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.

Tylor made the Notre Dame Newsletter

 White-Richardson, White & Simon Family Visit

CRND was pleased and honored to host the White-Richardson, White and Simon family on March 23^rd. The visit was the culmination of a continuing conversation between the family and students Natalie Bott and Aaron Patwahl (see RAREhealth Exchange on page 6).

Ms. Jennifer White shared her experience navigating the medical system when trying to understand her son’s (Tylor White-Richardson) disease. She delved into the medical literature, joined family support groups and sought out medical experts. When the leading hospital in Iowa could not provide a diagnosis, she specifically requested a referral to the Mayo Clinic. Mr. Brian “Sy” Simon has been at Jennifer’s side and wholly supports their family.

A Mayo physician did finally provide the diagnosis of Niemann Pick Disease Type C. Dr. Marc Patterson, in particular, began an incredibly supportive relationship and continues to attend to Ty with compassion and humor. Both Jennifer and Sy appreciate Dr. Patterson’s style and told pre-professional students, “Be a person, not a clinician, and treat patients as people.”

The family handles challenges with aplomb. When Tylor required the use of a wheelchair, they found the right resources and had one custom-built. They had a wheelchair-accessible van re-fitted for Tylor and travel across the country. Jennifer, Ty and Sy maintain an active lifestyle and help mentor new families.  Because the National Niemann Pick Disease Foundation has been a valuable resource, they keep strong ties.

