Not the Greatest News for the NPC Community

Well today there was a conference called held by the NIH and NNPDF to update the community on the Cyclodextrin trial.  The news was not what I was hoping for.  They had to put the trial on a pause status due to an infection at the ommaya reservoir site in two patients and another (who is not in this trial) suffered from a brain bleed.  The ommaya reservoir is like a port for a chemo patient but it is surgical placed in the front of the brain.  The infection was cause by bacteria that sits on the skin that causes acne.  At this time they are not sure if NPC patients are at a higher risk since this is a lipids disease or not.  But they knew they couldn't continue with the trial with so many problems and not enough answers.

They put in on hold and got in contact with the FDA who in turn put an official hold on the trial and will send the NIH a letter stating what has to be done to get the trial off the hold status.  The FDA was very pleased with the quick action by the team at the NIH for putting the trial on pause right away without first contacted them.  The NIH will receiver the letter sometime next week and will inform the NPC community once they have a plan of action in place.

Dr. Porter did add that they did collect some promising results from the trial thus far.  The bio-markers looked good and they got goo PK data.  These results where from the patients receiving a very small dose of the cyclodextrin.  Dr. Porter thought they would see nothing with this low of a dose, so that in itself is very hopeful!!

They do think that the infection was not drug related but device related.  So he did go on to say that they will be looking at a lumbar injection as means to administer the drug.  They do have concerns with how much of the drug will actually reach the brain but with the data collected from the trial he believes that they will be able to administer enough of the drug to reach the brain without causing toxicity. 

There is a lot of work ahead for the NIH team but they are committed to get this trial back up and running as soon as they can.  They could not give any kind of time line or dose levels at this time.  I will keep everyone posted as information comes to me.  Please say an extra prayer for the NPC community especially those in the trial that suffered an infection and the child who suffered a brain bleed.  Thank you and God Bless!!

Rare Disease Fight Song

Rally students of Notre Dame, 

Fight rare disease, and sound her fame

Raise her Gold and Blue, 

And cheer with voices true, 

In the fight against rare disease.

Fight rare disease in every game

Strong of heart and true to Notre Dame.

We will ne'er forget her

And we'll cheer her ever,

In the fight against rare disease.

Chorus:

Fight rare disease at Old Notre Dame

Ending their neglect and cheering her name, 

Send the volley cheer on high, 

 Shake all seven thousand down from the sky, 

What though the odds be great or small

Old Notre Dame will win over all, 

While her loyal students march

In the fight against rare disease.

NIH Clinic Trial is a GO!!!

UPDATE: FDA Approves NIH TRND Team for NPC Cyclodextrin Clinical Trial!

Posted: 11 Jan 2013 02:42 PM PST

Dear Families and Friends,

The NNPDF central office received the following update from the National Institute of Health (NIH) NPC Clinic from Dr. Forbes "Denny" Porter.

"We were informed today that the FDA has removed the clinical hold on the hydroxypropyl-β-cyclodextrin trial. We are planning to enroll the first patient in two weeks. This trial is a major step in trying to determine if this is a safe and biochemically effective drug for NPC. Our goal is to use data from this trial to optimize the design of a larger second trial focused on clinical efficacy. Thank you for your help and support!
The TRND Team"

To follow updates and breaking news visit the Cyclodextrin page on the NNPDF web site.

More on the Cyclodextrin Trial

Below you will find the lastest on the Cyclodextrin Trial at the NIH.  Unfortunately Tylor is not a candidate for this first trial because he is on more than one anti-seizure medication.  We will be following this trial closely and we are hopeful that Tylor will be able to participate in the upcoming trial involving Cyclodextrin.

~ November 28th, 2012 ~

        Cyclodextrin (HP-β-CD) for NPC1 Disease

  ~ Clinical Trial Strategy ~

UPDATE ~ November 28th, 2012 ~ UPDATE

Therapeutics for Rare and Neglected Diseases (TRND)

National Institutes of Health ~ Bethesda, MD 

Dear National Niemann-Pick Disease Foundation Family Members,
The latest release pertaining to the upcoming NIH NPC clinical trial has been made available to the NNPDF. To view the NIH NPC Cyclodextrin Clinical Trial Flyer ~ dated: 11/28/12 ~ click here.
This study titled: 2-hydroxypropyl-B-cyclodextrin (HP-B-CD) in Niemann-Pick Disease, type C1, is in the process of being reviewed by the FDA and the team of researchers and physicians associated with the Therapeutics for Rare and Neglected Disease ~ Niemann-Pick Type C Disease Team (TRND NPC Team) at the NIH are hopeful that they will be able to begin enrolling patients in January of 2013.
The National Niemann-Pick Disease Foundation is pleased that we are able to forward this information along to our family membership. The NIH attached flyer specifies that interested parties should note your interest in possible trial participation by e-mailing a representative at the NIH: nichdnpc1@mail.nih.gov
Please note: If you do NOT have access to the internet or an e-mail account please contact the NNPDF Central Offices at the 920-563-0930 and we will assist you in reaching the appropriate contact individual(s) at the NIH for more information.

