Sunday, November 19, 2017

FDA Approves Request For New Cyclodextrin Treatment For Niemann Pick Type C

September 25, 2010 by  
Filed under Cyclodextrin, Featured Content


Cyclodextrin Infusion bottles - We'll now mix cyclodextrin in saline and put smaller amount into Addi and Cassi's Central Nervous System to bypass the blood brain barrier


FDA Approval Received!

Children’s Hospital Oakland Receives FDA Clearance to Begin World’s First Cyclodextrin Administration Into the Brains of Twins with Rare and Deadly Cholesterol Disease

Sugar Molecule Used In Common Food and Household Products Like Febreze® Fabric Refresher Called Hydroxypropyl Beta Cyclodextrin (HPßCD) Will be Delivered into Twins’ Central Nervous System in an Attempt to Stop Neurological Progression of Niemann Pick Type C Disease

September 23, 2010 – Oakland, Calif. – Children’s Hospital & Research Center Oakland announced today that the US Food and Drug Administration (FDA) has granted clearance of an Investigational New Drug (IND) application to introduce Trappsol® Cyclo™ (Hydroxypropyl Beta Cyclodextrin or HPßCD) into the brains of six year old identical twin girls dying of a rare brain-destroying cholesterol disease called Niemann Pick Type C (NPC). Known as “childhood Alzheimer’s,” NPC is a deadly progressive neurological condition that causes severe dementia and other debilitating symptoms in children. The FDAs approved use of Trappsol® Cyclo™ marks the first time in medical history that HPßCD will be delivered directly into the brain of a human being in an attempt to arrest a progressive and fatal neurological condition.

Within days, Addison and Cassidy Hempel will travel from their home in Reno, Nev., to Children’s Hospital Oakland to start ongoing injections of Hydroxypropyl Beta Cyclodextrin (HPßCD) into their central nervous systems. Initially, the twins will receive six cyclodextrin treatments of Trappsol® Cyclo™ via lumbar injection over a 12-week period. If Trappsol® Cyclo™ is well tolerated and no adverse side effects occur, the twins are then expected to undergo brain surgery to implant access ports allowing HPßCD to be delivered into the brain’s ventricle system.

HPßCD is a ring of seven sugar molecules known as a cyclic oligosaccharide that is derived from starch. Derivatized cyclodextrins are used extensively in research labs to remove cholesterol from cultured cells and are well known in the pharmaceutical industry for their ability to solubilize drugs. Underivatized cyclodextrins are used throughout the food industry to make cholesterol-free products, such as fat-free butter, eggs and milk products. HPßCD is recognized as a GRAS (Generally Recognized As Safe) material for use in food products in Asian and European countries and is being considered for similar certification in the United States. Hydroxypropyl Beta Cyclodextrin, the chemical compound that will be administered into the twins’ central nervous system, is also an active ingredient found in Procter & Gamble’s Febreze® Fabric Refresher and is used to help eliminate odors from fabrics. Millions of people worldwide are exposed to small amounts of cyclodextrin compounds every day in food, cosmetics and household products.

“It is remarkable to be in position to try a genuine medical intervention that may retard or restore neurological function in children suffering from Niemann Pick Type C disease,” said Caroline Hastings, MD, the Children’s Hospital Oakland pediatric hematologist/oncologist who diagnosed the twins. Dr. Hastings also manages the satellite hematology/oncology clinic at Renown Regional Medical Center in Reno where the girls receive much of their treatment. “This family’s tremendous courage to move forward with this groundbreaking treatment to deliver cyclodextrin into the brains of their twins provides real hope for all children afflicted by this mind-robbing condition and possibly others suffering from cholesterol and lipid related disorders.”

In April 2009, the FDA approved an Investigational New Drug protocol that allowed Addison and Cassidy Hempel to undergo weekly intravenous infusions of Hydroxypropyl Beta Cyclodextrin into their bloodstreams through a Medi-Port catheter implanted in their chest walls. However, research conducted by David Begley, PhD, a leading blood-brain barrier expert at Kings College London, discovered that Hydroxypropyl Beta Cyclodextrin does not cross from the bloodstream into the brain. While the Hempel twins have shown improvements with ataxia and have less difficulty swallowing following intravenous intervention with HPßCD, they continue to decline neurologically and there are no other treatment options available to save their lives. The twins have lost most of their ability to speak and are experiencing intermittent seizures and dementia; however, the girls can still walk, see, and communicate to their parents with a range of sounds and gestures.

