Dementia in Children and Teens – When Kids Brains Regress Like The Elderly

The Alzheimer’s Society and Alzheimer’s Association have lots of information on caring for people with dementia but no resources on their website for people caring for children, teens and young adults suffering from dementia. There are many kids who have dementia as a result of rare diseases even though most people think dementia strikes the elderly.

I know it’s hard to believe that six year old kids like Addi and Cassi have dementia but they do.  It can be very difficult to deal with dementia in children as they don’t remember (or can’t learn) that burners are hot, stairs are steep or cars come up and down the street.  Addi and Cassi were once potty trained and knew their nursery rhymes but then forgot what they learned as a result of their fatal genetic cholesterol condition that is destroying their brains.

As you can imagine, the thought of your children forgetting who you are is very distressing to parents.  There is a lot of grief and sadness and yet little support to deal with your kids losing their minds.

Here are some conditions in children that involve dementia:

• Adrenoleukodystrophy
• Alexander disease
• Autism (Infantile)
• Batten disease
• Canavan disease
• Juvenile Huntington’s disease
• Metabolic diseases
• Niemann-Pick Type C
• Subacute-sclerosing Panencephalitis (SSPE)
• Tay Sachs disease

The Niemann Pick Disease Group in the UK has written a guide to help parents, teachers and care professionals understand dementia in young people.  But we need more resources written and more educational efforts to bring attention to dementia in the young.  For example, how can school children cope with having a classmate who has a dementing disease like Niemann Pick Type C. Niemann Pick Type C children do have best friends that they may not remember in the future as their fatal condition progresses.

I am going to contact the Alzheimer’s Foundations to see if they are willing write a story about kids and dementia. Maybe if people knew this was happening to children they would care more about dementia or give more to dementia research.

Guidelines To Write and Submit an Orphan Drug Application For A Rare Disease

While working on our orphan drug application for Cyclodextrin for the treatment of Niemann Pick Type C disease, I searched the Internet looking for examples of an actual orphan drug application that was filed with the U.S. Food and Drug Administration.

Not surprisingly, I could not find any ‘real applications’ that could be used as a reference or starting point. Since most applications are filed by Pharma or BioTech companies, the applications are typically kept confidential.

Here is a PDF document of the actual orphan drug application we filed with the FDA a few weeks ago (it takes a minute to download as the PDF is large). I hope that the posting of our completed application will benefit someone else who is going through the application process and is not sure where to start.

Dr. Timothy Cote stressed at the FDA Orphan Drug Workshop at Keck Graduate Institute that too many companies over complicate the process and file volumes of data when it’s not really necessary. Making a request for orphan drug designation is a  simple process and the application can be 10 or so pages with backup material.

Things To Consider Before Filing Orphan Drug Application

Here are some key things I learned at the FDA Workshop on how to file for a request for orphan designation (RFD):

• In 2009, 250 requests for orphan drug designation were filed with the FDA, and 160 received it.  According to the FDA, roughly 60-70% of applications result in granting of orphan status
• Denials were generally as a result of not meeting rare disease prevalence requirements (ie. trying to submit for something that is not a rare disease or a subset of a larger disease)
• Here is what you will need to be prepared to answer in your filing:
  • What is the disease and is the disease rare (less than 200,000 prevalence)?
  • Will your drug treat this rare disease?
  • Can you demonstrate that there is “promise” that the drug will be effective in treating the rare disease. According to the FDA, “promise” is liberally interpreted to include:
    • Data from clinical trials OR
    • Data from case studies/reports OR
    • Data from animal models OR (rarely)
    • Data from in vitro experiments
    • Theories are NOT accepted

• Expect roughly 60 days to get a decision once you make a filing
• A negative decision can always be overturned.  The record remains forever open according to Dr. Cote
• If you receive a designation, you need to file an annual report each year to give an update on your progress. You can now file a single annual report with the FDA and EMA.  If we receive a designation for Cyclodextrin, I will write a separate blog on other requirements we will need to fulfill

Suggested Reference Materials

Here is some suggested reference materials that the FDA uses to guide people who call the FDA with questions on creating requests for orphan designations (RFD).