This is indeed, a very exciting time for all of our NNPDF family community and, more importantly, all of our precious loved ones diagnosed with Niemann-Pick Disease Type C

.

We WILL Persevere in our Quest for a Cure!

Kind Regards, Nadine M. Hill

Executive Director; National Niemann-Pick Disease Foundation

For a historical timeline on the Cyclodextrin (HP-β-CD) for NPC1 Disease Clinical Strategy ~ outlined by the NNPDF ~ please follow the link above.

Road to Discovery, Dean Greg Crawford's Blog

We had the pleasure of meeting Greg Crawford, the Dean of Science at Notre Dame.  He is an awesome man doing a great thing for the NNPDF community.  For the last two years he has biked all over America to raise awareness for NPC and this year he is biking from Boston, MA to Pebble Beach, CA.  He left May 21 and plans on arriving in Pebble Beach June 22....amazing huh?  He will be arriving in time for the Ara Parseghian, a form ND football coach who lost three grandchildren from this disease, golf tournament to raise money for NPC.

He has been blogging about his journey and I thought some of you might what to take a look!!

 ROAD TO DISCOVERY

Day 9: Holiday City, OH, to Notre Dame! 

Today was a terrific day for riding and reaching home for a visit. Peter, a math professor from Notre Dame, and Tom, a friend from Knollwood Country Club, joined us on the sunny, breezy ride from northwestern Ohio.

Read more »



The Ride Schedule

Date	Arriving
5/21/2012	From Boston, MA to Sturbridge, MA (75 miles)
5/22/2012	Lakeville, CT (100 miles)
5/23/2012	Walton, NY (130 miles)
5/24/2012	Corning, NY (125 miles)
5/25/2012	Salamanca NY (105 miles)
5/26/2012	Meadville, PA (100 miles)
5/27/2012	Elyra, OH (100 miles)
5/28/2012	Bowling Green, OH/Montpelier, OH (100 miles)
5/29/2012	Granger, IN (95 miles)
5/30/2012	Matteson, IL (100 miles)
5/31/2012	Mendota, IL (100 miles)
6/1/2012	Davenport, IA (85 miles)
6/2/2012	Oscaloosa, IA (125 miles)
6/3/2012	Creston, IA (110 miles)
6/4/2012	Bellevue, NE (96 miles)
6/5/2012	York, NE (110 miles)
6/6/2012	Holdredge, NE (120 miles)
6/7/2012	McCook, NE (80 miles)
6/8/2012	Yuma, CO (100 miles)
6/9/2012	Byers, CO/Denver,CO (100 miles)
6/10/2012	Denver, CO – ND Club Tour
6/11/2012	Granby, CO (95 miles)
6/12/2012	Craig, CO (120 miles)
6/13/2012	Rangely, CO (90 miles)
6/14/2012	Altamont, UT (95 miles)
6/15/2012	Park City, UT (90 miles)
6/16/2012	Wendover, NV (160 miles)
6/17/2012	Ely, NV (120 miles)
6/18/2012	Fallon, NV (100 miles)
6/19/2012	South Lake Tahoe, NV (100 miles)
6/20/2012	Elk Grove, CA (100 miles)
6/21/2012	Livermore, CA (100 miles)
6/22/2012	Monterey/Pebble Beach CA (100 miles)

A Father speaks about their struggle with NPC

Carl and Emma Burdon, like most parents, want to fill their child's life with as much love as they can.

Every moment with their six-year-old son Calum is particularly precious to the Freckleton couple, though, because he has a rare genetic disorder.

Calum has Niemann-Pick condition (NPC) which is likely to claim his life before he reaches his 10th birthday.

Mr Burdon said: "We have had to accept that unless there is a miracle, Calum is going to die young.

"Children don't usually survive past the age of eight or nine."

Calum was born with an enlarged spleen, one of the symptoms of the condition, but he was almost two when he was diagnosed with Niemann-Pick type C.

