to extend life 3-4
months, and does not change the progression of the disease, generally 3-5 years
to death after diagnosis, as motor neuron capability is lost.
A potential solution for ALS is underway in clinical trials with
Neuralstem (Rockville MD). Positive Phase I safety data for the company’s
neural stem cell lumbar transplantation trials was presented on the first 12
patients in September 2011. [12] The trial began in January 2010.
Mesenchymal or bone marrow stromal stem cells (MSCs) for heart, lung,
and islet cell repair - Prochymal, an MSC product from Osiris Therapeutics
(Columbia MD) is in FDA Phase III clinical trials for the treatment of acute
graft versus host disease (GvHD), Crohn’s disease, and in Phase II clinical
trials for acute myocardial infarction (repair of heart tissue), diabetes
(protection of pancreatic islet cells), and pulmonary disease (repair of lung
tissue). Another product, Chondrogen, is being developed for treating
osteoarthritis of the knee.
These solutions are based on research work finding that pericytes
(connective tissue cell occurring around small blood vessels) may behave as
stem cells throughout the body [13] and harnessing the capabilities of MSCs in
secreting bioactive molecules such as growth factors, cytokines and chemokines.
[14]
Cellular
immunotherapy treatment for prostate cancer - For the treatment of
certain kinds of prostate cancer, Provenge from Dendreon (Seattle WA) was
approved in April 2010. It is an autologous (derived from the same individual’s
body) cellular immunotherapy. [15] Provenge introduces a protein to a patient’s
own immune cells that acts as an antigen for prostate cancer, which causes the
body to activate an immune response against the cancer cells. The company
estimated having the capacity to treat 2,000 patients in the first year and
opened a third U.S. manufacturing facility in August 2011.
Dermal substitutes -
Two of the most-widely used cellular therapies are dermal substitutes:
Dermagraft from Advanced BioHealing (Westport CT), and Apligraf from
Organogenesis (Canton MA), where an epidermis is formed in a 20-day manufacturing
process. Apligraf is the first allogeneic (e.g.; developed with one person’s
cells for transfer to another person, using cell types that do not elicit
immune response) cell-based product approved by the FDA and has had over
250,000 patient applications.
Cell therapy for
wrinkles - LaViv (azficel-T) is a therapy from Fibrocell Science (Exton PA)
approved in June 2011. Collagen-producing fibroblasts are biopsied from behind
the ear and cultured for 90 days, then injected into smile line wrinkles around
the nose and mouth. [16] Apparently, the treatment is longer-lasting than the
absorbable fillers used by competitors.
Spinal cord injury -
Geron (Menlo Park CA) has the first-ever embryonic stem cell clinical trials
underway for spinal cord injury with two enrolled patients as of June 2011 [17]
to investigate the use of hESC-derived oligodendrocyte progenitor cells,
GRNOPC1, in the treatment of paralysis. [18]
HIV cure -
HIV is an example where anti-HIV drugs suppress the virus but do not cure
patients. It has been discovered that individuals with a certain genetic
mutation, homozygous for the CCR5delta32 allele, are virtually resistant.
Sangamo BioSciences (Richmond CA) helped to design zinc finger nucleases that
knock out the CCR5-receptor gene and generate CCR5-negative immune cells that
would be permanently protected against HIV. The stem cells were then
transplanted successfully into the “Berlin patient” who was declared to be
cured of HIV after remaining off retroviral therapy for over three years. [19]
[20]
Melanie Swan
Ethical Technology
NOTES
[1] Gavura S. What does a new drug cost? Science-based Medicine. April
14, 2011. Available at:
http://www.sciencebasedmedicine.org/index.php/what-does-a-new-drug-cost.
Accessed: March 6, 2012.
[2] Hsu, J. Fear of Risk Threatens Medical Innovation. Innovation News
Daily June 29, 2011. Available at:
http://www.innovationnewsdaily.com/medical-innovation-pharmaceutical-drugs-2090.
Accessed: March 6, 2012.
[3] BabyCenter Medical Advisory Board. Fertility treatment: In vitro
fertilization (IVF). Online text from BabyCenter. 2011. Available at:
http://www.babycenter.com/0_fertility-treatment-in-vitro-fertilization-ivf_4094.bc.
Accessed: March 6, 2012.
[4] Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S, Lipton SA,
Ding S. Direct reprogramming of adult human fibroblasts to functional neurons
under defined conditions. Cell Stem Cell. 2011 Aug 5;9(2):113-8.
