Thursday, August 24, 2006

Type 1 Diabetes: a cure? (in mice)

drj writes: "Type 1 diabetes is the culmination of an immune-mediated destruction of the insulin-secreting beta cells, resulting in a loss of blood sugar regulation (normoglycemia). NOD (non-obese diabetic) mice often suffer a similar disease, perhaps due to a proteasome defect that reduces nuclear factor activation and alters lymphocyte development. Kodama and colleagues here demonstrate the potential of one strategy to cure diabetes - by stopping the immune attack and allowing regeneration from residual beta cells or progenitor cells. While maintaining normoglycemia with a beta cell transplant, they “reeducated” the immune system of diabetic NOD mice by treatment with an immune activator (complete Freund's adjuvant) and repeated infusions of normal (non-NOD) spleen cells. After 6 weeks of twice weekly infusions followed by removal of the beta cell transplant, islet structures and functional beta cells could be found within the NOD pancreas and the mice maintained normoglycemia for over 9 weeks. The authors believe these findings suggest a promising therapy for human diabetes, avoiding the complications of islet transplantation or stem cell culture.
PubMed Kodama et al. Science 302:1223-1227 (2003)
"Islet Regeneration During the Reversal of Autoimmune Diabetes in NOD Mice" Shohta Kodama, Willem K├╝htreiber, Satoshi Fujimura, Elizabeth A. Dale, Denise L. Faustman (posted originally on MedDot.org Jan 17, 2004)

4 comments:

Anonymous said...

My, off the top, "issues"

Three concerns with this report:

(1) Figure 1 shows no control for NOD mice not treated with splenocytes.

(2) Their control for lymphocyte 'contamination' in the Y-chromosome FISH experiments (Figure 3) is weak because inflammation and lymphocyte infiltration occurs in the pancreas but not the 'control' organs (liver, brain, kidney).

(3) According to Figure 4, both CD45+ (lymphoid) and CD45- (non-lymphoid) cells cure diabetic NOD mice. However, CD45- should not be effective at reeducation, and progenitors should be infrequent among CD45+ cells. This result weakens the working hypothesis (such as it is) offered by the investigators.

Anonymous said...

Re:My, off the top, "issues"

Dr. Faustman's recent apeal to the Immunlogy/T1D community that she can "cure" T1D with a $11 vial of BCG, a FDA approved vaccine is ignoring results from a peer reviewed randomized clinical trial published in Diabetes care in 1999. Effect of Bacillus Calmette-Guerin Vaccination on New Onset Type 1 Diabetes. Senior author Peter Chase M.D. Diabetes Care Vol. 22 Number 10 October 1999. pp 1703-07. "Conclusions-Vaccination with BCG at the time of onset of type 1 diabetes does not increase the remission rate or preserve beta cell function".

Reuel said...

Re:My, off the top, "issues"

for the link-challenged among you, here is the PubMed link [nih.gov]. Heck, go the whole way to the original article, Allen et al. "Effect of BCH Vaccination on New-Onset Type 1 Diabetes", here [diabetesjournals.org].

-- parasitic sig, contributing nothing --

Reuel said...

proteasome? NF-kappaB?

There are several genes contributing to the development of type 1 diabetes in NOD mice. A recent review by Ikegami et al [nih.gov] discusses HLA-A and -E as candidate insulin dependent diabetes-1 (Idd1) genes mapping within the major histocompatibility complex (MHC), not the proteasome subunits. Their data also suggest a contribution of IL2 alleles, candidates for Idd3.
Wucherpfennig
[nih.gov] also discusses similarities between MHC alleles of the NOD mouse (I-A(g7)) and humans (DQ2, DQ8). Surprisingly,
Ma et al.
[nih.gov] actually showed administration of dendritic cells deficient in NF-kappaB activity cured NOD mice. Taken together, the evidence is weak that a proteasome defect is a cause, nevermind the cause, of disease in NOD.
-- parasitic sig, contributing nothing --