Sunday, April 30, 2006

Yet Another "Potential" Cure For Type 1?

Earlier this week, the internet was abuzz with news that researchers now believe that a cocktail of drugs might be a successful (and necessary) approach to curing type 1 diabetes. Of course, the research was only tested on the nonobese diabetic (NOD) mouse, which is the most frequently used animal model for human type 1 (immune-mediated) diabetes. But I've seen similar promises of potential cures over the last 30 years, so I will hold off on getting too excited at the moment. For complete details from the scientific journal that these findings were published in, please see the following article published in the Journal of Clinical Investigation:

Damien Bresson, Lisa Togher, Evelyn Rodrigo, Yali Chen, Jeffrey A. Bluestone, Kevan C. Herold, and Matthias von Herrath; "Anti-CD3 and nasal proinsulin combination therapy enhances remission from recent-onset autoimmune diabetes by inducing Tregs"; J. Clin. Invest., Apr 2006; doi:10.1172/JCI27191.

First, we need to be careful about getting too excited about cures that work in mice, because if I were a diabetic mouse, I would likely be cured by now, but I am human and few animal cures ever seem to translate into cures in humans. How many mouse diabetes cures have been successfully translated into human cures? Not one so far.

An important discovery recently published in the Proceedings of the National Academy of Science ( see article here ) showed that the internal structure of human insulin-producing islet cells is dramatically different than the well-studied islets in rodents, dispelling a very basic assumption used by researchers for decades. The finding, by researchers at the Diabetes Research Institute at the University of Miami Miller School of Medicine, showed that the composition of a human islet is so different than that of the rodent model that it may no longer even be relevant for human studies. This means that research must be conducted differently if it is to benefit people living with diabetes. Thus, while the basic problem of an immune system conducting "friendly fire" on healthy tissues is relevant, it is now understandable why so few of the numerous mouse cures ever translate to human cures.

Fundamentally, the proposed approach of using a cocktail to address the issues of autoimmunity, islet regeneration, and other issues is sound. Furthermore, only recently has that approach started to be investigated seriously. I was quoted in an internet message board about 4 years ago saying that someone should really pursue a trial with the work pioneered by Jeffrey Bluestone at the University of California San Francisco using monclonal antibodies for immunomodualtion combined with islet transplantation or regeneration (such as INGAP, see my New Year's post for more info on that) as most efforts previously address only 1 of several defects in the body. Finally, researchers are doing just that! If for no other reason, I believe the most recent work is important in that it proposes this multi-pronged approach to a cure, rather than a single "magic bullet".

This is not the only research into this approach. There are currently studies among newly diagnosed type 1 patients investigating the use of monoclonal antibodies along with islet transplantation, and the highly-popular research conducted by Massachusetts General Hospital (MGH) sponsored by the Iacocca Foundation into "retraining" the faulty immune system also aims to do the same thing. The key difference is that the MGH research found that once the immune system defect was corrected, the body was capable of regenerating its own islets, and collaborating research in mice did find this to be true, although it did not enjoy the same rate of success. But human trials need to occur to see if the same results can be replicated in humans. Regardless, all of these developments do suggest that science may finally be acknowledging that several treatments addressing multiple problems are required to address this complex condition known as type 1 (or juvenile) diabetes.

I truly hope the latest finding in California contributes important knowledge advancements that will actually enable a real cure to be developed sooner rather than later, but I will put my excitement for the latest finding on hold until there is more work to substantiate it.


BetterCell said...

Hello Scott......This is a step in the right direction regarding immune modulation eventhough it only (at this time) applies to "newly acquired T1DM". It is the rest of us who are in need of a way to have insulin being produced without an overzealous immune system. I have also posted a response to your reply on my site.

Scott S said...

Newly diagnosed patients still maintain measurable endogenous insulin production, therefore most of the trials revolve around preserving the remaining beta cell functionality. However, as the results from the 2005 ADA Scientific Sessions demonstrated "sustained islet turnover" even among longstanding type 1 patients (some in that study had it as long as 60 years). Hopefully, they will begin testing on long-standing T1DM patients in the near future.

BetterCell said...

The problem with the "near future" is that it is all relative depending on what mark one is standing on in the line continuum to progress in medical research & benefit.
Thus the testing in the near future can be in 5 years or 200 years. There are too many variables including money, research priorities, politics, and above all intelligence.

Scott S said...

That's one reason the MGH research has become so incredibly popular, because they plan to begin testing on longstanding T1 patients, and the plan is to begin later this year. Given that the confirming research on mice was successful, but less successful than Dr. Faustman's initial results, there is still potential there, but people need to be realistic about the potential, but every contribution to science is important.