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

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.
Source: http://addiandcassi.com/fda-approves-request-cyclodextrin-treatment-niemann-pick-type/

Zavesca/Miglustat update from US FDA Panel shows some hope for Australia

UPDATE 2-US FDA panel backs new use for Actelion drug
Tue Jan 12, 2010 5:31pm

Stocks Regulatory News Healthcare
* FDA decision due by March 10
* Agency usually follows panel recommendations (Adds panelist, company comments)
By Lisa Richwine
SILVER SPRING, Md., Jan 12 (Reuters) - A U.S. advisory panel on Tuesday recommended approval of an Actelion Ltd (ATLN.VX) drug for treating a rare disease that often kills patients in their teens after fats accumulate in their organs.
A Food and Drug Administration advisory panel voted 10-3 to recommend approval of Actelion's Zavesca pill for patients with a condition called Niemann-Pick type C disease (NP-C).
Europe's largest biotech company already sells Zavesca in the United States for another rare disorder, type 1 Gaucher disease.
Panel members who supported the drug said there were signs Zavesca would help patients with NP-C even though the drug failed to meet the main effectiveness goal in a company study.
"The risk from the drug is not devastating, but the disease is devastating. I think patients deserve an opportunity to see if they can benefit," Katherine Flegal, a senior research scientist at the Centers for Disease Control and Prevention, said.
Actelion is trying to cut its dependence on Tracleer, a drug that treats a rare heart and lung disorder and brings in more than $1 billion a year. Zavesca sales through the first nine months of 2009 were 38.3 million Swiss francs ($37 million).
Doctors can prescribe Zavesca now for NP-C, but Actelion needs FDA clearance to market the drug specifically for that use. Patient advocates also said insurers are reluctant to pay for the drug for NP-C patients without the approval. The drug costs $159,000 a year per patient.
NP-C, which has no approved treatment in the United States, causes cholesterol and other fats to collect in the brain and various organs. That leads to impaired brain function, lack of muscle control, slurred speech and eventually death. Symptoms usually develop around age 10, and most patients die within five to 10 years of diagnosis.
Just 500 patients worldwide are known to have the disease, including about 200 in the United States, Actelion said.
Zavesca, or miglustat, was designed to block the action of an enzyme involved in producing the fats that cause problems in NP-C.
But the drug failed to meet the main goal in a 29-patient study comparing it to a placebo on measurements of eye movements that Actelion said were a sign of the disease's progression.
The company argued that other findings from surveys of NP-C patients who had been treated with Zavesca showed the drug slowed or stabilized problems with swallowing, walking and speaking.
That type of data is considered less reliable than findings from clinical trials. Actelion, however, said the improvements showed the drug was working because NP-C patients without treatment will get worse over time.
"This is a relentlessly progressive disease," Dr. Isaac Kobrin, Actelion's chief medical officer, told the panel.
"We clearly see a change in the progression rate (with Zavesca). It's a very clear signal," he said.
Actelion said risks such as diarrhea were manageable and outweighed by benefits. FDA reviewers said some NP-C patients had reduced growth and lower levels of blood platelets. Actelion said it would urge monitoring of those issues.
The FDA usually follows panel recommendations when deciding whether to approve medicines. A decision is due by March 10.

Curcumin supplement

The “Real Curcumin” for Treating Alzheimer’s, Parkinson’s and Other Brain Diseases

Verdure Sciences — Never heard of this company? Neither had I until I started trying to find a natural botanical compound called Curcumin to help treat Addi and Cassi, our identical twins who suffer from a fatal disease that mimics Alzheimer’s in young children. It’s called Niemann Pick Type C (NP-C) and I learned last October that it’s trying to destroy my twins’ brains and kill them.

There is only one experimental drug for Niemann Pick Type C that costs a whopping $160,000 per year so I began looking at every available alternative to treat our twins and save them from dementia. After learning through a special MRI brain scan that Addi and Cassi have brain inflammation I focused my efforts on anti-inflammatory products that get across the blood brain barrier.

I had heard about a natural “wonder compound” called Curcumin that was working well in NPC mice studies and also in Alzheimer’s mice studies. Curcumin is not a new idea. It’s a component of Turmeric, an Indian spice, and people have been trying it as therapy for a variety of diseases and there are thousands of scientific papers on its amazing properties. But I found out there was a major problem with Curcumin. The BBB.

Curcumin was a “lab superstar” and working well in test tubes but when tested in humans the absorption rate was extremely low. I was told by our doctors that the Curcumin currently available on the market, even pharmaceutical grade, would not cross the blood brain barrier (BBB) to help Addi and Cassi with brain inflammation. I decided I would try and create my own “bio-available” version of Curcumin and started reading everything I could get my hands on. I even arranged for a formulation pharmacy to help me make a Curcumin suspension. It was then that I read about Dr. Greg Cole.

Dr. Cole is a leading Alzheimer’s researcher at UCLA and during my research I found out that he is the leading authority on Curcumin and had written dozens of papers on the neuro-protective properties of the substance. I decided to email him to see if he could help me understand the bio-available aspects of Curcumin.

A prayer was answered the day I emailed Dr. Cole. His team at UCLA has developed a formulation of “Optimized Curcumin” that works more like a drug with “super bio-availability.” See the chart. UCLA’s Curcumin was not only crossing into the blood stream it was crossing through the blood brain barrier (BBB). The BBB is a membranic structure in the central nervous system (CNS) that restricts the passage of various chemical substances and things like bacteria between the bloodstream and the neural tissue itself, while still allowing the passage of substances like oxygen that is essential to metabolic function.

UCLA put me in touch with Verdure Sciences, an innovative bio-nutritional company, making the super bio-available version of Curcumin. UCLA and Verdure Sciences have done extensive testing and spent several years creating this special formulation. I immediately put Addi and Cassi on significant doses of Curcumin and noticed improvements in their mood, balance and coordination right away. While this is anecdotal, I cannot attribute these positive effects in my girls to anything other than Verdure Sciences optimized Curcumin formulation. Except for a modest amount of diarrhea when we initially started the girls on it, there are no negative side effects from what I can tell. It’s all natural and not even a drug yet it’s acting like a powerful anti-inflammatory.

Do not be fooled by what other companies claim with their Curcumin products. If they tell you it’s optimized Curcumin, it’s not! There are lots of Internet scams and companies that make all kids of false claims. Verdure Sciences is the only company that has the optimized Curcumin with UCLA mice studies to back it up. The product is going to be marketed under the name LongVida or “Long Life” but right now it’s only available if you call them directly.

One of the real neuro-protective compounds for the 21st century has finally arrived and it’s not even made by a pharmaceutical company. Thank you UCLA and Verdure Sciences for persevering to bring theraputic Curcumin to people. While the drug companies are only interested in “drugs” and financial profits, you have shown us a new pathway with Curcumin that is not all about money — it’s truly about health and trying to save peoples lives. I will be forever grateful and I know others will be too.

Source: http://addiandcassi.com/year/the-real-curcumin-for-treating-alzheimer%e2%80%99s-parkinson%e2%80%99s-and-other-brain-disease