Friday, October 9, 2015

Understanding the link between CFTR and Insulin Function--NACFC 2015

Back to business. Time for one quick summary before I head to a special dinner.

Impact of CFTR on Beta cell Function in the Pancreas--presented by Dr. Antoinette Moran.     
I found this talk really interesting and hopeful.  Development of cystic fibrosis related diabetes is extremely common, and the risk increases with age.  CFRD places an additional large treatment burden on patients, and is associated with a number of negative health outcomes.

Abnormal insulin secretion has been shown to begin very early in life—even in children with normal oral glucose tolerance tests.  

This early abnormality led the researcher to question whether the abnormality was present at birth (an intrinsic defect), or developed over time (acquired defect).  Studies using the CF ferret model show that the animals are born with abnormalities—suggesting that this is an issue present at birth. 

With this knowledge in hand, Dr. Moran was curious to examine the link between CFTR function and insulin secretion.  The link between exocrine function of the pancreas (the release of digestive enzymes) and the presence of functional CFTR is fairly well understood.  The same basic mechanism of mucous dehydration and mucous plugging that causes scarring in the lungs, also leads to ductal blockages in the pancreas--thereby impairing digestive enzyme secretion.  The connection between CFTR and endocrine function (insulin secretion), is still being uncovered.  The question Dr. Moran posed in this study was whether restoration of CFTR function with a drug like Kalydeco might be able to improve insulin secretion, and prevent or delay the onset of CFRD. 

First, Dr. Moran set out to determine whether CFTR was, in fact, present in the insulin secreting beta cells in the pancreas.  Evidence is not 100% conclusive, but highly suggests that CFTR is in fact present in these cells.  

The role of chloride transport (by way of CFTR), has never been included in the classic model of insulin secretion.  

Dr. Moran believes that there is sufficient evidence to update this model to include the role of the chloride channel.

Ultimately, this study examined the insulin secretion of a small group of patients before, and after one month of therapy with Ivacaftor.


As shown in the bar graph, treatment with Ivacaftor produced a significant improvement in insulin secretion.  This is "tantalizing evidence" that correction of CFTR with a modulator drug like Kalydeco has the potential to delay or prevent the onset of CFRD.  Dr. Moran noted that while Type II Diabetes develops differently than CFRD, there may be potential to augment insulin secretion for this group as well with amplification of CFTR function.

While there is certainly more work to be done in this area of study, I walked out of the room with the hope that Kalydeco may help prevent CFRD for my son Brady and many others.

1 comment: