Cause of severe renal disease found
Children with this disease suffer from rickets, their bones fail to form properly, they suffer from skeletal deformities and cannot develop normally. In adults the bones are soft. These patients, children and adults, have one thing in common: they suffer from a severe renal disease, so-called Fanconi’s syndrome. The characteristic of this disease, which can manifest itself in a variety of forms, is vitamin D deficiency. In this disease the body is unable to utilize vitamin D. Attempting to treat the condition by giving vitamin D tablets is useless. The patient’s kidneys simply excrete the vitamin, which regulates calcium and bone metabolism. Recently, Dr. Thomas Willnow, a Heisenberg scholar and research group leader at the Max Delbrück Centre for Molecular Medicine (MDC) in Berlin-Buch, has discovered one of the causes which lies behind this metabolic defect. In recognition of his research on lipid metabolism Dr. Willnow has been awarded (30th October, 1998) the Heinrich Wieland Prize worth 50.000 DM in a ceremony which took place in Munich.
Dr. Willnow has been investigating a binding site (receptor) on the kidneys the function of which had remained unknown until recently. The receptor is located at a fairly critical site in the kidneys, namely the proximal tubules. These are adjacent to the renal glomeruli, millions of tiny organelles, which filter small molecules out of the blood including toxins as well as fat soluble vitamins such as vitamin D. Dr. Willnow was able to show that the receptor he was studying acted as a sort of collecting point for the vitamin D filtered from the kidneys. Before it is literally washed past it, the receptor, known technically as megalin (gr. mega= large), intercepts the vitamin D and returns it back into circulation via the cells which coat the renal tubules (epithelial cells).
“Now we know why patients with renal disease have bone defects,” announced Dr. Willnow, explaining the significance of his research findings. The function of the megalin receptor was demonstrated in mice (knock-out mice) in which the gene for this binding site had been inactivated. Mice treated in this way are no longer able to recycle vitamin D but excrete it in urine instead.
Double cover
In addition, using this knock-out approach, Dr. Willnow has been able to establish the function of a new receptor on liver cells. This is the so-called LDL-receptor related protein (LRP). This protein sweeps up dietary cholesterol from the circulating blood and channels it to the liver where it can be disposed. In collaboration with the research team of Dr. Joachim Herz at the Southwestern Medical Center in Dallas, Texas, he showed at the same time that the liver has a dual system ensuring the efficient disposal of cholesterol arising from the diet. “Dietary cholesterol is particularly harmful since it is stored in the vessels. Therefore, the body has to act as quickly as possible to make sure that this sort of storage just does not happen”, explained Dr. Willnow in describing this dual system. In association with the LRP receptor, this dual system also involves the LDL receptor which was discovered by the American researchers, Michael S. Brown and Joseph Goldstein (Dallas, Texas), a few years earlier. In 1985 they were awarded the Nobel Prize for Medicine for their discovery.
This recognition of his work by the Heinrich Wieland Prize puts Dr. Willnow in distinguished company. Previous recipients of the award include the Nobel Laureates Brown and Goldstein, who received the Wieland Prize in 1974 as well as Bengt Samuelsson (Stockholm) who won it in 1981. The recipient in 1997 was Prof. Bruce Spiegelman, Harvard University, Boston, USA. The prize is named after the German Nobel Laureate for Chemistry, Heinrich Wieland (born Pforzheim 4.6.1877, died in Munich 5.8.1957). The prize is funded by the Margarine Institute for Healthy Nutrition in Hamburg.
Barbara Bachtler
Press Department
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Strasse 10
13125 Berlin
Phone: +49 (0) 30 94 06 — 38 96
Fax: +49 (0) 30 94 06 — 38 33
e‑mail: presse@mdc-berlin.de
http://www.mdc-berlin.de
Dr. Ingo Witte
Kuratorium für die Verleihung des Heinrich-Wieland-Preises
Gasstrasse 18
22761 Hamburg
Phone: +49 (0) 40 89 40 04
Fax: +49 (0) 40 89 40 06
