- A Cure for Diabetes? (2)
- Clinical Practice (3)
- Conference Report (2)
- Current Research (30)
- Diabetes in Popular Culture (2)
- Diabetes in the Press (6)
- Diabetes Technology (3)
- Diatribe (1)
- Guest Essays (4)
- Islet Sheet Updates (13)
- Letters (2)
- Press Release (1)
- Scott's Opinion (22)
- The Marat/King Dialogues (8)
- Type 1 Diabetes Classic (5)
- Uncategorized (4)
July 4th, 2011
The American Diabetes Association held its annual Scientific Sessions last week in San Diego. Everybody else in the Islet Sheet research group had work to do so I attended alone. Next time I will summarize all the presentations I found interesting. This week I will fill you in on the poster that made the front page of the Wall Street Journal.
First Clinical Report on BCG Islet Regeneration Study at Harvard
An attempt by Harvard researcher Denise Faustman to cure fully developed autoimmune diabetes in adults has attracted much interest because it is the only immune therapy not focused on newly diagnosed diabetics (who retain significant islet function). BCG vaccine has been in use for decades and is generally regarded as a safe treatment for tuberculosis. I think BGC is a worthwhile clinical study because the risk-reward is so favorable: a safe biologic might revive islet function in autoimmne diabetes. However, based on my understanding of human immune function and diabetes I have regarded this approach is a long-shot very unlikely to work. First clinical results were presented at the American Diabetes Association meeting in late June. After seeing the ADA poster and discussing these interesting new results with Dr. Faustman I think BCG has better odds than before.
The basic idea is that the natural cause of autoimmune diabetes is auto-reactive T cells, the cells ones that actually kill beta cells in the islets. Dr. Faustman hypothesized that the immune modulator TNF will disable these cells permitting islet regeneration in the reduced level of auto-reactive T cells. Animal studies supported the concept. However, clinical administration of TNF presented practical and regulatory difficulties. So she decided to administer a relatively safe drug, BCG, which in known to induce TNF as part of its activity.
The study data have some serious difficulties. An unlucky randomization and an unlucky EBV infection in a control mean that the effect might well disappear in a large study now underway. EBV is a virus that affects the immune system and, among other things, causes secretion of THF. This patient seems to have responded to the unlikely EBV infection early in the study period (like two of the three treated with BCG) by increasing islet function. The other problem with the controls is that two of three had functioning islets, so were not fully autoimmune diabetes. It has emerged in the last ten years or so that some people diagnosed with autoimmune diabetes die decades later with small numbers of functioning islets, and these people tend to have fewer diabetes complications. This subpopulation is thought be by around 5% to 10% of all type 1 diabetes. So landing two such imperfect diabetics out of three controls if pretty unlikely! One of three controls had an unusual viral infection and two had small numbers of functioning islet cells, enough to be detected.
The only reason the C peptide was detected is that the study used a new ultra-sensitive C peptide assay, much more sensitive than the assay used to screen diabetic study participants. The assay showed that most of the type 1 diabetics had less than 4 picomolar (pM) C peptide in their blood. The ’spikes’ of C peptide were on the order of 4-5 pM, very low, but probably real (but far too little insulin secretion to make any clinical difference.)
Dr. Fasutman’s plan is the give more and larger doses so that the initial regeneration will serve as a base for further regeneration, fish-ladder style, so that insulin secretion will become clinically useful with repeated dosing of BGC. This might work but my worry is that the auto-reactive T cells will win the war. But congratulations to Dr. Faustman and her research group for intriguing data hinting at a therapy that truly would be a cure.