whoa, Henry, slow down! : ) doesn't anybody read these abstracts?
for example, let's listen to what this says:
"Abstract #:
0111
Presentation Date:
6/14/97
Activation of RXR with Rexinoids (RXR Selective Ligands) Function as
Insulin Sensitizers in Type
II Diabetic Mice
DIANE L. CROMBIE 1,2, JAMES R. PATERNITI 1,2, RICHARD A. HEYMAN1,2, San
Diego, CA, USA.
...
In mouse
models of non-insulin dependent diabetes mellitus (NIDDM) and obesity,
including the ob/ob and db/db mice, RXR agonists
function as insulin sensitizers decreasing hyperglycemia,
hypertriglyceridemia and hyperinsulinemia. Combination treatment with
the thiazolidinedione, BRL49653, further enhances the maximal response
of either agent alone. When RXR agonists are used
during early stages of insulin resistance they block the progression of
NIDDM. At late stages of insulin resistance, these agents
signficantly reduce the amount of exogenous insulin required to reduce
the hyperglyemic state to the euglycemic levels. These
data suggest that activation of the RXR:PPARg heterodimer with rexinoids
may provide a new therapeutic approach as
monotherapy or combination therapy for the treatment of insulin
resistance."
So,
1 - In mouse models of Type 2 diabetes and obesity, RXR agonists (e.g., 268, 1324) reduce insulin, glucose, and triglyceride levels. We know this already from the Nature article last year, but it's worth repeating.
2 - Combination with a TZD (PPARg agonists - best known example is Rezulin) enhances the effect of either used alone. Also known from the Nature article (this may be a presentation of the same study), but worth repeating. This is important data.
3 - During the early stages the disease (in mice), RXR agonists block the development of insulin resistance, and hence the progression of the disease. huh?! very, very good news.
4 - During late stages of insulin resistance, RXR agonists reduce the amount of insulin required to reduce glucose levels (and hence treat hyperglycemia). Also known, but worth restating.
The net is if LGND were able to produce a drug that were tolerable enough for chronic use (still don't know yet ... but major SE with Targretin appears to be triglyceride elevation ... and the earlier stage products appear to reduce triglycerides), one that showed efficacy across the life cycle of Type 2 diabetes, and were marketed by the leading player in diabetes treatments (LLY) ... we could have a very big product on our hands in a number of years.
Peter |