Dr. Patterson Trip to Notre Dame

March 2, 2012 - Marc Patterson, M.D. Chair - Division of Child and Adolescent Neurology, Professor of Neurology, Pediatrics and Medical Genetics, Director - Child Neurology Training Program Mayo Clinic. Dr. Patterson is board certified in psychiatry and neurology (with special qualification in child neurology and in neurodevelopmental disabilities). Dr. Patterson is on the Scientific Advisory Board for the National Niemann-Pick Disease Foundation.  When my frail bark starts from the shore, Far out across the unknown tide; May some good angel guide me o'er, In safety to the other side! David Fletcher Hunton Grand Haven Daily Tribune,February 15,1902 At some point or another, most of us realize the frailness of the bark upon which we sail. For many, steeped in a cultural denial of death and blessed with good health, this realization comes late. But, in the realm of rare diseases, the awakening to pure vulnerability often comes at an early age and well before the 72 years Hunton had secured when he wrote this verse. When this awakening comes, it often appears as an “unknown tide” – in waves of unanswered questions and grief. Then, it is vital, not to sink into hopelessness or denial, but as another poet sets it, “to take arms against a sea of troubles.”1 In our species, we first take up arms against the dark and unanswered troubles by naming them and pushing away speechless sorrow. The great botanist and father of classification, Carolus Linnaeus, was called “God's registrar” and he wrote about the significance of classification, which always begins at the boundary of the unknown deep: “The first step in wisdom is to know the things themselves; this notion consists in having a true idea of the objects; objects are distinguished and known by classifying them methodically and giving them appropriate names. Therefore, classification and name-giving will be the foundation of our science .” (Systema Naturae ,1735. Trans., M. S. J. Engel-Ledeboer and H. Engel (1964), 19.) On March 2, Dr. Marc Patterson visited the students and faculty of the CRND and delivered a seminar, which would have pleased old Linaeus, “An introduction to neurometabolic disease.” Last year, Patterson taught an in-depth class on NP-C disease; this year, he placed NP-C in the broad framework of metabolic diseases of the nervous system, focusing on the common characteristics which substantiate the working classification:“inborn errors of metabolism (IEMs).” This delicate phrase names the general class of more than 5,000 distinguishable disorders, which are now visible and subject to relational analysis and systematic experimentation.  Dr. Patterson explained IEMs as "genetic disorders in which absence or malfunction of the gene product perturbs the internal milieu." He described a variety of gene products, all of which are subject to errors that potentially manifest in the appearance of disease: enzymes, structural proteins, transporters, channel constituents, receptors, and transcriptional and translational factors. Given the number of factors that can be deranged in the process of gene transcription and translation, Patterson explained how the percentages of people affected by some form of rare disease quickly mount up. In the United States about 1 in 10 people has been estimated to suffer with a rare disease. Still, there is a significant problem with the undercounting of rare diseases.  According to Patterson, underestimation of disease prevalence may occur because of overreliance on classic disease profiles. These can blind us to the atypical presentations resulting from mild, complex, and combined genetic errors. Additionally, where the observable expression of a disease is developmentally staged or results from multiple downstream effects over time, we miss in our estimation of disease prevalence. Patterson illustrated the problem with an Italian study of Fabry Disease. The study found an actual incidence of 1:3,100 versus a previous estimate of 1:50,000 in a region of Italy because it captured atypical, mild and late-onset cases, which were previously overlooked. Compared to the classic profile of Fabry, atypical cases in this region ran 11:1. Underscoring the complexity of genetic unfolding and the general inadequacy of the models, Patterson summarized, "Whatever we're thinking, however complicated you think a system is, it is really much more complicated."  Dr. Patterson's review of IEMs outlined known genetic mechanisms, molecular mechanisms, and the correlations between genotypes and phenotypes. He illustrated particular disorders and described symptomatic manifestation for the audience. The genetic mechanisms underlying IEMs include loss-of-function mutations, gain-of-function mutations, regulatory mutations, multiple downstream effects, and mutations based in epigenetic influences and Mosiacism. Examples of small molecule diseases take in amino acidopathies, organic acidopathies, urea cycle defects, fatty acid oxidation defects, disorders of oxidative phosphorylation, porphyrias, and neurotransmitter disorders. These conditions are associated with phenotypic presentations, including severe life threatening neonatal catastrophes, milder episodic dysfunction and cerebral organic acidemias. Examples of large molecule diseases comprise sphingolipidoses, mucopolysaccharidoses, neuronal ceroid lipofuscinosis, and glycoproteinases. These conditions share phenotypic traits such as progressive neurodegeneration, organomegaly, dysostosis, coarsening of the features, ocular changes, and cutaneous lesions. Many of the small and large molecule diseases share a common problem of deficiencies in enzymes, cofactors (these activate enzymes) or enzyme transporters. Complex IEMs include congenital disorders of glycosylation (CDG), childhood ataxia with central hypomyelination (CACH - vanishing white matter disease) and Cockayne's syndrome. These complex disorders are characterized by combined symptoms of large and small molecule diseases (i.e., features of slow deterioration with episodic decompensation).  According to Patterson, critical factors for diagnosing and treating IEMs currently embrace history, examination, presentation, and investigation. Elements to be considered in the patient's history include membership in an at-risk population, consanguinity, multiple miscarriages, and certain problems during gestation. Neonatal issues may also give an early indication to genetic disorders (eg., jaundice, organomegaly, acute encephalopathy). Beyond infancy, other signs may aid diagnosis: dietary preferences and aversions, unusual odors, episodic decompensation, mimicking static encephalopathy and problems with developmental progress (eg., too slow or significant regressions). Patterson predicted that in the future, genetic testing will play an increasing role, although he noted social concerns and the importance of understanding that an identified genetic issue might not actually manifest phenotypically until late in life. During this highly technical presentation, Dr. Patterson made a special point of conveying to students his testimony on the art of medicine. Given the daunting scope of IEMs and the very real suffering signified by each of them, it was helpful to hear Dr. Patterson's philosophy on treatment. He is after all, a practitioner. He faces the daily challenge of nurturing the inner resilience of his patients and their families as the waves of unanswered questions beat against them. I want to emphasize one thing to you. There are no untreatable disorders. We can treat everybody. We can help everybody – however rare their disease. Whether or not there is 'a curative' ...there is almost no curative therapy for anything - or [often no] disease modifying therapy. Just by giving people good general medical care, you make a huge difference. You've got to educate them about the disease. You've got to educate their networks about the disease. And, learn from them – it's a two-way process. You've got to support their nutrition, make sure they're fit, make sure they've got all the support that society can get. And, that can be a nightmare – navigating your way through the different systems that exist. Does it make a difference? Yes! Cystic Fibrosis. You've all heard of it. One of the most common recessive, lethal diseases in the Caucasian population. When I was a medical student starting in the '70s, hardly anybody survived their teen-age years. Now, the median survival is up into the 40s and its getting up towards 50! Is there a curative therapy? Well, there was just a paper published about a disease modifying therapy. But [until now] there's been nothing! So, what changed? People developed specialized clinics. They started to get aggressive about treating these children. They developed protocols. They updated them. They tracked progress. And, they made a huge difference in the survival from this disease. So, that's a great model for all rare disease. You can make a huge difference. You shouldn't be a nihilist. You can help all of these people make a big, big difference. That is probably the most important message of this talk. Thus, the brilliant lodestar of the healer appears above the dark sea - attend its light and chart a course across the sea of uncertainty that is rare disease medicine. tagline: Patterson, Marc C. Classification: Angel of Mayo. 1 William Shakespeare, Hamlet, 3.1 .

World Rare Disease Day-Meet Alejandra

Patient Stories of Hope and Inspiration

'Meet Alejandra!'

My name is Alejandra Islas. I'm a kindergarten teacher, living in Mexico City, Mexico. I was diagnosed with Hypereosinophilic Syndrome (HES), in 1998, at a time when medical databases showed only six cases with symptoms similar to mine, and with a life expectancy of 6 months.

My symptoms started 13 years ago, while on vacation in Argentina. Initially I had itching on my torso, but quickly started to feel tired, breathless and have heart and lung pain. In what seemed unrelated, I started to feel utter discomfort in my feet. It was as if they were burning, got swollen and I could barely walk on my own.

