More on reversing Type 1 diabetes
This past summer, I went on an article-printing spree, and one of the things I printed was this NYTimes article about the work of Dr. Denise Faustman, a diabetes researcher out of MGH in Boston. I read it early last week, and had been idly wondering what became of her research, thinking I should dig and see if anything newer had happened. Fast-forward to last night, I was cruising digg, and I came across more results involving the same protocol that she used back in 2003.
In March of this year, three other labs confirmed that Dr. Faustman's protocol could reverse Type 1 diabetes in non-obese diabetic (NOD) mice. Those results were inconclusive on the role of spleen cells in the recovery of insulin-producing pancreatic islets. The new data from the NIH provide a fourth confirming study, and more significantly, the role of spleen cells in islet regeneration.
In the 2001 and 2003 studies, Faustman and colleagues treated end-stage nonobese diabetic (NOD) mice with Freund's complete adjuvant, a substance that suppresses the activity of the immune cells that destroy islets in type 1 diabetes. They also introduced donor spleen cells to retrain the immune system not to attack islets and found that the protocol not only halted the immune destruction caused by diabetes but also allowed the insulin-producing pancreatic islet cells to regenerate. Evidence indicated that the spleen cells were the source of at least some of the regenerated islet cell and hastened the restoration of blood sugar levels.
The direct contribution of spleen cells to islet recovery, first described in the 2003 study, is confirmed in the current work. NIH researchers used cell lineage tracking in the form of Y-chromosomal fluorescence in situ hybridization (FISH), in combination with insulin staining, to follow the fate of male spleen cells transplanted into female recipients. The female mice that received male donor cells consistently showed Y-chromosome-positive insulin-producing islet cells, indicating that the introduced spleen cells contribute to islet recovery. The current study also showed that the degree of spleen cell contribution is influenced by mouse age at the start of treatment. Spleen cells appear to contribute to islet recovery more in mice who are older and with more advanced diabetes compared with younger mice with less advanced diabetes, in which regeneration of remaining islets may be the dominant mechanism.
With four studies confirming the success of the diabetic reversal, I am wondering when Phase I human trials will begin. From an economic standpoint, FCA and BCG are both good choices, since they are both orphaned drugs. FCA is incredibly old — Dr. Freund, the guy who created it, died in 1960.
While I'm glad to see the success of these studies, it's still a long way from mice to people. I have my doubts about the side effect profile of this treatment as well. FCA is a biologic made (usually) from killed M. tuberculosis, and is forbidden for use in humans. It has a high incidence of painful reaction and potential tissue damage. So that leaves BCG, a similar, but less potent biologic made from M. bovis, found in TB vaccines. The NYT article states that BCG was used in Dr. Faustman's 2003 work, but the original research paper (PDF) indicates that it was actually FCA.
This leaves me wondering two things: 1) will BCG have a similar effect and 2) if BCG is not successful, will FCA be approved for use in humans?
[tags]Medicine, diabetes, type 1 diabetes, fca, bcg, biochemistry, physiology[/tags]
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