On June 13, 2010, Dr. Hastings filed a revised protocol to the Hempel twins’ Investigational New Drug applications with the FDA requesting permission to deliver Trappsol® Cyclo™ directly into the central nervous system of the twins in order to bypass the blood-brain barrier. Researchers studying Niemann Pick Type C afflicted cats and mice have discovered that when HPßCD is delivered directly into the brains of these animals, HPßCD has a remarkable life extending effect and appears to arrest the progression of this deadly neurological condition. It is currently unknown exactly how HPßCD is working to achieve these astonishing neurological effects in NPC animals or if it will have the same effect in humans.

For Chris Hempel, mother of the twins, the start of cyclodextrin treatments into the central nervous system of her twins “creates new hope that was unimaginable even a few years ago for an ultra rare disease with a certain death sentence.” Since receiving the NPC diagnosis in October 2007, Ms. Hempel has worked tirelessly with doctors and researchers around the world to search for a lifesaving treatment for her twin daughters. In May 2010, she worked with Dr. Hastings to receive one of the few orphan drug designations granted by the FDA for the compound Trappsol® Cyclo™.

“It’s extraordinary to think that a sugar compound used in common products found in my refrigerator and laundry room could have such a profound effect on human cholesterol metabolism and may actually save our daughters lives,” said Hempel. “We are incredibly grateful for the support we have received from the medical, regulatory, pharmaceutical, and academic communities who have worked to help us bridge the scientific gap and turn a treatment idea into a treatment reality.”

Approximately 500 children worldwide have been diagnosed with double genetic mutations on the Niemann Pick Type C cholesterol gene, yet what scientists learn about these children may have implications that reach far beyond this ultra rare genetic cholesterol disease. Recent published research reports of the role for the NPC1 gene in Alzheimer’s disease and human immunodeficiency virus infection (HIV) make Niemann Pick Type C disease and gene research relevant to millions of people worldwide.

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Cyclodextrins – Recipes To Make Edible Nanostructures and CD MOFs To LifeSaving Drug Treatments

September 6, 2010 by  
Filed under Cyclodextrin

Kenneth Chang of the New York Times reports on researchers creating edible nanostructures with gamma cyclodextrin which researchers are calling edible CD MOF (metal-organic frameworks). Of course, another amazing discovery with cyclodextrin that was found by accident!

Potential applications with this gamma cyclodextrin (CD MOF) could include storing hydrogen in future fuel cells in cars. Interestingly, the article mentioned “drug delivery” which I am already working on with hydroxy propel beta cyclodextrin (Trappsol brand). I wonder if HPBCD could be turned into nanoparticles and cross the blood brain barrier? I wonder if this new gamma cyclodextrin nanoparticle crosses the blood brain barrier?

One of the articles quotes a researcher who made the discovery as saying, “With our accidental discovery, chemistry in the kitchen has taken on a whole new meaning!”  This statement is something I can relate to as I’ve mixed up cyclodextrin into juice and with curcumin to try and get better absorption.

The article also gives a ‘recipe” on how to make edible cyclodextrin nanostructures which I found interesting. We have our own cyclodextin recipe that I am hoping the United States Food and Drug Administration will approve within the next few weeks.  Our doctor is trying to use cyclodextrin to save the lives of my identical twin six year old girls who suffer from Niemann Pick Type C, a rare and fatal genetic cholesterol disease that causes dementia in children.

When cyclodextrin is given intrathecally into cats and mice suffering from Niemann Pick Type C disease, hydroxy propel beta cyclodextrin arrests the neurological progression of the disease! When was the last time you heard of a compound or drug arresting the neurological progression of a disease like Alzheimer’s, Parkinson’s or ALS?