An initial TAC and x-ray of my lungs showed some strange moving lesions which appeared to be related to parasites. Also my feet continued to bother me and I wasn’t feeling my legs from the knee to the bottom anymore and some skin lesions started to appear… they looked like chickenpox or scarlatina on my torso, vasculitis on the face and a trail of insect bites around my calf. I went to see a dermatologist, who was baffled by them but didn’t think they were a serious condition because the symptoms didn’t match to those of an infection, and he didn’t think the heart pain was related.

Luckily, my father and brother had worked in the pharmaceutical industry, they knew blood tests could reveal something still undetected. A blood test showed that my EOS count was 79,000 (when the upper limit was 6,000). Tests to check for lupus, vasculitis, scleroderma, parasites and more were ordered, but all showed up negative. Some tests were even sent to the US to the CDC in Atlanta, GA, however at that time no one could determine an explanation for my symptoms.

Over the next few months I was feeling worse and worse. Chest pain, tiredness, general sickness, awful pain in my abdomen, joint pain and hot bruises all over my body, and I couldn’t even walk anymore. I had lost several pounds and now I could barely eat.... my body started to reject all food.

In the hospital, doctors prescribed four steroids to at least calm down the pain and to see if that would help with the hypereosinophilia, and it did! And I was finally diagnosed with HES. I am currently treated with a low dose of inhaled beclomethasone, although recently it has become really hard to find around the world.

I have a strong faith and I am certain God performed a miracle where my physicians, all of them at Medica Sur Hospital, in Mexico City, have been His instruments. And of course, I also thank God for my family, without it wouldn't be possible for me to be here today.

Although I live in Mexico, I wear jeans and made denim ribbons to share with family, friends and all those who ask about the meaning of them. I also wear my special bracelet made for this purpose. I am glad to be able to contribute my experience and advice to support others with HES!!

Thank you and God bless you all!!

Alejandra Islas
Mexico City, DF

World Rare Disease Day-Meet Michelle

Patient Stories of Hope and Inspiration

'Meet Michelle!'

I am 49 year old, single mother who was an US Air Force Reservist, and also worked as a Nurse for 15yrs. In 1999, some strange symptoms started to occur, like bumping into walls, tremors, falls, numbness, tingling, in feet, legs and hands. I also experienced bowel and bladder problems, all within a month that I was off work. I went to a top specialist at UCLA, U of M Ann Arbor, and a few others. I Was told I was a difficult case after many test and exams. I had two separate groups of symptoms. One was cerebellar, which was confirmed by MRI that showed atropy of cerebellum, but there was no answer for my Upper Motor Neuron signs. And most testing was negative or normal.

After 11yrs of having a partial diagnosis of SCA (Spinocerebellar Ataxia), unidentified type. They finally found a rare abnormal gene mutation SET X (or Senataxin). This gene had only been discovered in 2004 and they are still learning about it. They found the UMN disease and my very rare diagnosis is ALS4 with a cerebellar ataxia overlap. I am joining as many clinical trials I can to help find treatment and a cure. I am an advocate locally as part of the Detroit Area Ataxia Support Group. And I dedicate as much time as possible to spreading awareness. I am a member of the National Ataxia Foundation and now the ALS foundation. I am still walking with a walker short distances and waiting for my customized wheelchair to be delivered. I take online classes at University of Phoenix for Computer Information Systems and Graphic Web Design.

Michelle DeCiantis
Michigan

World Rare Disease Day-Meet Anna

Patient Stories of Hope and Inspiration

'Meet Anna!'

Fourteen and a half years ago, our lives were changed forever. Our one week old baby girl was diagnosed with a disease that we thought was created in a novelist's imagination. We quickly learned that it was a very real, yet rare, disease that would nearly claim our daughter's life.

Our daughter Anna was born with Maple Syrup Urine Disease, a strange name for a potentially fatal disease. Since she was a week old, Anna's life has been dictated by a very restricted diet, frequent blood tests, and constantly fearing elevated amino acid levels that lead to metabolic crisis. Yet she has not let these challenges hold her back from her ambitions.

Anna competes in track and soccer through Special Olympics. She also participates in the yearbook committee at her middle school, and volunteers at an equine therapy ranch. She strives every day that although she may live with a rare disease, this disease will not keep her from enjoying life to the fullest every day.

Paula Ruter
Michigan

World Rare Disease Day-Meet the Wilson Brothers

Patient Stories of Hope and Inspiration

'Meet the Wilson Brothers!'

My brother, Marshall is my Hero! He saved my life. At 17 months of age, he was diagnosed with a RARE Leukodystrophy called Krabbe's Disease. A genetic disorder affecting the nervous system and it's communication to the brain. There is NO CURE and it is fatal!

Once my family and our doctors determined what was affecting my brother, we were encouraged to have me tested. Exactly one month after his confirmed diagnoses, I tested positive for the same disease. The only difference between the two of us is that I have no symptoms and became a candidate for a cord blood transplant. At four months of age I had a CBT and though I had complications with the chemo treatments, the transplant has been considered a success, as a recent MRI showed no disease activity. Thank You Brother for Saving My Life!