'In denial'
The couple were concerned he was not running or jumping about like normal toddlers and doctors did genetic tests on him which confirmed he had the disease in May 2006.

Mr Burdon said it was very difficult to accept. He said: "The hardest thing is the feeling that you can't do anything about it, that gets to you. There's no cure and no treatment and you feel useless."

The family have concentrated their efforts "on squeezing a lifetime of love in whatever time we have with him" and fundraising for children with the disease.

Both singers, the couple have done countless charity gigs for good causes in the past. "It really hits home, though, when you are doing events for your own child."

They stage an annual charity golf day and evening meal at Garstang Golf Club which is being held on 15 July this year and they are aiming to raise £10,000.

The trauma of living with a death sentence hanging over Calum's head has brought the couple closer.

"It's very tough to deal with but we're very committed to Calum and to each other."

Calum Burdon is going to Disneyworld in May through Hopes and Dreams charity His two children from a previous marriage Ricky and Derry, who do not have the condition, are equally supportive.

"They dote on Calum and make a real fuss of him. He always perks up when they're around."

According to the Niemann-Pick Disease Foundation, there are just 500 cases diagnosed worldwide - yet there is another child with the disorder from the Fylde coast.

Nine-year-old Leah Garfitt, the subject of Tuesday night's ITV documentary Leah's Dream, lives less than 20 miles from Calum in Fleetwood.

The two families have formed a bond and Calum and Leah meet up when they go to Brian's House at Trinity Hospice.

As well as support from Brian's House, the family say they also get much needed support from the Niemann-Pick Disease UK.

The charity's executive director, Toni Mathieson, has personal experience of the condition. Three of her children had it.

Now one of the UK's leading authority on the disorder, she said: "Sadly it is always fatal at the moment and it is a very difficult and challenging time for the families of children with the disease. It is never easy."

Mr Burdon glows with pride at his son. "We are so proud of Calum and his achievements but it isn't the usual things you would be proud of your children for - it can be him getting off the couch or finishing a sentence."

A snooker fan, Calum has met his heroes, including a home visit from three-times World Champion John Higgins through his cue doctor Kevin Muncaster who is from Freckleton.

"The look on his face when he realised it was John Higgins was fantastic."

Sports presenter Andy Goldstein has organised it for the couple to take Calum to Disneyworld in May through the Hopes and Dreams charity.

It will be a poignant, though. "We're creating memories for him but we're aware it will probably be his last trip."

Despite the inevitability of his condition, Calum is not short of giving or receiving affection. "I don't know any child who has had as much love and kisses as Calum has."

"He knows he is special, but he just doesn't know why," added Mr Burdon.

NIEMANN-PICK TYPE C FACTS

The disease is inherited. Both parents have to be carriers of the faulty gene and there is a 25% chance that they will pass on the condition to their child

It occurs when the body cannot break down cholesterol and other fats, leading to excessive levels of cholesterol in the liver, spleen and the brain

The condition is characterized by eye movement abnormalities, difficulty in swallowing and slurred, irregular speech, lack of muscle control and intellectual decline leading to dementia

Ara Parseghian Interview with NBC Sports

Ara Parseghian lost three beautiful grandchild from Niemann Pick Type C but he wasn't going to let that stop him. After watching the above video you can see that it helps to keep him fighting for all the other kids with Niemann Pick Disease. The Parseghian's have been instrumental in raising funds for Niemann Pick research. Please watch the video and visit the Parseghian's website.

Researcher move one step closer...

Simple blood test may diagnose deadly Niemann-Pick type C disease

A fatal genetic disorder that frequently takes years to diagnose may soon be detectable with a simple blood test, researchers at Washington University School of Medicine in St. Louis and the National Institutes of Health (NIH) report this week in Science Translational Medicine.

For patients with Niemann-Pick type C (NPC) disease, the test will make it possible to begin treatment earlier, when it is more likely to improve quality of life and to further extend lives.

“NPC is a horrible disease that is easy in its early stages to mistake for other conditions, both because it's so rare and because it has so many different manifestations,” says senior author Daniel S. Ory, MD, professor of medicine and of cell biology and physiology at Washington University School of Medicine in St. Louis. “This is an important step forward both in terms of making a definitive diagnosis much easier and in terms of providing us with a way to quickly assess the effectiveness of experimental treatments.”

There is no U.S.-approved treatment for NPC, which is estimated to affect approximately 1 in 100,000 people worldwide. Miglustat, an inhibitor of complex lipid synthesis, is approved for NPC treatment in Europe, Canada, Russia, Brazil and Taiwan.

