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Cystic Fibrosis and Niemann Pick Type C Linked Through Cholesterol Abnormalities and cAMP Cell Signaling Pathway

April 26, 2009 by  
Filed under Cystic Fibrosis, Related Diseases

Girl with CF A few months ago, I wrote a blog about the connection points between Duchenne Muscular Dystrophy (DMD) and Niemann Pick Type C (NPC) and how more research dollars are needed for collaborative research projects between the two deadly diseases. Today, I am writing about the connections between Cystic Fibrosis (CF) and Niemann Pick Type C. Cystic Fibrosis (CF) is the most common, fatal hereditary disease in the U.S.  CF is a disorder of the cells that line the lungs, small intestines, sweat glands and pancreas. Sticky, thick mucus contributes to the destruction of lung tissue and impedes gas exchange in the lungs. It also prevents nutrient absorption in the small intestine, and blocks pancreatic ducts from releasing digestive enzymes.  I am not going to get into all of the horrible symptoms of Niemann Pick Type C  — simply imagine a bedridden child with complete paralysis of the eyes and severe dementia and you’ll get the picture. Not exactly the life I dreamed of for my beautiful twins, Addi and Cassi. The CFTR gene is located on chromosome 7, while the Niemann Pick Type C gene is located on Chromosome 18. What do these diseases have in common if the disease causing gene mutations are on different chromosomes? Pathways! Both the CFTR gene and NPC1 gene are regulated by the cAMP pathway and researchers at Case Western Reserve University are proposing that Cystic Fibrosis and Niemann Pick Type C cells chronically activate portions of the cAMP pathway to try and restore either CFTR or NPC1.   The chronic activation of the cAMP pathway could lead to cholesterol accumulation, inflammation and oxidative stress. Interestingly, regulation problems in the cAMP pathway could also be involved in other diseases such as Parkinson’s.


I am sure there are many parents in the Cystic Fibrosis community (and possibly many researchers and doctors!) who have no idea that cholesterol processing abnormalities are involved in Cystic Fibrosis or that CF and NPC share similarities. Interestingly, an experimental medication that Addi and Cassi are taking called Zavesca (Miglustat) which is made by Actelion may provide a therapeutic benefit for Cystic Fibrosis patients.  Zavesca is a substrate reduction therapy and Actelion is currently running a small pilot trial for CF patients. Niemann Pick Type C seems to combine the worst of all these larger diseases – from progressive dementia to ataxia and muscular problems to pulmonary issues. Soon to be published works shows that the HIV/AIDS virus requires the Niemann Pick Type C gene to assemble in the body.   What is the common theme here — cholesterol! I hope that Alzheimer’s and Parkinson’s researchers studying the cAMP pathway will start to look at how rare childhood diseases like CF and particularly Niemann Pick Type C can shed light into these more common diseases that affect millions. Maybe the NIH will sponsor a cAMP pathway workshop to bring together researchers from different disease states to collaborate on this critical cell signaling pathway since it is involved in so many illnesses. We need collaboration across different diseases that are interrelated find cures for people!


2 Responses to “Cystic Fibrosis and Niemann Pick Type C Linked Through Cholesterol Abnormalities and cAMP Cell Signaling Pathway”
  1. I completely agree! The possibilities are endless if we work together. My 18-month-old daughter, Gwendolyn, has Spinal Muscular Atrophy Type 1 — the leading genetic killer of children under 2. In our journey we have been encouraged by how much is known, and by how research is heading in such a positive direction with the potential to benefit millions. We hope to help push research over the hump for SMA, for CF, for DMD, for ALS, for NPD, and many other diseases. There is promising legislation in Congress that has the potential to help all of these diseases. We are hopeful. Consider signing the petition in support of this bill:

    • chris says:

      Hi Victoria:
      I have signed the petition — thanks for bringing it to my attention. I am sorry to hear about Gwendolyn and her SMA — we all must continue to fight together!

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