Here is the simple recipe we have proposed to the FDA:

Cyclodextrin To Stop Brain Neurodegeneration In Fatal Cholesterol Disorder

1. Dissolve 175 mg of hydroxy propel beta cyclodextrin (Trappsol brand) into 6 ml sterile saline

2. Put into sterile tube

3.  Inject via lumbar puncture into central nervous system

4. Repeat with dose escalations by adding 17.5 mg of HPBCD every two weeks until concentrations of 5 mM are achieved

5. Test central spinal fluid for reductions in A-beta levels, total T-Tau levels and other biomarkers such as the oxysterol called 7 ketocholesterol

6. Conduct neurological assessments on twins to see if speech returns, seizures and gelastic cataplexy reduce, etc.

7. For complete FDA filing with full instructions, contact me: chris@hempelfamily.com

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Vote 4 Hope at Pepsi Refresh To Find Cures for Rare Skin Conditions like Epidermolysis Bullosa, Harlequin Ichthyosis, Xeroderma-Pigmentosum

September 2, 2010 by  
Filed under Videos

During the Vote4Hope Pepsi Refresh Rare Disease Campaign, I am making video postings throughout September to raise awareness for all rare diseases, not simply the horrific disease called Niemann Pick Type C that my six year old identical twins suffer from.

Today’s videos are some of the most heartwrenching videos I have ever watched. The videos are of  a boy named Garrett who suffers from Epidermolysis Bullosa, or EB, a rare genetic skin disorder the the majority of people have never heard of, yet it apparently affects 100,000 children across the United States to various degrees.

Children born with Epidermolysis Bullosa lack the ability to produce the collagen-7 protein that acts as a glue to bind the inner and out layers of skin together. Garrett, “The Boy Beneath the Bandages” videos won the 2010 Rare Disease Day video contest.

This video is a true life view of what living day-to-day is like with a rare debilitating skin disease.

Please VOTE everyday at Pepsi Refresh for the Global Genes Project to win $250K so we can continue efforts to help the entire rare disease community.  Join the Rare Disease team on Facebook.

Check out why I am taking time the entire month of September to get the word out for  rare diseases such Epidermolysis Bullosa and read the  press release to learn more about the lack of treatments and cures for millions of people.

There are a number of other rare skin conditions such as:

  • Harlequin Ichthyosis – This is an extremely rare skin disease, caused due to a defect in ABCA12 gene. This disease is present at the birth itself. It is characterized by dry, scaly skin, which sheds 7 to 10 times faster than normal skin. The body is covered with fish like scales, which also have a hair growth on them. The scales are extremely hard and give the skin an armor like appearance. Herlequin ichthyosis is one of the rare skin disorders in children, which kills them within a few days of birth
  • Sweets Syndrome or Neutrophilic Dermatosis – This condition is a result of hypersensitive response of the skin to allergens. The skin tends to develop plaques all over the body, in presence of the allergen. Fever and pain are the accompanying factors, along with skin rash.
  • Morgellons Disease – This is yet another rare skin disease with an unknown cause. The condition is characterized by itching, crawling, biting sensation, underneath the skin
  • Argyria – Argyria is a cosmetic skin disorder which occurs due to excessive consumption of silver
  • Xeroderma-Pigmentosum – Xeroderma pigmentosum is a genetic disorder caused due to alteration of genes, responsible for normal DNA repair. As a result, the damage due to UV rays of the sunlight cannot be repaired. This leads to redness and itching of the skin, after sun exposure.
  • Urticaria – Urticaria is an allergic response to sunlight, food, stress, water etc.


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Pepsi Refresh Links For Vote4Hope, Vote 4 Hope Rare Disease Campaign

September 2, 2010 by  
Filed under Featured Stories

If you are looking for information on the Pepsi Refresh Vote4Hope Rare Disease campaign being run by the Children’s Rare Disease Network and Global Genes Project, here are the links and information you need to help fund hope for sick kids.

Click here for Pepsi Refresh Site Link – actual URL if you need it is:  http://www.refresheverything.com/fundhopeforsickkids



Text To Vote: Text to 73774 (Pepsi), followed by our voting code (102614) in the text message. You will then receive a confirmation text.