• Code of Federal Regulation 21 CFR 316
• 21 CFR 316 Jan 1991 Preamble to proposed legislation – This document provides the Agency’s thinking about Orphan drug development regulation
• Orphan Drug Act
• Do a Designation Notes (word document)
• Rare Disease Prevalence data
• Tips for submitting a Request for Designation (RDF)
• How to apply for Designation as an Orphan Product – For Industry
• European Medicines Agency documents

Dr. Cote told the group that the FDA’s Office of Orphan Products Development is there to help people with the process. I have had many dealings now with the staff at the FDA and they have been extremely helpful.

FDAs Orphan Drug Workshop Featured in Wall Street Journal – Push To Cure Rare Diseases

Below is a story that ran in today’s Wall Street Journal (Page A 3) on the FDA workshop I attended a few week ago at the Keck Graduate Institute in Claremont, CA.  We filed an orphan drug application for Cyclodextrin for the treatment of Niemann Pick Type C disease, an ultra rare cholesterol disease that afflicts our twins Addi and Cassi.

Amy Dockser Marcus, Pulitzer Prize winning health reporter, was at the FDA workshop and wrote a story about our filing which accompanies the main story on the FDAs Workshop for Orphan Diseases.  Thanks to Amy and the Wall Street Journal for giving Rare Diseases the attention they deserve!

The story in currently running online on the front page of the Wall Street Journal’s website.

At an FDA Workshop, a Mom Looks for Help

By AMY DOCKSER MARCUS

CLAREMONT, Calif.—Among the 14 groups at the Food and Drug Administration workshop that filed applications for orphan drug designation, Chris Hempel—part of a small team—stood out in her long-sleeved T-shirt and jeans.

The corporate potential applicants at the event tended to guard their own anonymity, but many couldn’t help ask Ms. Hempel who she was. “I’m a mom,” she replied. The FDA doesn’t require an applicant for orphan drug designation to be able to run a trial or make the drug, or even be a researcher.

Ms. Hempel attended the Feb. 25-26 FDA workshop along with Ron Browne, a scientist hired by a group of families with children who have a fatal cholesterol metabolism disorder known as Niemann-Pick Type C (NPC). In patients with NPC, cholesterol builds up in the tissues, leading to neurological decline and death, often before the age of 20. There is no cure. The families are kicking in around $700,000 a year to fund research into treatments.

Ms. Hempel sought orphan drug designation for a form of a compound called cyclodextrin. As The Wall Street Journal reported in April, Ms. Hempel received FDA permission to give experimental cyclodextrin infusions to her twin 6-year-old daughters, Addison and Cassidy, who have NPC. Ms. Hempel said since they started the infusions their swallowing and awareness has improved and they have had no side effects. It isn’t yet known whether the drug is doing that or if it is slowing down progression of the disease.

The Reno, Nev., mom says she hopes a designation could attract drug-company interest and put the parents in a better position to apply for FDA grants to conduct further research. Ms. Hempel asked Caroline Hastings, an oncologist who is the twins’ supervising doctor on the cyclodextrin infusions at Children’s Hospital & Research Center Oakland, to sponsor the application in hopes of being taken more seriously.

Ms. Hempel made it clear that she was there as a patient advocate. She had a hot-pink binder—her daughters’ favorite color—in which to file the application and documents. At the meetings with the FDA staffer, Ms. Hempel and Dr. Browne picked up an important tip: They were missing a required document—a cover letter written to Timothy Coté, director of the FDA’s Office of Orphan Products Development, and signed by the sponsor, Dr. Hastings. Ms. Hempel hastily tracked down the doctor and got her to FedEx a signed cover page.

Ms. Hempel won’t know for 60 days if the designation is approved but says the FDA staffer told her the application looked “solid.” She says the workshop helped “demystify the process.”

