Sunday, December 4, 2022

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!

Mom Finds Experimental Drug for Twins’ Fatal Cholesterol Condition; FDA Approves Treatment Under Compassionate Use Program

April 20, 2009 by  
Filed under Videos

Good Morning America reports on the Food and Drug Administration’s approval of Addi and Cassi’s compassionate use Investigational New Drug Application to give them intravenous infusions of cyclodextrin, a non toxic sugar compound found in everyday food products. Cyclodextrin may have the ability to remove trapped cellular cholesterol from Addi and Cassi’s brain, liver and spleens.

Cyclodextrin As A Therapeutic “Drug” For HIV AIDS, Niemann Pick Type C and other Viruses

April 16, 2009 by  
Filed under News

Addi and Cassi’s first round of cyclodextrin infusions have been going smoothly at Renown Regional Medical Center in Reno, Nevada.   We’re now into our third day of continuous infusions of hydroxy propel beta cyclodextrin (HPBCD) into the girls’ bloodstreams and they don’t seem to be experiencing any negative side effects.    I feel as if it’s having a positive and immediate effect.  Addi was talking yesterday afternoon and stringing together more than one word — “I like my toys, I’m brave enough, I need your help, “Bye” to Dr. Hastings, and “Ad” for her name Addison.  Even Cassi came out with a few words – “Mommy, No.”     This is quite encouraging to us but we’re not yet sure if it’s a result of the cyclodextrin treatment.

Addi and Cassi resting during cyclodextrin infusions

Addi and Cassi resting during cyclodextrin infusions

Addi and Cassi’s blood work-ups have come back “normal” following the cyclodextrin infusions.  There was a slight elevation in both girls’ eosinophils after 24 hours but it was minor.   We also had to change Addi’s port access needle as it was not working properly and we were unable to draw blood.   Unfortunately, we had to re-install the needle on her chest without any numbing cream.  Ouch!

Addi and Cassi's Cyclodextrin: Renown Regional Medical Center
Addi and Cassi’s Cyclodextrin Being Prepared In Sterile Form: Renown Regional Medical Center

I found out this morning that researchers were looking at the same cyclodextrin (HPBCD) and Niemann Pick Type C disease back in 1996 — 13 years ago!   I received this information from a scientist in Europe and I almost had a heart attack when I read the scientific abstract.

Somehow cyclodextrin research as it relates to Niemann Pick Type C was not thoroughly pursued with all angles exhausted by scientists.   This simply can not happen again — not only for Niemann Pick Type C disease but for HIV/AIDS and potentially other viruses like Herpes that are inactivated and killed by cyclodextrin.

I worry about the future of cyclodextrin research.  We can’t count on pharmaceutical companies to research cyclodextrin or bring therapeutic products with cyclodextrin to people as they are focused on profits and patents on new drugs that take millions of dollars and years to make.   Cyclodextrin is an inexpensive and non-toxic compound that can be deployed tomorrow — far too EASY!   But the HIV/AIDS pharma companies should be watching cyclodextrin very closely.  I believe the smart ones will start investing into research and try and create new patents around cyclodextrin since the Niemann Pick Type C cholesterol gene/protein on Chromosome 18 is the culprit in HIVs ability to assemble itself in the human body.


Very First Glass Infusion Bottles of Cyclodextrin

It’s time that the National Institutes of Health (NIH) Office of AIDS Research or the Centers For Disease Control and Prevention or some other government agency steps in and redirects money into cyclodextrin research to study this potentially life-saving compound that has very broad applications.

I am also asking for help from private citizens and global foundations such as The Gates Foundation, The Clinton Foundation, Elton John AIDS Foundation, amfAR and to step in and help by taking a closer look at cyclodextrin and it’s relationship to cholesterol metabolism and killer viruses like HIV/AIDS.   We must make sure cyclodextrin is properly tested as a therapeutic agent whether money can be made from it or not (which is can be!)

KTVU Reports On New Treatment for HIV/AIDS and Deadly Childhood Cholesterol Disease

April 5, 2009 by  
Filed under Videos

San Francisco Bay Area Television station KTVU Channel 2 tells the story about how HIV/AIDS and rare childhood cholesterol disease are connected and how a promising new treatment with a sugar compound called cyclodextrin could help both deadly diseases. Our thanks to KTVU for airing this 4 minute segment. (April 1st, 2009)

Apo E Gene and Diet

April 4, 2009 by  
Filed under Genetics

All afternoon, I have been thinking about the Apo E cholesterol-related gene and what combination of Apo E genes each person in our family inherited.  The Apo E gene provides instructions for making a protein called apolipoprotein E and it is located on Chromosome 19.   This protein combines with fats (lipids) in the body to form molecules called lipoproteins.   Lipoproteins are responsible for packaging cholesterol and other fats and carrying them through the bloodstream.

Some research suggests there is a connection between the Apo E gene and Alzheimer’s and dementia.   I found out that Addi and Cassi have Apo E gene is 3/3, which is considered "neutral" so this doesn’t explain their dementia.  I think their problems have more to do with insulin factors (they have a glucose metabolism problem in frontal lobe of their brains), oxidative stress, and inflammation and the interaction between genes and nutrients/vitamins.

Research suggests that Apo E genes can influence your predisposition to certain illnesses from Alzheimer’s disease, Parkinson’s disease, heart disease and cancer.   I read that persons with the Apo E 4/4 genotype could have up to a 90 percent chance of developing a chronic illness such as Alzheimer’s.   The Apo E gene occurs as three variations in your body: Apo E 2, Apo E 3, and Apo E 4.  Since genes come in matching pairs, we inherit one from each parent.  There are six possible combinations of Apo E gene pairs: 2/2, 2/3, 3/3, 4/2, 4/3, and 4/4.

The Apo E gene could be a factor affecting how your body uses different types of foods and nutrients and different Apo E genotypes likely process foods differently.  There is an interesting book on this topic called The Apo E Diet.

Over the next few weeks, I will be working to have personal genetic testing done on our entire family and we will find out how our Apo E combinations might play a role in our health.

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