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Stefan Weiss, a professor of
biochemistry at Wits, and his team might be on the brink of a major
breakthrough in the treatment of Alzheimer’s disease and metastatic
cancer. Formerly from the Ludwig-Maximilians-University in Germany,
Weiss and his team in the School of Molecular and Cell Biology
published a groundbreaking review article in Frontiers in Bioscience in
2010 on the association of the Laminin receptor (LRP/LR) with
Alzheimer’s disease and also with prions diseases and cancer.
Alzheimer’s disease
Alzheimer’s disease
has a high incidence rate in South Africa. In collaboration with two of
his masters degree students, Katarina Jovanovic and Danielle Gonsalves,
and a honours student, Bianca da Costa Dias, Weiss’s research on
Alzheimer’s disease, which started in 2010, might be the key to what
the medical world has been searching for, for so many decades.
“We are trying to find an alternative therapy for the
treatment of
Alzheimer’s disease, focusing on therapeutic antibodies directed
against a cell surface receptor or 37kDa/67kDa/Laminin receptor,” he
explains.
“This research is very important for South Africa (SA) because we have
730 000 cases of Alzheimer’s disease patients in the country, mostly
elderly people above the age of 65 and increasing into the 70s and
80s.”
One in five South Africans who is 80 years or above is
suffering from
this disease, which constitutes a very high incidence rate, comparable
to other countries such as the United Kingdom (UK) or Germany where
there is a one in 68 incidence rate.
In their cell biology laboratory on the Wits East Campus
they cultured
human kidney cells, which the team unexpectedly discovered have high
amounts of A-Beta Peptide.
“It so happens that A-Beta Peptide is also one of
causative agents of
Alzheimer’s disease – when it aggregates in Alzheimer patients it
causes the disease,” Weiss explains.
“What we have discovered is that when we treat the
kidney cells with an
antibody against the receptor, the levels of A-Beta peptide go down.
This could be a breakthrough in Alzheimer’s disease.”
Weiss and his team are looking at publishing their
findings soon.
Prions
diseases
Prions are infectious proteinaceous particles that cause
a group of
invariably fatal neurodegenerative diseases. Prion diseases involve the
modification of the prion protein (PrP) and may present as genetic or
infectious disorders. Bovine spongiform encephalopathy (BSE) in cattle,
scrapie in sheep, and Creutzfeldt–Jakob disease (CJD) in humans are
some of the most notable prion diseases.
In 2010 Weiss and his team published a paper in the
Journal of
Molecular Biology about prions and their transmissibility from animals
to humans, entitled Prion interaction with the 37 kDa/67 kDa laminin
receptor on enterocytes as a cellular model for intestinal uptake of
prions.
“We found that by using human enterocytes as a model
system that prions
from elk and deer, and from sheep and cattle might be transmissible to
humans who may then develop a human prion disorder such as variant
CJD,” says Weiss.
Fortunately the infection risk to humans in SA is almost zero, but in
other countries worldwide, including Europe, the UK and the United
States (US), prion disorders pose a far greater problem.
“We found that by blocking the Laminin receptor in the
intestine we may
be able to block the transmissibility because the intestine is the
entry port for prions in both human and animal bodies. It’s like
blocking the bouncer at the entrance to the intestine which allows
prions to enter the human body,” Weiss explains.
The transmissibility factor is new research and no one
else has looked
at it in such detail.
The team published an editorial commentary on oral
transmissibility of
prion disorders in the Journal of Infectious Diseases in 2010.
Cancer
In 2010 Weiss and his team continued their research on
five major
cancer cell types in SA; namely cervical, breast, prostate, lung and
colon cancer cells.
This team comprises two of his Masters degree students,
Aadilah Omar
and Kiashanee Moodley, and one of this Honours students, Raksha Khusal.
“Cancer is a major disease in southern Africa where we
currently have
80 000 – 90 000 cases of many types of cancer, especially lung,
cervical, breast, prostate, colon and oesophageal cancer.”
Once again the Laminin receptor plays a crucial role,
this time in
metastatic cancer – in other words, when the cancer type moves from the
primary site via the bloodstream to a secondary site, which is a major
problem as from here the cancer spreads all over.
“What we found back in 2008 is that antibodies directed
against the
receptor are able to block adhesion and invasion – key events in
metastatic cancer analysed by using fibrosarcoma or skin cancer cells
as a model system. In other words, by blocking the receptor you block
the invasion.”
This time the Laminin receptor or ‘bouncer’ is working
on the basement
membrane of the extracellular matrix, explains Weiss.
“For metastasis to occur the cancer cells must break
though the basal
lamina in the extracellular matrix to enter the bloodstream,” Weiss
explains.
“If you block the receptor then the cells cannot break
though and enter
the bloodstream and so the tumour stays on the primary site, and can
easily be removed with surgery.”
Weiss will publish his significant results on blocking
invasion and
adhesion on cervical, colon, lung and prostate cancer cells by using
antibodies directed against the receptor in 2011.
Apoptosis
Research on apoptosis or ‘programmed cell death’ was
initiated by Weiss
and his team in 2010.
Cancer does not like apoptosis because it wants to
proliferate, hence
apoptosis is blocked by the cancer cells, says Weiss.
In collaboration with Moodley, Weiss is working on
inducing apoptosis.
“The receptor is pro-cancer by two means, so when you
block this
bouncer with an antibody you firstly block metastasis and secondly you
induce apoptosis and target the primary tumour,” he explains.
Key collaborations
Weiss and his team have a key collaboration with a
company in Germany
called Affimed Therapeutics AG in Heidelberg. Together they are working
on the development of antibodies directed against the Laminin receptor
for the treatment of cancer and neurodegenerative diseases.
Other collaborations are with the Medical Research
Council in the UK,
the Scripps Institute of Infectiology in the US and the University of
Sydney in Australia.
Story and
image: WITS newsroom November 2011
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