[5] Hockemeyer D, Wang H, Kiani S, Lai CS, Gao Q, Cassady JP, Cost GJ,
Zhang L, Santiago Y, Miller JC, Zeitler B, Cherone JM, Meng X, Hinkley SJ,
Rebar EJ, Gregory PD, Urnov FD, Jaenisch R. Genetic engineering of human
pluripotent cells using TALE nucleases. Nat Biotechnol. 2011 Jul 7;29(8):731-4.
[6] Carpenter MK, Couture LA. Regulatory considerations for the
development of autologous induced pluripotent stem cell therapies. Regen Med.
2010 Jul;5(4):569-79.
[7] Hyun I. Allowing innovative stem cell-based therapies outside of
clinical trials: ethical and policy challenges. J Law Med Ethics. 2010 Summer;38(2):277-85.
[8] Childs, D. Peyton Manning’s Stem Cell Hail Mary. ABC News.
September 12, 2011. Available at:
http://abcnews.go.com/blogs/health/2011/09/19/peyton-mannings-stem-cell-hail-mary.
Accessed: March 6, 2012.
[9] Brown, E. Rick Perry’s stem cell surgery worries some doctors. Los
Angeles Times. August 19, 2011. Available at:
http://articles.latimes.com/2011/aug/19/news/la-heb-rick-perry-stem-cell-back-surgery-20110819.
Accessed: March 6, 2012.
[10] Cohen CB, Cohen PJ. International stem cell tourism and the need
for effective regulation. Part II: Developing sound oversight measures and
effective patient support. Kennedy Inst Ethics J. 2010 Sep;20(3):207-30.
[11] Alleman BW, Luger T, Reisinger HS, Martin R, Horowitz MD, Cram P.
Medical tourism services available to residents of the United States. J Gen
Intern Med. 2011 May;26(5):492-7.
[12] Neuralstem, Inc. Dr. Eva Feldman, Principal Investigator, Presents
Interim Data on Neuralstem ALS Trial. Company press release. September 27,
2011. Available at:
http://investor.neuralstem.com/phoenix.zhtml?c=203908&p=irol-newsArticle&ID=1610372&highlight=.
Accessed: March 6, 2012.
[13] Meirelles Lda S, Nardi NB. Methodology, biology and clinical
applications of mesenchymal stem cells. Front Biosci. 2009 Jan 1;14:4281-98.
[14] Caplan AI, Correa D. The MSC: an injury drugstore. Cell Stem Cell.
2011 Jul 8;9(1):11-5.
[15] Burgess, S. FDA Approves a Cellular Immunotherapy for Men with
Advanced Prostate Cancer. U.S. Food and Drug Administration press release. April
29, 2010. Available at:
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm210174.htm.
Accessed: March 6, 2012.
[16] Schmidt C. FDA approves first cell therapy for wrinkle-free
visage. Nat Biotechnol. 2011 Aug 5;29(8):674-5.
[17] Geron Corporation. Geron presents data from GRNOPC1 trial at
international conferences on spinal cord medicine and rehabilitation. Company
press release. June 7, 2011. Available at:
http://www.geron.com/media/pressview.aspx?id=1271. Accessed: March 6, 2012.
[18] Keirstead HS, Nistor G, Bernal G, Totoiu M, Cloutier F, Sharp K,
Steward O. Human embryonic stem cell-derived oligodendrocyte progenitor cell
transplants remyelinate and restore locomotion after spinal cord injury. J
Neurosci. 2005 May 11;25(19):4694-705.
[19] Hütter G, Nowak D, Mossner M, Ganepola S, Müssig A, Allers K,
Schneider T, Hofmann J, Kücherer C, Blau O, Blau IW, Hofmann WK, Thiel E.
Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N
Engl J Med. 2009 Feb 12;360(7):692-8.
[20] Barre-Sinoussi, F. Toward an H.I.V. Cure. New York Times. June 3,
2011. Available at:
http://www.nytimes.com/2011/06/04/opinion/04iht-edsinoussi04.html. Accessed:
March 6, 2012.
Business & Investment Opportunities
YourVietnamExpert is a division of Saigon Business Corporation Pte Ltd, Incorporated in Singapore since 1994. As Your Business Companion, we propose a range of services in Consulting, Investment and Management, focusing three main economic sectors: International PR; Healthcare & Wellness;and Tourism & Hospitality. We also propose Higher Education, as a bridge between educational structures and industries, by supporting international programs. Sign up with twitter to get news updates with @SaigonBusinessC. Thanks.
This comment has been removed by the author.
ReplyDeleteOne post for all cure. This is a great way of writing such a post where one can come across this and get to know about all the diseases at once.
ReplyDeleteParkinson's Stem Cell Therapy