Marshall is now 2.5 years of age and I am 15 months old. Though I am delayed a bit, with all the therapies, love of my family, and spiritual pep talks from my brother, I am thriving, and achieving my developmental milestones, just as my brother hoped for. Without his heroism, I would not be able to SEE my brother, play with my toys, watch a flower bloom, and kiss his angelic cheeks (my brother is blind). I would not be able to giggle and babble and one day tell my brother that I love him, ‘Thank You’, and that he is my hero (my brother never spoke his first word). I can hear my Mommy's voice sing to me, my Daddy talk about fishing, and the fun activities of my brothers and sister (my brother is deaf). I can roll everywhere and sit up; I even get to hug on my brother. I get to smile, eats solid foods, get older. I will go to school, possibly college, and someday I hope to marry and have a family of my own and tell my children the story of my gene family. MY BROTHER................MY HERO!

Tammy Wilson
Oregon

World Rare Disease Day

Everyday during the month of February and leading up to World RARE Disease Day on February 29th, the Global Genes Project in partnership with the RARE Project will be featering stories of Hope and Inspiration. They are asking that we share these stories and I would love if you would pass them along too....


Patient Stories of Hope and Inspiration

'Meet Peyton!'

Peyton isn't that much different than any other four year old if you ask her. She loves to color and dance and she is a ‘Yo Gabba Gabba’ fanatic. Luckily, she is still blissfully unaware of the stares directed her way when we go to the grocery store or the playground. Peyton was born with Nager Syndrome, a very rare condition that results in craniofacial and upper extremity anomalies. As a result of her lower jaw not developing fully, she underwent a tracheostomy at 3 days old to breathe and a gastrostomy at 3 weeks old to eat. She has severe bilateral hearing loss and has been wearing hearing aids since she was a few months old. She has had two jaw distractions and three hand surgeries. Her life has been filled with xrays, CT scans, doctor appointments, hospitalizations and therapy sessions.

Despite the rarity of Nager Syndrome, with the internet we were able to learn much more in the first few days of her life than what the hospital could provide from their outdated genetics books. We have been able to reach out to other families whose children have Nager Syndrome and have even met a few in person. We are blessed to have strong support from our family, but through the Nager and Miller Foundation we have also felt part of another "family" who understands the unique challenges and joys that we experience with a child like Peyton. Through our blog www.peytonsparents.blogspot.com we have had many families reach out to us who have children that are newly diagnosed. We even had a family contact us before their child was born, and seeing Peyton's smiling face brought them hope in a time of great stress.

The Global Genes/RARE Project, is just one more "family" that we can feel a part of. In December, I received a bracelet as part of the 7000 Bracelets for Hope project. Although I have never met the jewelry designer, Eileen has made me feel such hope that there are others just like her in the world who will make Peyton's path easier.

Thank you!

Tracy Smith
Utah

NIH Cyclodextrin Trial

National Institues of Health Announces Cyclodextrin Clincial Trial For Fatal Cholesterol Disease Called Niemann Pick Type C


August 16, 2011 by Chris Hempel
Over the past three years, many Niemann Pick Type C families as well as physicians treating NPC patients worldwide have contacted Dr. Caroline Hastings and I regarding Addi and Cassi’s treatments with hydroxypropyl-beta-cyclodextrin.

Since sharing our intravenous (IV) and intrathecal (IT) cyclodextrin treatment protocols with NPC families and doctors in the U.S. and other countries, many NPC patients have started cyclodextrin therapy.

Currently, I know of 11 NPC patients in various countries receiving cyclodextrin treatments – six are receiving intrathecal (IT) treatments to allow cyclodextrin to reach the brain.

With many Niemann Pick Type C families scattered around the world, it’s difficult for people to obtain information on cyclodextrin and determine how they might be able to get started with treatments. In the past month alone, I have been contacted by families located in Italy, Spain, Germany, Dubai and Japan and all are interested in cyclodextrin treatments.

I am writing this blog in the hopes it can help NPC families in other countries who are seeking information on cyclodextrin and help them understand how they may be able to treat their loved ones with this potentially life saving sugar compound.

NIH Announces Intracerebroventricular Clinical Trial with Cyclodextrin
In the United States, the National Institutes of Health (NIH) has announced an intracerebroventricular (ICV) clinical trial with cyclodextrin. Dr. Forbes “Denny” Porter is running the clinical trial with an NIH Bench-to-Bedside Grant and with the help of the NIHs Therapeutics for Rare and Neglected Diseases (TRND) program and the National Center for Advancing Translational Sciences (NCATS).

Details are limited on what the inclusion/exclusion criteria will be for the NIH cyclodextrin clinical trial and they are still preparing their IND for the FDA and conducting pre-clinical studies.

The exciting news for NPC families is that the NIH has announced that they will pursue delivering cyclodextrin directly into the brains of patients using an Ommaya reservoir. An Ommaya reservoir is an intraventricular catheter system – a catheter is implanted into the brain and it is attached to a reservoir implanted under the scalp.

