Recorded: 29 May 2008
So Barret’s Esophagus is a disease where slowly the inner lining of the esophagus, which is the part of the intestine of course, the throat to the stomach, where stomach contents move back into the esophagus. They are very acidic, they have lots of enzymes, and they will cause erosion of the epithelium, and this epithelium slowly converts, for unknown reasons, into a lining that looks much colon epithelium. And this is the large intestine, which is what my lab studies. And we know exactly how to drive these proliferating cells so they ultimately become cancer cells. We know exactly how to drive them out of there stem cell state into a differentiated state. For that it’s actually interesting, we use a drug that has been developed for Alzheimer’s Disease, and these Alzheimer’s patients—many pharma companies have developed them and they all fail in phase one or phase two because of problems in the gut. And we’ve investigated what’s happening and it turns out that these inhibitors of an enzyme called Cama Secratase which produces the plaque in Alzheimer’s, the very same enzyme is active as a key component of an arch pathway, so when you try to block the Alzheimer’s process you also block arch signal. And the only tissue in an adult organism of mammal that’s sensitive to blocking arch signals is the intestinal epithelium. So with these Alzheimer’s drugs you cure Alzheimer, at least it works well for Alzheimer, but you drive all the stem cells in the gut to become goblet cells, mucus producing cells. Which is a side effect that probably will not allow these drugs to ever be commercially exploited for Alzheimer’s. But we are applying them locally now in the esophagus to these Barret’s lesions and there we have the same effect. So all proliferative stem cells of the bad tissues, of the Barret’s tissue, converts into goblet cells and they basically disappear in one big glob of slime. And then what’s left is the normal epithelium.
Yeah, so what happens is, when we take those Alzheimer’s drugs and we formulate them into a drug we can inject into these Barret’s lesions, which are basically colon stem cells, the drugs will convert these colon stem cells into goblet cells. So the bad tissue disappears into one blob of mucus and all that’s left is healthy esophogele epithelium.
Hans Clevers obtained his MD degree in 1984 and his PhD degree in 1985 from the University Utrecht, the Netherlands. His postdoctoral work (1986-1989) was done with Cox Terhorst at the Dana-Farber Cancer Institute of the Harvard University, Boston, USA.
From 1991-2002 Hans Clevers was Professor in Immunology at the University Utrecht and, since 2002, Professor in Molecular Genetics. Since 2002, he is director of the Hubrecht Institute in Utrecht.
Hans Clevers has been a member of the Royal Netherlands Academy of Arts and Sciences since 2000 and is the recipient of several awards, including the Dutch Spinoza Award in 2001, the Swiss Louis Jeantet Prize in 2004, the Memorial Sloan-Kettering Katharine Berkan Judd Award in 2005, the Israeli Rabbi Shai Shacknai Memorial Prize in 2006, and the Dutch Josephine Nefkens Prize for Cancer Research and the German Meyenburg Cancer Research Award in 2008. He obtained an ERC Advanced Investigator grant in 2008. He is Chevalier de la Legion d'Honneur since 2005.