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 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 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.
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.
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.
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.