Write to Amy Dockser Marcus at amy.marcus@wsj.com

FDA Does Not Approve Actelion’s Zavesca in US – Distressing News For Niemann Pick Type C Community

Actelion, the makers of Zavesca, today put out a brief statement saying that the U.S. Food and Drug Administration did not approve Zavesca and wants more information from the company on treating Niemann Pick Type C, a rare and dementing neurological disease that afflicts our six year old identical twins, Addi and Cassi.

Niemann Pick Type C disease is caused by the inability of the body to process cholesterol at the cellular level and as a result severely destroys the brain and organs like the spleen and liver.

The FDA is asking Actelion for more pre-clinical and clinical information on Zavesca before it will approve the drug.  The drug has been approved in the European Union, South Korea, Brazil, Russia, Australia and Canada for adult and pediatric patients with Niemann Pick Type C disease.

I hope Actelion will continue to press forward and make the investment in Niemann Pick Type C disease after coming this far.

This is surely a setback for our entire community as many people have worked for years to push this drug forward and were hoping for FDA approval. Addi and Cassi have been taking Zavesca for two+ years and many NPC kids are showing moderate improvements. It would be devastating if we could not have our twins on this drug when data shows it provides a benefit.

This is a lesson learned for me. Now that I am pursuing Cyclodextrin as a treatment for Niemann Pick Type C disease, I need find out exactly what the FDA is looking for in the way of pre-clinical data. I want to make sure that the data we are gathering on Addi and Cassi’s today will be useful in the future.

I would like to understand what thee FDAs top five measurements of success are and what it takes to get a drug approved for an ultra rare disease that afflicts so few. I don’t want to get in front of an FDA panel five years from now only to be told we did not collect adequate pre-clincal and clinical data.

Obama Cracks Jokes About Cholesterol Level And Personal Health – Is He Out of Touch?

I almost had a heart attack today (no pun intended) when I read that President Obama was joking about his cholesterol.  “I don’t want any lectures about my cholesterol,” he said, according to the pool report.

If President Obama needs inspiration to cut his cholesterol and push away that fried chicken the next time he sits down for a meal, he might want to read about my six year old identical twins and their cholesterol problem. Cholesterol is killing them. And it’s no joke!

If President Obama was to meet my twins he might ask them why he should pay attention to his cholesterol and how cholesterol impacts their health.  Too bad cholesterol has destroyed their ability to talk and their memories too. My children suffer from one of the worst genetic cholesterol diseases on the planet – Niemann Pick Type C. Millions of other people are suffering from cholesterol related illnesses that kill – just ask former President Clinton or the people on statin drugs.

I think President Obama should call the American Heart Association and apologize.  We need people in the highest levels of our government taking their personal health seriously and using their time in the public eye to educate.  How can you expect a nation to change their eating habits when you’re stuffing fried chicken in your mouth and cracking jokes about your health?  The PR people should be fired as Obama should know exactly what he should say to the public about his cholesterol and meals for him should be ordered in advance.

One of the last jokes Obama cracked was on Jay Leno about the Special Olympics and I wrote a blog about this too. I’d like the President to understand why my kids are “special needs” — they are literally losing their minds as a result of this genetic cholesterol illness.  In fact, 22 million children in the US are estimated to suffer from chronic and life threatening rare diseases like Addi and Cassi which are causing a major crisis in our education and health care systems.

I spend my days trying to educate people about cholesterol. Cholesterol problems are mainly genetic in origin. Many roads are leading to the Niemann Pick Type C gene on Chromosome 18 as one of the major drivers of cholesterol in the human body.  The NPC gene regulates human cholesterol at the cellular level and we are all born with this gene.  This is why Nobel  Prize cholesterol scientists Drs. Brown and Goldstein are studying the gene and publishing papers about Niemann Pick.  Addi and Cassi were simply born with genetic defects on this cholesterol processing gene have a fatal and relentlessly progressive neurological condition as a result.

The Niemann Pick Type C gene is also thought to be a culprit in obesity. Last year, I posted a blog about the genetic link to obesity and the Niemann Pick Type C gene from a research group at Inserm in France.  Given the First Lady’s interest in helping solving obesity in America, she might want to read it.

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