Dosing is still being determined by work done on NPC animal models, including the naturally occurring NPC cat model. I am sure dosing will be quite similar to what we are already giving to Addi and Cassi (possibly every two week cycle) as the FDA likes to base clinical trials from animal data. The NPC cats receive bi-monthly doses of cyclodextrin and Dr. Hastings based our initial bi-monthly IT treatment plan from the same cat studies.

Getting Cyclodextrin Into The Brain and Past Blood Brain Barrier
In my previous posts, I have detailed our plans with trying to get cyclodextrin into the twins’ brains. In October 2010, Dr. Hastings received FDA approval to start the twins on intrathecal injections of cyclodextrin into their spines. Since Addi and Cassi were the first in the world to ever receive this treatment, safety was a primary concern.

We initially started with intrathecal injections into the spine because we had to prove that the twins would not have an adverse reaction or die from an injection of cyclodextrin into their central nervous systems. Also, intrathecal treatment was less invasive. Per our FDA approved protocol, the twins must be hospitalized and monitored after intrathecal treatments. At first, they were monitored for 24 hours. Currently, we’re down to three hour observations following IT treatments.

Since October 2010, Addi and Cassi have received over 20 intrathecal injections of cyclodextrin into their spines as we work towards a permanent solution. The twins were going deaf before we initiated intrathecal cyclodextrin therapy. We have now restored their hearing to normal levels which is quite encouraging.

We also continue with our weekly IV infusions of cyclodextrin into their bloodstreams and are also looking for ways to deliver cyclodextrin into the lung as IV and IT treatments do not appear to reach the lung.

Medtronic SynchroMed Pump To Deliver Cyclodextrin
Over the past year, we have been creating an intrathecal protocol with the help of Medtronic and Johnson & Johnson and plan to implement a Medtronic SynchroMed pump system to deliver cyclodextrin into the brains of the twins. Medtronic is currently conducting final pump studies with cyclodextrin and we hope to re- submit data to the FDA and our hospital Institutional Review Board (IRB) in September.

We are working towards a SynchroMed pump solution because the NPC mice data shows that low continuous dosing is effective in completely stopping NPC. NPC mice are now being treated like diabetics. Cyclodextrin may need to be given on a frequent basis (perhaps daily or even weekly). We simply don’t know. We will start with a weekly bolus of cyclodextrin through the pump.

The Ommaya port does have many advantages, however, it does not offer frequency of dosing — it’s an access port versus an automatic system. In addition, it is my understanding that the Ommaya requires a patient to be in a hospital setting to receive a treatment (in the United States). SynchroMed pump refills can be made in an outpatient setting once the pump is installed and the pump lasts about seven years.

Choosing Between Ommaya and SynchroMed
The beauty of the Ommaya system is that you know for certain that cyclodextrin is reaching the brain. I believe the NIHs plan to pursue the Ommaya option is the right decision for the clinical trial and to determine efficacy. I hope many NPC patients will be eligible to participate in the clinical because I believe cyclodextrin could be life saving.

Since Addi and Cassi have been receiving cyclodextrin treatments for almost three years, they will not be eligible for the NIH trial. Many other NPC patients, especially those in foreign countries, will also not be able to participate in a U.S. clinical trial and therefore may want to pursue treatments in their individual countries.

Hugh and I continue to look at a longer term and permanent solution for cyclodextrin treatments as it appears cyclodextrin will be a life-long treatment. We are looking for a solution that provides flexibility on dosing and also keeps our kids out of a hospital setting as much as possible.

Medtronic’s data shows high catheter placement into the spine will allow cyclodextrin to reach brain and we will be taking this chance. We know that our intrathecal treatments in the lower spinal area are reaching the twins’ brains as we have restored the twins’ hearing to normal levels. But there are still lots of unknowns and many risks too. There is no easy decision and no right answer.

Also, I am not sure if an infant can get a SynchroMed pump placed so the only option may be an Ommaya. The NPC animal data shows that the sooner the animals start cyclodextrin treatment (BEFORE symptoms are evident) the healthier the animals stay.

Exciting Treatment Options
The good news for NPC patients and families worldwide is there are now promising treatment options to pursue which were not available before. Doctors can look at both Ommaya or SynchroMed solutions to get cyclodextrin into the brain and consider these options today for their patients.

I believe we’re ultimately going to need combination therapy to treat NPC as the disease impacts every cell in the body. We’ll need ICV or IT to reach the brain, IV to reach the organs and tissues and probably some type of inhalable HPBCD to reach the lung.

These are the options we are pursuing to try and save Addi and Cassi’s lives. We hope this information will help other families as they look for any possible way to save their loved ones from this wretched disease.

For more on Addi and Cassi go to their website.

Walk 4 Wishes

Grab your tennis shoes, comfy pants, the stroller for the kids, the dog and join us on October 2nd at Murphy Park for the 2nd Annual WALK 4 WISHES from 8:30am to 10:30am.

All donations will help grant wishes to kids with life threatening illnesses in Iowa. Make a Wish of Iowa grants an average of 200 wishes a year. So we need your help to keep granting more wishes for children like Tylor.

