Protein Treatments to Cure Type 1 Diabetes?

Proteins are being investigated for use in treating a variety of diseases because they can influence cell behavior by fueling or dampening certain molecular signals, therefore their use may be used to influence the regeneration of certain cells, in the case of diabetes, the pancreatic beta cells. This falls under the broader diabetes research objective to investigate inducing beta cell regeneration. Several methods are now being investigated or reviewed, including (among others), INGAP as well as several other techniques that were seen as useful in beta cell regeneration. If you aren't familiar with INGAP, that story was chronicled a few years ago. To read the background on that, please see the following archived story links below:

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Beta cell regeneration has emerged in recent years as at least a possible element required to successfully reverse type 1 diabetes. Previous medical dogma had dismissed the idea, with the idea (supported by a handful of incomplete studies) that once the damage was done, the beta cells are history and cannot be replaced except by using transplantation. But in recent years, a number of new studies have since proven that long-held belief was incorrect.

At the 2005 ADA Scientific Sessions in San Diego, UCLA's Dr. Peter Butler and colleagues published results from an extract under the title "Evidence for Sustained Islet Turnover in Humans with Long-Standing Type 1 Diabetes" which showed that even patients with long-standing type 1 diabetes (50 years was the longest duration in the test group if I recall correctly) had evidence of beta cell generation, but that the immune system continues to destroy the new cells. Although these results were never published in a medical journal, a small page was published a while back on the now-defunct "Join Lee Now" website. The extract can be found on the Internet Archive Wayback Machine, provided you know the address for what you're looking for in the archive). For simplicity sake, just use this link.) That study, followed by research announced by Joslin and others, have shown there is indeed evidence that even people with long-standing type 1 diabetes still have beta cells which continue to be destroyed in the setting of low-grade inflammation.

Yesterday, a press release from the University of Florida announced findings from a study involving the use of proteins a potential therapy for type 1 diabetes. University of Florida (UF) researchers were able to coax liver and pancreatic cells in diabetic mice into producing insulin by injecting the animals with a protein known as Pancreatic Transcription Factor (known more commonly as Pdx1 or simply PDX). The protein itself is not a new discovery, having been investigated and reported in several scientific and medical journals for a number of years now. Pdx1 in turn activates the genes controlling the development of the pancreatic beta cells. The UF research team's novel approach is described online in the journal Diabetes.

Earlier research showed that inserting the Pdx1 gene into liver or pancreas cells can induce insulin production, but most gene therapy methods use viruses to introduce a piece of genetically engineered DNA into cells. The disadvantage of such approaches is that researchers can never be certain the viruses are entirely harmless, Chief Researcher Li-Jun Yang, an associate professor of pathology, immunology and laboratory medicine at UF's College of Medicine said.

The basic idea with protein therapy is that a person's own cells could possibly be reprogrammed to naturally produce the hormone, restoring the body's ability to properly regulate blood sugar levels without having to use a potentially hazardous virus to slip corrective genes into the body or having to transplant pancreatic cells from someone else. That might also eliminate the adverse effects sometimes associated with gene therapy and eliminate the need for lifelong suppression of the immune system so transplanted cells are not rejected, Yang said.

"What's so innovative about UF's approach is the ability to normalize blood glucose levels in diabetic mice simply by delivering Pdx1 protein in the target cells, thus effectively eliminating the side effects associated with gene therapy," Yang said.

"Right now, promoting beta cell regeneration has become such a hot topic," she added. "The trick is to figure out how to trigger glucose-regulated insulin-producing cells to regenerate."

Still, the UF researchers admit that this approach will have to be tested in studies that assess its safety before scientists could conduct patient trials to determine whether it works in people, and those studies that are still years away.

Bear in mind, this was yet another mouse study, so don't get too excited just yet. Still, it IS progress towards treatments which can induce beta cell regeneration. Perhaps, when combined with another therapy to address the problem of ongoing autoimmunity towards the pancreatic beta cells, that will do it. I'm thinking, for example, of the recent deal with MacroGenics, Inc. by Eli Lilly and Company in November 2007 to commercialize teplizumab, a humanized anti-CD3 monoclonal antibody treatment. Another one is Clal Biotechnology Industries Ltd./Teva's DiaPep277 which was announced earlier last year. The latter is slightly different, being a peptide - rather than an antibody - derived from the human protein, HSP60, which could immunomodulate the body's errant immune system. Both were highlighted in my 2007 Wrap-Up and Outlook for 2008 published recently. Oh, and I never mentioned Dr. Faustman's and her colleague, Dr. David Nathan's human clinical trials, also meant to stop the ongoing issue of autoimmunity. I hardly need to elaborate on that one!

One thing I think has become abundantly clear, however, is that any "cure" for type 1 diabetes is likely to consist of several distinct components. It may not be a single surgery, transplantation or treatment, but multiple surgeries, transplantations of treatments needed to address several different problems. I am not the only one to reach this conclusion. Dr. Camillo Ricordi at the University of Miami's Diabetes Research Institute and his colleagues also have gone on the record as stating this, too. Regardless, another piece to the diabetes puzzle is slowly, but surely, being chipped away!