Click here for Facebook Vote4Hope Team: actual URL for Facebook is http://www.facebook.com/ivote4hope

Click here for Vote4Hope.org and meet our Rare Disease Kids Who Are ‘Ambassadors of Hope’ -  URL if you need it is: http://www.vote4hope.org/

Click here for Press Release about Pepsi Refresh Vote 4 Hope Rare Disease campaign.  Actual press release link if you need it is: http://www.prnewswire.com/news-releases/the-global-genes-project-aims-to-battle-rare-disease-through-the-vote4hope-campaign-and-pepsi-refresh-competition-101956358.html

Click here for Vote4Hope Ambassador or Angel badges – link if you need it is: http://204.42.150.181/vote-4-hope-widgets-and-badges/


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Gleevec Cancer Drug Reported To Work In Alzheimer’s disease also working in Niemann Pick Type C mouse

September 2, 2010 by  
Filed under Featured Stories

A New York Times story is reporting that Paul Greengard (and his dog Alpha), who won a Nobel Prize for his work on signaling in brain cells, has found that the cancer drug Gleevec, is a new potential drug target for Alzheimer’s disease and blocks gamma secretase activating protein. Rudolph Tanzi and Paul Aisen are quoted in the article.

I think they would all be very interested to know that Gleevec is also working in Niemann Pick Type C mice and kids afflicted with this ultra rare condition are doing small personal trials with the drug.

Niemann Pick Type C disease is an ultra rare and fatal genetic cholesterol disorder caused by a double mutation on the NPC1 or NPC2 gene.  The disease is progressive neurological condition that causes dementia in children and is often referred to as the “childhood Alzheimer’s.”

Last year, in a comprehensive  drug screen conducted by Dr. Christopher Austin’s group at the National Chemical Genomics Center (NCGC), Gleevec showed up as a drug target for Niemann Pick Type C disease.

Dr. Brian Druker, an oncologist who revolutionized the treatment of cancer through research to develop Gleevec, is working with The Hadley Family in Medford, Oregon, who have two children suffering from Niemann Pick Type C disease. Novartis has offered to sponsor Gleevec for both of their children for a six month trial which is now underway. Children suffering from Niemann Pick Type C disease in Brazil are also taking Gleevec without any side effects.

Gleevec (also called Imatinib) has been studied by Dr. Silvana Zanlungo and Dr. Alejandra Alvarez of the Pontifica Universidad Catolica de Chile, and the results of their studies have indicated positive benefits in weight gain, strength and coordination in Niemann Pick Type C mice.  See the abstract: http://www.fasebj.org/cgi/content/full/22/10/3617 .  But only a very small amount of Gleevec crosses the blood brain barrier when given orally.  Imagine if you can do intrathecal?

There is also some evidence in the literature showing Imatinib effects on insulin resistance.  My twins have hypometabolism spreading throughout their brains and their PET scans show the pattern is very similar to early onset Alzheimer’s.

The Chile group has explored the relationship between Niemann Pick Type C neurodegeneration and the activation of the apoptotic system c-Abl/p73.  This system is formed by the c-Abl tyrosine kinase and p73 pro-apoptotic transcription factor. Both c-Abl and p73 proteins are expressed in the cerebellum, the brain region that is most affected in Niemann Pick Type C.

The Hadley’s have been leading the charge on getting Gleevec studies underway in Niemann Pick Type C mice. They have also been looking at Nilotinib, a tyrosine kinase inhibitor used for treatment of leukemia and other cancers.  However, Imatinib (Gleevec) I believe is working better in the mouse studies.

More and more scientific reports are coming out showing the relationship between Alzheimer’s disease and Niemann Pick Type C disease so I am not surprised that Gleevec could be a drug target in both conditions.

Dr. Kaj Blennow, a leading Alzheimer’s research in Sweden, has found Amyloid beta release is increased in Niemann Pick Type C. They are working on studies around γ-secretase and β-secretase and have found some data showing lipid accumulation affects Aβ metabolism. Amyloid metabolism in Niemann Pick Type C may be caused either by the impaired vesicular trafficking in NPC or by direct modulation by lipid alterations on amyloid processing enzymes (ie. gamma-secretase).

Another recent study by Alzheimer’s researcher Katarina Kågedal shows increased expression of the lysosomal cholesterol transporter NPC1 in Alzheimer’s disease.  The study measured NPC1 mRNA and protein expression in three distinct regions of the human brain, and it was found that NPC1 expression is upregulated at both mRNA and protein levels in the hippocampus and frontal cortex of AD patients compared to control individuals.

Further, Ralph Nixon’s work shows that Alzheimer’s might have a lysosomal storage component like Niemann Pick Type C disease.

Intrathecal Gleevec – this is an interesting idea!  Since we are pursuing intrathecal cyclodextrin treatment on the twins, intrathecal Gleevec treatment might also be another potential avenue we could explore.





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