Technology : Do-it-all protein helps kidney repair

2019-02-27 05:10:03

By Andy Coghlan RATS with severely damaged kidneys can be restored to health with a protein already used to repair bones, cartilage and eye tissue. This versatile substance, called osteogenic protein-1 (OP-1), helped the animals’ kidneys recover whether they had been damaged suddenly through acute renal failure, or progressively through chronic kidney disease. Creative BioMolecules, the company developing the protein in Hopkinton, Massachusetts, hopes that it will reverse chronic kidney damage in people who at present have to rely on dialysis machines. The company also expects OP-1 to save people who might otherwise die from kidney failure following heart attacks, accidents and other traumatic events in which the blood supply to the kidney is interrupted. No reliable treatment exists for kidney conditions, and a million people around the world depend on dialysis machines. At a conference this month in Washington DC, the company and its academic associates described their success in using OP-1 to treat acute kidney failure in rats. Typically, a third of the control animals died, whereas all the animals injected with the protein survived. Joe Bonventre and his colleagues at Harvard Medical School showed that concentrations of waste products such as creatinine and urea, which accumulate in damaged kidneys, returned to normal in the organs of animals receiving the protein. In the acute kidney failure that follows trauma, most of the damage occurs when the blood supply to the organ resumes. White blood cells called macrophages flood into kidney tubules and begin destroying tissue. While the reasons for this are not entirely understood, Charles Cohen of Creative BioMolecules suggests that macrophages may be “cleaning up” oxygen-deprived cells that they see as defective, even though the cells could recover. “The protein seems to interfere with the ability of macrophages to attach to the walls of the tubules,” says Cohen. If the macrophages are kept at bay, kidney cells survive and the organ recovers. Results have been equally encouraging in rat experiments that mimic chronic kidney disease. “Untreated animals usually die after three months, but the treated animals live on,” says Cohen. Earlier experiments have already indicated that OP-1 plays an important part in kidney growth. These experiments knocked out the gene for making OP-1 before the animals were born. The rats hardly developed kidneys at all, and most of them died after 10 days or so. But not all specialists are convinced of OP-1’s potential for treating patients with kidney failure. “I’m pretty sceptical,” says Robert Wilkinson, professor of renal medicine at the University of Newcastle upon Tyne. Most people with acute kidney failure eventually recover with the help of dialysis machines, he says. In cases of chronic disease, however, he thinks the approach may slow down the onset of irreparable scarring known as fibrosis. Testing of OP-1 for human bone and cartilage repair is already well advanced (see New Scientist, Science, 18 December 1993, p 20). Cohen says that the protein acts on primitive cells from the bone marrow called stem cells, instructing them to become different types of cells in all kinds of damaged tissue, where they tend to accumulate. Cohen says he does not know of any reason why OP-1 therapy would not be feasible for repairing other organs, including the liver,