Inhaled Insulin Forms Toxic Pulmonary Amyloid Aggregates
A recent article (August 2010) investigating the effects of inhaled insulin in mice raises concerns for humans. Previous studies investigating the relationship between altered pulmonary function and the use of inhaled insulin have focused on the generation of antibodies toward insulin or with pulmonary inflammation and subsequent airway remodeling. This study demonstrates "that inhaled insulin rapidly forms amyloid in the lungs causing a significant reduction in pulmonary air flow." [My guess is denial.]
It is well known that interfaces, such as polar-nonpolar or liquid-air, play a key role in triggering protein aggregation in vitro, in particular the aggregation of peptides and proteins with the predisposition of misfolding and aggregation. Here we show that the interface present in the lungs predisposes the lungs to form aggregation of inhaled insulin. Insulin inhalers were introduced, and a large number of diabetic patients have used them. Although inhalers were safe and effective, decreases in pulmonary capacity have been reported in response to inhaled insulin.
We hypothesize that the lung air-tissue interface provides a template for the aggregation of inhaled insulin. Our studies were designed to investigate the harmful potential that inhaled insulin has in pulmonary tissue in vivo, through an amyloid formation mechanism.
Our data demonstrate that inhaled insulin rapidly forms amyloid in the lungs causing a significant reduction in pulmonary air flow. Our studies exemplify the importance that interfaces play in protein aggregation in vivo, illustrating the potential aggregation of inhaled proteins and the formation of amyloid deposits in the lungs. These insulin deposits resemble the amyloid structures implicated in protein misfolding disorders, such as Alzheimer's and Parkinson's diseases, and could as well be deleterious in nature.
I am finishing listening to their Q3 call now. I have not followed the company closely but found a couple things interesting.
. In the remarks before Q&A (after the opening and financials) a member a management spent a good 5 minutes talking about why their product is NOT exubera. Which I would have thought nothing of if this were say 2 years ago after Pfizer gave up on it. It was amusing to hear them say everyone understands this except wall st. :-). . They said even if they do get approved this year they wouldn't be in a position to sell it till 2H '11. . They have to do some sort of EKG study for the MAA.
I don't follow the company at all but these three things led me to speculate that another CRL may be more likely then a straight approval. While I realize they have potentially a huge market opportunity I can't seem to reconcile that with their current market cap (they have a fair amount of debt!). They mentioned a phase 2 study in melanoma but I think that is all they have. So despite managements contention otherwise I think wall street is valuing them like they have some chance at success.
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