Tylor was granted his wish in 2008! Make A Wish flew him to New York to meet Brett Favre. This is a memory no one can ever take from our family. So we as a family are challenging you to come walk with us and if you can't walk with us please donate. Every little bit helps...you can either contact Make A Wish or myself to make a donation.

Thank you for your support!!

More news on Cyclodextrin

Results in Mice May Help Shape Clinical Trial for Children With Rare Fatal Disease

By Amy Dockser Marcus

It’s a well-known maxim in science that curing a disease in a rodent doesn’t guarantee the same results in a human being. But new research on using the drug cyclodextrin in mice is likely to help shape a clinical trial being planned for children with a rare and fatal genetic disease.

Scientists led by John M. Dietschy at the University of Texas Southwestern Medical School just published a paper in the Journal of Neuroscience on continuous cyclodextrin treatment for Niemann-Pick Type C, a fatal neurodegenerative condition in which cholesterol builds up in tissues and organs. The treatment not only kept mice alive but prevented the cognitive decline that is one of the hallmarks of the illness.

When delivered directly into each rodent’s central nervous system via the spinal column in order to better reach the brain, cyclodextrin “completely prevented the expected neurodegeneration,’’ the authors wrote.

The paper’s publication is especially propitious because the NIH announced earlier this year that it plans to start a clinical trial treating NPC patients with cyclodextrin, hopefully some time in 2012. One of the key issues still being discussed is whether to deliver the drug directly into the central nervous system (as was done with the mice in the paper) or through an infusion into a vein that carries the drug into the general circulatory system.

The new paper will fuel and shape that ongoing debate. It found that delivering cyclodextrin directly to the brain requires lower doses and appears to be more effective in reversing the cholesterol defect than infusions into a vein.

“It will be a very influential paper in the field,” scientist Daniel Ory tells the Health Blog. Ory ought to know: he is the principal investigator on an NIH grant focused on getting cyclodextrin from the lab into NPC patients. He’s also working closely with NIH’s Therapeutics for Rare and Neglected Diseases program, which selected NPC and cyclodextrin as one of its pilot projects to attempt to repurpose drugs for use in rare diseases.

Dietschy, who has published a number of previous papers on cyclodextrin and NPC, acknowledged that continuous, life-long administration of the drug into the central nervous system using a pump isn’t easy — even in a mouse. In children, surgery is required to install, remove, and replace pumps, and the devices can become infected. Still, Dietschy says, if more data and studies back up the findings, he believes the technical obstacles can be overcome by surgeons.

Rumors about the paper’s findings were already creating a buzz among some in the NPC patient advocacy community even before it was published. In May, the National Niemann-Pick Disease Foundation, an advocacy group, sponsored a teleconference with Ory and NIH clinician Denny Porter to discuss the planned cyclodextrin trial.

In response to a question by a parent asking about the possibility of doing a trial using the delivery method described in the Dietschy paper, Porter said that there would be additional regulatory hurdles involved since it is a “huge jump in risk or risk-benefit ratio” to think about delivering the drug directly to the brain rather than through a vein.

Ory tells the Health Blog that investigators want the most efficient delivery method, but also one that can be rapidly moved into the clinic. He says the risks of injections into the spinal column, could potentially slow down the opening of a trial. Still, he agreed that the paper’s findings will inform the discussion.

One human experiment is already underway in twin girls with NPC, who have been receiving cyclodextrin infusions under the FDA’s compassionate use program.

Chris Hempel, the mother of the girls, Addison and Cassidy, tells the Health Blog they will submit a protocol for hospital approval to install a pump in each girl’s spine that will start delivering continuous cyclodextrin infusions to the brain.

Hempel says she closely follows Dietschy’s research, reading each paper. “As more research comes out, we can modify’’ the approach,” she says.

Dietschy says it’s too early to tell how or if the new results will be applied to patients. In the meantime, he says he plans to observe a colony of mice receiving continuous infusions to see how they progress. Researchers are still working on the technical issues but Dietschy says he can’t help but wonder: Will mice treated this way go on to live a normal life? And if so, could children?

Photo: Associated Press
**Taken from the Wall Street Journal Health Blog**

Rare-disease studies seek online giving

Website invites micro-donations for unusual illnesses.
Amber Dance

Those wanting to raise awareness about a rare disease will be able to take advantage of an initiative being launched later this year: a website that connects research projects with members of the public who can donate just a few dollars to help to develop cures.

The plan, called the Global Genes Fund, will "democratize the research proposal game", says Irwin Feller, an emeritus professor of the economics of science and technology at Pennsylvania State University in University Park.

The idea has been developed by the Children's Rare Disease Network, a non-profit organization based in Dana Point, California. The network plans to set up a test site by the end of 2011, with a formal launch in 2012. Potential funders will be able to choose from projects with funding goals of US$10,000-150,000. The fund will post proposals that are deemed by its committee to be likely to succeed within three to five years — that is, within the often-short lifetimes of people currently affected by the diseases.

