An arthritis drug found to treat type 1 diabetes

July 15, 3:39 PMDiabetes ExaminerRobert Scheinman

Previous Next

Comment Print Email RSS Subscribe

Subscribe

Get alerts when there is a new article from the Diabetes Examiner. Read Examiner.com's terms of use.

Email Address   Include other special offers from Examiner.com Terms of Use

TNF blocking drug

Our body is really a bunch of cell neighborhoods. Like us, they gossip but for them this is how important local news is communicated. One way in which cells talk to each other is by secreting signaling proteins called cytokines. These cytokines bind to receptors on neighboring cells. If there is damage due to trauma or the presence of a parasite or a virus, different combinations of cytokines are secreted and the neighbors respond with their own signals. Eventually the signal makes it to resident macrophages and if things are looking bad, the signal will make it to the nearest lymph node which is sort of the local military base for immune cells. This is just a small part of the enormous network of communication used by different cells. The immune system, in particular, has a huge repertoire of signals – a molecular language, by which the context of the situation is communicated.

All of these various ways in which the context of the situation is communicated creates for us in the medical community, a set of hooks were we can get control of the situation. One very useful hook has been the cytokine family. A number of drugs have been designed to block specific cytokines and these have found their way into medicine to treat certain autoimmune conditions. One of these cytokines is called tumor necrosis factor (TNF). There are now 3 drugs on the market that work by blocking TNF including Embrel, Remicaid, and Humira. More are on the way. The major use for these drugs is in the treatment of Rheumatoid Arthritis and more recently, Crohn’s Disease. Both of these conditions seem to respond well (for about 30% - 60% of patients) to this sort of therapy. Other conditions such as Lupus actually get worse when TNF is blocked. The story for type 1 diabetes (at least in mice) has been complex. Blocking or increasing the TNF signal has had variable results depending primarily as to when the manipulation was performed in respect to the development of the disease (and also where the TNF was being made). The good news was that early blockade of TNF seemed to have good effects on mice that spontaneously develop type 1 diabetes.

These good results in mice have propelled human clinical trials forward and now we have the results of one such trial published in Diabetes Care by Dr. Lucy Mastrandrea and co-workers from the University of Buffalo in New York State. The authors recruited 18 children between the ages of 7.8 and 18.2 who had just been diagnosed with type I diabetes. Half were randomly assigned to receive Etanercept for 24 weeks while half received a placebo. All had normal insulin shots to manage their diabetes during that time. The critical issue here was the timing of the treatment. Generally, right after the drop in pancreatic function that precipitates disease and diagnosis there is what is termed a “honeymoon period”. During this time, beta cell function temporarily improves with the concomitant improvement in insulin secretion. Ultimately, of course, it all falls apart and the patient is dependent on insulin shots. The authors hypothesized that blocking TNF might be beneficial during this honeymoon period and so required these children to begin treatment right after diagnosis. Getting parents to sign on must have been a nightmare as the authors indicated that 266 children who met the criteria would not participate. This was not necessarily over protectiveness as Etanercept produces a profound susceptibility to infection which cannot be easily treated. Additionally, some patients have reported Lupus like symptoms. This was definitely a hard decision for parents.

Luckily, it all worked out. The treatment group saw a 39% increase in insulin secretion while the placebo group saw a 20% decrease. Hemoglobin A1C levels for the treatment group were 5.91 while A1C levels for the placebo group were 6.98. This is significant as 6.5 is the level at which patients become at risk for complications. No one withdrew because of adverse effects. We await the results of a larger trial with great interest.