Insights from the study may also help scientists better understand health problems in people who are carriers of the disorder, which may include 3 million to 6 million in the United States alone. Having a single mutated copy of the NPC 1 or 2 genes does not cause NPC, but the study's results have led scientists to speculate that it may contribute to heart disease, diabetes and other common illnesses.

“What we learn from studying rare diseases often can be very helpful not only for patients with those rare disorders, but also for efforts to treat much more common conditions,” Ory says.

Ory is co-director of the new Diabetic Cardiovascular Disease Center at Washington University. The interdisciplinary center, which explores the links between diabetes and cardiovascular disease, was established through BioMed 21, a Washington University initiative dedicated to speeding the development of laboratory insights into advances in clinical diagnosis and treatment.

Dr. Ory

NPC typically manifests in childhood with a variety of symptoms including problems walking, slurring of speech and difficulty swallowing. In later stages, it immobilizes patients, causing seizures, dementia and death.

NPC belongs to a class of inherited diseases known as lysosomal storage disorders. The disorder breaks down the cell's normal patterns for handling cholesterol, leading it to accumulate in lysosomes, pockets in the cell that act as garbage disposals. Ory and his colleagues had earlier shown in an NPC mouse model that this causes a buildup in cells of cholesterol that has undergone a chemical change known as oxidation. This change makes the cholesterol more chemically reactive and dangerous to the cells.

Cellular pockets known as lysosomes that have the NPC1 protein appear orange in this photo. Lysosomes that lack the protein, which is mutated in the fatal inherited disorder known as Niemann-Pick type C, are blue because they are full of cholesterol.


Cellular pockets known as lysosomes
that have the NPC1 protein appear orange
in this photo.  Lysosomes that lack the 
protein, which is mutated in the fatal
inherited disorder know as Niemann
Pick Type C, are blue because they
are full of cholesterol. 


To test if these oxidized forms of cholesterol could be used as markers for NPC, Ory collaborated with first author Denny Porter, MD, PhD, an NIH researcher who has assembled one of the largest NPC observational studies. Porter conducts regular health assessments of more than 50 patients with NPC and has amassed a collection of tissue specimens from these patients for purposes of developing new disease markers.

Scientists tested tissue samples in the metabolomics facility of the Diabetic Cardiovascular Disease Center. In NPC patients, two oxidized forms of cholesterol were present at levels nine to 10 times higher than normal. The same markers were not elevated in healthy children and adults or in persons with elevated cholesterol levels, heart disease, diabetes or other forms of lysosomal storage disorders.

“These markers have all the characteristics we wanted for a clinical test, and we're now working to develop it into a clinical assay,” Ory says. “We want to make the possibility of testing for NPC much easier for physicians to consider if they see the slightest hints that it might be present.”

Given the potential advantages that presymptomatic treatment of NPC may offer, including improved quality of life and extended lifespan, Ory also hopes to get people thinking about the possibility of adding NPC to the recommended neonatal screenings.

“We're not sure we fully appreciate the impact of this disease, which may be more common than we think,” he explains. “It could be very helpful to get a better handle on that via neonatal screening.”

Although no group that scientists screened had levels of the two key markers as high as the NPC patients, the markers were significantly increased in parents and siblings of NPC patients. Many of these family members have one mutated NPC gene and are carriers of the disease.

“These markers are indicative of an increased level of stress in cells, and this same kind of stress is seen in many other disorders, including heart disease, diabetes and neurodegenerative disorders such as Alzheimer's disease,” Ory says. “We need further research to confirm this, but it's possible that some of the same damaging mechanisms that take place in NPC patients may be occurring to a lesser degree in persons who only have one mutated copy of an NPC gene and are putting them at increased risk of other disorders.”

If carriers of the disease do have an increased risk of other conditions as a result, new treatments for NPC may also help them, according to Ory.

###

Porter FD, Scherrer DE, Lanier MH, Langmade SJ, Molugu V, Gale SE, Olzeski D, Sidhu R, Dietzen DJ, Fu R, Wassif CA, Yanjanin NM, Marso SP, House J, Vite C, Schaffer JE, Ory DS. Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. Science Translational Medicine 2, 56ra81 (2010).

Funding from the Washington University Specialized Centers of Clinically Oriented Research, the Dana’s Angels Research Trust, the Ara Parseghian Medical Research Foundation and the National Institutes of Health supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.