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Pro-Test: standing up for science
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Archives for: January 2008

24/01/08

Permalink 12:09:22 pm, by Tom, 430 words, 2073 views   English (UK)
Categories: Information

Transplants without immunosuppression?

A major problem with transplant operations is that recipients of new
organs need to take powerful immunosuppressive drugs for many years
after the operation to prevent organ rejection. These drugs essentially
turn down the immune system and can contribute to high blood pressure
and cancer. This week two groups of scientists, led by Dr. David Sachs
in Massachusetts and Professor John Scandling in Stanford, have
published studies in the New England Journal of Medicine describing how
they reset the immune system in patients to permit kidney transplants
without the need for long term immunosuppressive drug use (1,2). The
techniques used by the different groups differed, though both involved
partial depletion of the recipients T-cells to help prevent rejection
followed by transplant of bone marrow cells from the kidney donor to
induce a state known as mixed blood and immune-cell chimerism which
induces tolerance of the donated kidney by the recipients immune system.

http://news.bbc.co.uk/1/hi/health/7205094.stm

These studies build on decades of experience in laboratory animal
models, alongside information gained from studies of transplant patients
and those treated for cancers of the bone marrow such as leukemia. Early
work by Billingham, Brent, and Medawar showed that transplanted immune
cells could induce tolerance in mice (3) and later studies in mice
demonstrated that such chimerism could be achieved without using
treatments that severely damage or destroy the recipients own immune
system (4). More recently David Sachs and colleagues studied different
protocols for inducing mixed chimerism and immune tolerance in monkeys
to determine which were most successful before undertaking their studies
in human patients(5). These and other animal studies by the
Massachusetts and Stanford groups were vital to the development of
procedures that could be tried in human patients.

Further research is required before these methods can enter widespread
use. The existing patients will be continue to be monitored for any
problems and patients will be enrolled in larger trials. No doubt the
techniques will be refined as clinical trials yield new information, but
the initial results are very promising.

1) Scandling J.D et al. "Tolerance and Chimerism after Renal and
Hematopoietic-Cell Transplantation" NEJM Vol. 358:362-368 (2008).
2) Kawai T. et al. "HLA-Mismatched Renal Transplantation without
Maintenance Immunosuppression" NEJM Vol.358: 353-361 (2008).
3) Billingham R.E. et al. "Actively acquired tolerance of foreign cells"
Nature. Vol.172:603-606 (1953).
4) Sharabi Y. and Sachs D.H. "Mixed chimerism and permanent specific
transplantation tolerance induced by a nonlethal preparative regimen" J.
Exp. Med. Vol. 169:493-502(1989).
5) Kawai T. et al. "Long-term outcome and alloantibody production in a
non-myeloablative regimen for induction of renal allograft tolerance"
Transplantation Vol. 68:1767-1775 (1999).

Paul Browne

21/01/08

Permalink 09:57:03 pm, by Tom, 416 words, 4182 views   English (UK)
Categories: Information

Stem cell hopes for Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a form of muscular dystrophy that
is characterized by decreasing muscle mass and progressive loss of
muscle function, which occurs as a consequence of the absence of the
dystrophin protein. It affects about 1 in 5,000 people and usually
results in death before the age of thirty. We recently discussed how the
mdx mouse model of DMD has contributed to the development of potential
treatments for the disease.
http://www.pro-test.org.uk/b2evo/index.php?blog=7&title=masking_the_cause_of_duchenne_muscular_d&more=1&c=1&tb=1&pb=1
While such treatments are potentially very valuable their disadvantage
is that they can only help a minority of DMD patients who have a
particular defects in the dystrophin gene.

In recent years scientists researching treatments that would benefit all
DMD patients have attempted to use stem cells to replace the muscle
cells that are defective in mouse models of DMD, but until now the
results have been disappointing, with little sign of improved muscle
function. Furthermore there have been concerns that embryonic stem (ES)
cells injected into mice can develop into tumours (1,2).

In a study (3) published in Nature Medicine this week Rita Perlingeiro
and colleagues at University of Texas Southwestern found that by
inducing the expression of Pax 3, a transcription factor which is
thought to kick start muscle development, they were able to coax ES
cells to differentiate into muscle cells. Furthermore by selecting ES
derived muscle cells that expressed the marker protein PDGF-alpha, but
not the marker Flk-1, they identified those that when injected into mdx
mice grafted onto their muscles and significantly improved muscle
strength and coordination. Better still there was no sign of any tumour
formation.

http://news.bbc.co.uk/1/hi/health/7191852.stm

By identifying several requirements for stem cells to develop into
muscle cells that can be safely used to replace those lost in DMD Dr.
Perlingeiro and colleagues have taken an important step towards
developing a stem cell treatment for human use.

1) Fujikawa, T. et al. " Teratoma formation leads to failure of
treatment for type I diabetes using embryonic stem cell–derived
insulin-producing cells." Am. J. Pathol. 166, 1781–1791 (2005). PubMed:
15920163
2) Roy N.S. et al. "Functional engraftment of human ES cell-derived
dopaminergic neurons enriched by coculture with telomerase-immortalized
midbrain astrocytes." Nat Med. 12(11):1259-68 (2006).PubMed: 17057709
3) Darabi R et al. "Functional skeletal muscle regeneration from
differentiating embryonic stem cells" Nat Med. Advanced publication
online: 20 January 2008.
http://www.nature.com/nm/journal/vaop/ncurrent/full/nm1705.html

07/01/08

Permalink 03:33:36 pm, by Tom, 174 words, 2256 views   English (UK)
Categories: Information

Promising results for universal flu vaccine

Just over a year ago we reported that the vaccine development company
Acambis was starting clinical trials of a vaccine that they hope will
confer long lasting protection against all influenza A strains.

http://www.pro-test.org.uk/b2evo/index.php?blog=5&title=animal_research_offers_hope_of_universal&more=1&c=1&tb=1&pb=1

Last week the BBC reported that the results of the initial clinical
trails are very promising, and demonstrated that the vaccine is safe and
immunogenic in human volunteers.

http://news.bbc.co.uk/1/hi/health/7171118.stm

Following on from this success the firm now hopes to undertake larger
trials to evaluate the vaccine's ability to protect against flu in human
populations. Acambis have also reported that in animal tests the vaccine
provided effective protection against the deadly H5N1 avian influenza.
This is a most welcome result since none of the flu vaccines currently
available are expected to protect against a pandemic avian flu strain.

http://www.acambis.com/default.asp?id=2039

Regards

Paul Browne

Stand Up For Science

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