Rare, or 'orphan', diseases are defined as those that afflict five or fewer people out of every 10,000 in the European Union or fewer than 200,000 Americans. The diseases are devastating but overlooked. Pharmaceutical companies are naturally interested in blockbuster drugs that will be taken by many people, whereas governments are often perceived as focusing their limited resources on more common conditions.

There is some funding: for example, in 2009 the National Institutes of Health announced US$24 million for the Therapies for Rare and Neglected Diseases programme to developing medicines for orphan diseases. But there is simply not enough money to support research on all rare diseases. There are some 7,000 orphan diseases affecting an estimated 350 million people worldwide. Of those, 75% are children, says Nicole Boice, founder and chief executive of the Children's Rare Disease Network. Parents often shoulder the burden of advocacy, running cake sales and other fund-raising events to support research.

Many hands
With the Global Genes Fund, Boice hopes to raise money and awareness to a level that is impossible for individual parents and scientists. She was inspired by the success of microloan website Kiva.org. On Kiva, users browse a list of individuals worldwide who need a small loan to pay for business expenses, home improvements or other projects. Through loans of as little as $25, Kiva has raised $22 million since it was founded in 2005.

The Global Genes Fund will solicit money for defined short-term projects, Boice says. For example, it might support whole-genome sequencing for a child with an undiagnosed disorder. Or it might pay for children with a rare condition to travel to a trial centre.

The fund will also seek corporate sponsorship. Those larger gifts will help to cover projects that don't receive sufficient micro-donations, Boice says.

"It's not just the funds, it's the awareness" that the fund will raise, says Audrey Gordon, president and executive director of the Progeria Research Foundation, based in Peabody, Massachusetts. The foundation is a non-profit organization that promotes the study of progeria, which causes rapid ageing. The global nature of the new fund means that more families affected by rare diseases will find others dealing with the same problems, advocates say.

"There's a serious lack of funding for these various rare diseases," says Chris Hempel, a Reno, Nevada-based advocate and mother of twin girls who have Niemann–Pick type C disease also referred to as 'childhood Alzheimer's'. "We're all in the same boat and no one's getting drugs."

Regarding the fund, "I think it's an extremely interesting project", says Steve Groft, director of the NIH's office of rare disease research. "It will meet the needs of some of the rare-disease-community members." Even a tiny $50,000 pilot trial could give researchers enough data to apply for more funding, he adds.

**Taken from Nature News**

Ducks afloat for NPC

TURLEY — Ducks for Bucks is a non-profit organization created in memory of Breann Chavez who passed away at the age of 3 from Niemann-Pick Disease. Families faced with NPD are faced with a small window of time with their sick child.

Ducks for Bucks was created to help alleviate some of the financial burden these families face so they can focus on enjoying the few years they have with their child. Ducks for Bucks 2011 will take place at Wines of the San Juan, from noon to 5 p.m. on Saturday.

This is a family fun day filled with live music, games, raffles, silent auction, food, wine tasting and entertainment for kids of all ages, along with the annual Dainty Duck Dash, a rubber duck race with chances to win cash prizes.

Niemann-Pick Disease is a term for a group of diseases which affect the metabolism and which are caused by specific genetic mutations. NPC is a genetic disease in which the body does not break down cholesterol and instead stores it inside major organs - like liver, spleen and brain. This storage leads to many complications both physically and neurologically and begins to deteriorate the bodies of the young victims it attacks.

The three most commonly recognized forms of the disease are Types A, B, and C. The National Institutes of Health has referred to NP-C as “childhood Alzheimer’s” because of the neurological similarities between the two diseases.

At this point, there is no cure for NPD. All cases are fatal, which makes time incredibly valuable to these families.

For most families facing Type C, neurological symptoms begin appearing between the ages of 4 and 10, with children appearing completely normal until this point. Generally, the later neurological symptoms begin, the slower the progression of the disease.

Once the neurological breakdown begins the body follows. These children lose all mobility; they lose their ability to speak, play, and even eat, leaving many of them to get their nourishment from a feeding tube.

Many suffer with seizures, and other pains they cannot express, leaving caregivers constantly guessing. The vast majority of children die before the age 20 and many die before the age of 10.

NPD is a genetic disease in which both parents must be carriers for their child to become affected with the disease. Each child has a one in four chance of having NPD.

Due to the late onset of the disease, many parents do not realize they are taking this risk until it is too late, resulting in many families with multiple children dying from NPD.

Ducks for Bucks is recognized by the IRS as a public charities non-profit and does have a 501(c)(3). All money raised goes directly to helping families with whatever their greatest need is at the time.

For some that means medical bills, co-pays, and equipment. For others it is just unexpected daily living expenses due to their child’s illness. Those not abe to attend the race in person may purchase a rubber duck for $5 online.

Although you will not physically receive your duck, it will be entered in the Dainty Duck Dash for a chance to win $1000 cash for the first place duck.

$500 will be awarded for second place and $250 for third. Winners do not need to be present to win.

