Headed off at the pass?
It might be possible to diagnose and prevent one form of diabetes before it strikes
LIFE is not much fun for diabetic children. It involves a lot of pricked fingertips and insulin injections in the arm. Childhood staples such as sweets and fizzy drinks are discouraged. And despite all the suffering and sacrifice, as they age, diabetics nonetheless have an increased risk of blindness, kidney damage and heart trouble. The disease—known as type-1 diabetes to distinguish it from type-2 diabetes, a more widespread disorder which usually afflicts adults above the age of 45—also strikes without warning. One day, out of the blue, an apparently healthy child suddenly becomes insatiably thirsty and starts to urinate continuously.
By then, many of the body's insulin-producing islet cells have been destroyed. But while the onset of the disease seems sudden, the truth is that in many cases tell-tale antibodies have been circulating in the child's bloodstream for years, possibly since birth. What if it were possible to sample these antibodies to identify who was at risk, then intervene before the worst of the damage was done? That is what Yousef Al-Abed proposed earlier this week in a talk delivered to the American Chemical Society, which was meeting in Anaheim, California. He and his colleagues at the North Shore-Long Island Jewish Research Institute in Manhasset, New York, have come up with a molecule that appears to be able to prevent diabetes in young mice.
Type-1 diabetes is a disease of the immune system: for reasons not well understood, a combination of genetic and environmental factors prompt an all-out attack on the insulin-producing islet cells in the pancreas. Inflammation plays a role in starting this process. Some years ago, Dr Al-Abed suggested that a protein known as macrophage migration inhibitory factor (MIF) might make a logical therapeutic target. MIF signals to a network of inflammatory pathways: cutting its lines of communication might halt the inflammation, he reasoned, and perhaps even stop the disease in its tracks. This week Dr Al-Abed announced that he had found a compound called ISO-1 that seems to do just that.
Dr Al-Abed and his colleagues demonstrated two years ago that ISO-1 binds to a particular site on the surface of MIF which prevents it from carrying out its inflammatory behaviour, in the laboratory at least. But whether it would have the same effect in a living organism remained an open question. So Dr Al-Abed treated a group of laboratory mice with a chemical agent called streptozotocin, or STZ, which caused them to experience the high blood-sugar levels that characterise diabetes. Of these animals, those not treated with ISO-1 all developed chemically induced diabetes. But those that were given the drug, which was injected for ten days in the seventh or eighth week of their lives, did not. Dr Al-Abed also investigated the drug's effectiveness on another group of mice that had been genetically engineered to develop type-1 diabetes. Of these, 20 out of 22 were protected. None of the treated mice suffered from any side effects.
Because the ISO-1 molecule is small, Dr Al-Abed thinks it could be easily adapted into a human oral medicine within a few years. Test kits would also have to be developed to find the children who could benefit most. Dr Al-Abed envisages a population-wide screen, like the infant heel-prick test which is used to detect PKU, a metabolic disorder, in newborns. Individuals with high levels of diabetes-related antibodies would be monitored until the levels indicated an impending attack. At that point, the drug would be administered. Costly though such screening would be, it could save a fortune: $100 billion a year is spent treating diabetes in America alone, and while type-1 diabetes accounts for around 10% of diabetes sufferers, it is responsible for around 40% of treatment costs. Most importantly, patients' lives would be immeasurably improved.