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

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

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.

Apo E Gene and Diet

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.

Dear British Media – Feel Free To Call or Email!

Dear British Media:

Thank you so much for your interest in our daughters, Addi and Cassi, and their fight against Niemann Pick Type C disease, a fatal cholesterol disorder that is often referred to as the “childhood Alzheimer’s.”  There have been two stories that were written today regarding Addi and Cassi’s cyclodextrin sugar  treatment and we can’t thank you enough for bringing this important health story to the attention of people in the UK.

Unfortunately, there are some incorrect facts in the stories (see below) that are now appearing online.  It also would have been courteous to contact us and conduct fact checking.  We realize that it’s a competitive media environment and you are in a world of meeting daily deadlines but we do not appreciate being quoted in stories when words did not come directly from us. We are more than happy to tell our story to the world (we are trying to do this all the time through our website!) and you can call or email us any time day or night as our contact information is on our website.

Again British media, thank you for getting the word out on Niemann Pick Type C disease.   While considered a “rare disease,” Niemann Pick Type C disease could have implications for millions of people.  The Niemann Pick Type C gene on Chromosome 18 is a very important gene in the human body – we all have this gene and it appears to regulate people’s cholesterol at a cellular level.  We hope that more discoveries regarding the NPC gene will come out soon.

The Evening Standard:

http://www.thisislondon.co.uk/standard/article-23667508-details/The+twins+aged+five+who+suffer+from+Alzheimer+s/article.do

Correct facts:

• Our names are Chris and Hugh Hempel. Chris is Mom, not Dad, as you have reported in your article

• Our children’s names are Addison and Cassidy, we refer to them as Addi and Cassi – no “e’s” at the end of their names

• The US FDA did not give the approval to us today to start these treatments on our children – this was approved a few weeks ago and we are in the process of gearing up for the treatments

• Children’s Hospital of Oakland California is not conducting the actual infusions – mediports for the sugar infusions were surgically installed at this hospital. Cyclodextrin infusions will take place at Renown Regional Medical Center in Reno, Nevada, USA. We are working towards the infusions right now and hope to start in a week or so

• We have no idea if cyclodextrin can help Alzheimer’s patients as was quoted in your story. However, this is an interesting idea and cyclodextrins amazing properties should be looked into further

• Doctors did not discover cyclodextrin, researchers at UT Southwestern University in the United States have reported on cyclodextrins effects in NPC mice

Telegraph:

http://www.telegraph.co.uk/health/healthnews/5055351/World-first-treatment-may-offer-hope-to-twins-with-childhood-Alzheimers..html

Correct facts:

• Niemann Pick Type C does not only impact children, it impacts adults too and there are a number of adult cases in the UK.  Children experience dementia, tangles and other symptoms that are similar symptoms seen in Alzheimer’s disease.  Possibly the two diseases are related to disruptions in lysosomal function in the cell?  Why are Alzheimer’s researchers not looking more at NPC and Lysosomal Storage diseases??

• The proper spelling for the disease is Niemann Pick Type C, not Niemann Pick’s

• Did you find quotes from Chris from previous videos on our website?  Feel free to contact us and we will be happy to give direct quotes that are current

• This is not the world’s first treatment – we actually provided all of the cyclodextrin information we submitted to the US FDA to a family in India and Lebanon. Cyclodextin infusions have been started on two children in these countries based on our ground work.  Due to the fact that these countries do not have the same types of restrictions that we have in the United States, these families have been able to start over 1 month ago!  This will be the first time in the US this will be tried

Again, thank you for starting the education process on Niemann Pick Type C disease.   Please pray for all who have this horrible and devastating illness that is stealing their minds.

President Obama, Please Meet Addi and Cassi To Understand Why Your Jay Leno Joke Is No Laughing Matter

President Obama’s Special Olympics joke on Jay Leno may not seem like a big deal to some Americans but for others the gaffe is disappointing. Our twins, Addi and Cassi, are afflicted with a rare and fatal cholesterol disease called Niemann Pick Type C and they are considered “special needs.” We have all made mistakes with words or put our foot in our mouth from time to time. President Obama is human too and must be forgiven by the special needs community for his off hand joke. Of all people, our President understands what it’s like to live in a society where stereotypes abound and hopefully he will turn this negative situation into a positive.

What’s frustrating to me is that all special needs children seem to get lumped into one category — “retarded” (a word that should be forever removed from our vocabulary). Children with Ataxia-Telangiectasia are born healthy but completely lose their entire motor coordination control center in the cerebellum.  Their minds remain intact but they progress to wheelchairs and often die in their teens. Someone on the street would think a child with A-T is intellectually challenged when they are not. Many children who fit into the special needs category have life threatening and debilitating diseases like Addi and Cassi – they are called Rare Diseases.

Millions of people, primarily children, are afflicted with Rare Diseases that are often genetic in origin. President Obama needs to educate himself quickly and learn what it truly means to be special in America.  He will then learn to laugh with us and not at us. More importantly, President Obama can not only help us overcome stereotypes but he can invest in much needed medical research that can keep our special kids alive.

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