Download Mirococept proteins: extending the life of a kidney transplant

Mirococept proteins: extending the
life of a kidney transplant
Researchers at the MRC Centre for Transplantation at King’s College
London have developed a technique that could both significantly extend
the duration of a kidney transplant and increase the organ’s condition
and shelf life, addressing the pressing demand for donor kidneys.
Only about half of transplanted kidneys are still
functioning after 10 years inside the patient, around
one-third of the time a transplanted kidney should
last. Five to 10 per cent of transplants fail within one
year. This means that the number of people requiring
second transplants greatly increases the overall
number of patients on the donor waiting list. As at
September 2013, this number was 5,875, however, in
2012/13, only 1,750 kidney transplants took place1.
for more than 24 hours.
Immune system
Mirococept proteins
The reason for this failure is the body’s own immune
system. When cells of the body meet an ‘intruder’
organism, such as an infection or the cells of a
donor organ, part of the immune system — the
‘complement’ system — is activated, which then
attacks and attempts to destroy the intruder cells.
Ordinarily, to stop the body from attacking its own
cells, this system is controlled by ‘regulator’ proteins
on the surface of its cells. However, when an organ is
removed for transplantation, these regulators are lost
from the cell surface due to the lack of blood flow
and subsequent lack of oxygen. This means that the
complement system will begin to attack the organ’s
own cells, severely damaging it. This is part of the
reason why organs cannot exist outside of the body
This effect is often magnified once the transplant is
complete as the complement system supports the
recipient’s own blood cells in its attack on the organ,
resulting in organ rejection.
People who have received a transplant will take drugs
to suppress their immune system. However, these will
often not completely stop the body from reacting.
To address these issues, the MRC team, led by
Professor Steve Sacks, has developed a method for
coating the inner surface of donor kidneys with
a protective layer of Mirococept proteins — an
artificial replacement for complement regulators. The
application of Mirococept takes just 20 minutes after
the kidney is removed from the donor. To ensure
adherence of the protein to the kidney, the team
have also engineered a ‘tail’, which sticks to the cell
membrane2.
Kidney transplants
The ability of Mirococept to help maintain the
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condition of the organ during transfer would also
greatly increase the number of donor organs suitable
for transplantation. In early tests, only a fifth of organs
worked properly after being stored on ice for 16
hours, compared with more than half of those treated
with Mirococept3.
This new technique, which has recently started
treating patients in the first clinical trial, may drastically
reduce the number of people waiting for a second
transplant, cutting the overall number of people on the
waiting list and potentially saving many lives.
End notes
http://www.organdonation.nhs.uk/statistics/latest_statistics/index.asp
Smith RAG, Koffman G, Chowdhury P, Smith KCG, Watson CJ,
Nicholson ML, Zhou WD, Sacks SH. Membrane-localising complement
inhibitors - clinical progress. Molecular Immunology, 44 (16), 3915-3915,
2007
3
Patel H, Smith RA, Sacks SH, Zhou W. Therapeutic strategy with a
membrane-localizing complement regulator to increase the number of
usable donor organs after prolonged cold storage J Am Soc Nephrol.
2006 Apr;17(4):1102-11. Epub 2006 Mar 1
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