Visit the website to start your duck in training today for the big race.

For more information, call (505) 632-7649 or go to http://www.ducksforbucks.org/

**Taken from the Farmington, New Mexico Daily Times**

Rare Diseases: Will push for new drugs pay off?

Cassidy Hempel, 6, waves at hospital staff with the help of her mother, Chris, at the Children's Hospital and Research Center in Oakland, Calif., Friday, March 18, 2011. Cassidy and twin sister, Addison, are being treated for a fatal disorder called Niemann Pick Type C disease. (Credit: AP Photo)

(CBS/AP)Call it the rare disease gap. Scientists have identified more than 7,000 diseases that affect fewer than 200,000 people, but treatments are available for just 200 of the diseases.


But now there's a move to close the gap. The National Institutes of Health this fall will open a center to speed genetic discoveries into usable therapies, doing some of the riskiest early-stage research in hopes companies then will step in.

A new International Rare Diseases Research Consortium is pushing for at least 200 more treatments by 2020, in part by pooling the work of far-flung scientists and families.

Rather than starting from scratch, the FDA is pointing the way for manufacturers to "repurpose" old drugs for new use against rare diseases, publishing a list of those deemed particularly promising.

And legislation recently introduced in the Senate, called the Creating Hope Act, would offer drug makers another financial incentive - a voucher promising fast FDA evaluation of their next blockbuster drug in return for developing a therapy for a rare or neglected disease that disproportionately affects children.

"We have to give drug companies a reason to go into this market," says Nancy Goodman of Kids v Cancer, a group pushing the legislation. Her son Jacob died at age 10 from a type of brain cancer that has no good treatment.

Pharmaceutical giants are starting to show some new interest in rare diseases, traditionally a niche market for small biotech companies. The practical reason: Blockbusters are drying up, says Dr. Ed Mascioli of Pfizer Inc., the world's largest drug company.

Some other companies, including Novartis AG and GlaxoSmithKline PLC, also have begun rare-disease programs.

But NIH Director Dr. Francis Collins says all the activity reflects a larger promise. "Getting a home run with a rare disease sometimes points you in a direction that will be beneficial for common diseases," he told The Associated Press.

That's the argument put forth by Chris Hempel, of Reno, Nev. Her 7-year-twin girls have been getting injections of an experimental drug for Niemann-Pick Type C (HPC), a disease that causes cholesterol and other fats to build up inside cells, harming the brain and other organs until patients lose the ability to talk, walk and swallow. Only 500 children worldwide are known to have it. But a drug that could flush out that build-up, Hempel contends, just might point to a new route to fighting heart disease or Alzheimer's.

Hempel isn't alone in her quest to repurpose common drugs. Consider progeria, a disease that rapidly ages children until they die of a heart attack or stroke, usually before their teens.

Collins' lab at NIH uncovered the gene defect behind progeria, research that he says he pursued only because of meeting another mom, Dr. Leslie Gordon, founder of the Progeria Research Foundation, and her son, Sam, who has the disease. Today, clinical trials are under way using a failed cancer drug named lonafarnib that promises to block some of the progeria mutation's effect.

There are an estimated 150 progeria patients worldwide, but Gordon points to growing evidence that the culprit protein may play a role in the heart disease that comes with regular aging, too.

** Taken from CBS News Health Watch **

Rare Diseases in the Spotlight

By Marissa Cevallos, HealthKey

1:55 p.m. EDT, April 27, 2011

Rare diseases are likely to get more attention now that an international consortium of patient advocacy groups and research funders has vowed to deliver 200 new therapies by 2020. For people with these diseases, such attention must seem long overdue.

Drug companies currently don’t have much incentive to develop drugs for diseases that affect fewer than 200,000 people, but almost 7,000 rare diseases exist affecting a total of about 25 million Americans.

Many are caused by mutations in a gene. The National Institutes of Health is opening a center in the fall to translate research findings in genetics to usable therapies, the Associated Press reports.

The NIH already has grant programs to spur research in rare diseases. The NIH's Therapeutics for Rare and Neglected Diseases program has a pipeline of projects. Its pilot projects offer a glimpse into some of the diseases that, though rare, can nonetheless have debilitating consequences.

—Schistosomiasis (also known as bilharzia or snail fever): Infection begins when a parasitic worm carried by freshwater snails penetrates the skin and lays eggs in blood vessels. First come rashes, then fever and chills, followed by liver and other organ damage over time. Researchers recently decoded the genomes of two schistosomiasis-causing parasites, which may allow researchers to find ways to inhibit the parasites’ growth. About 200 million people worldwide have the disease, and 280,000 die from it each year.

—Niemann-Pick Type C: In this condition, fatty deposits accumulate in the spleen, liver, lungs, bone marrow and brain. Type A, the most common, is fatal in infants. Type C can appear early in life or in young adulthood; it causes brain damage and ultimately can affect walking, swallowing, seeing and hearing. Only about 500 children in the world are known to have Type C. Researchers have found two genes that can contribute to Type C and Type D, but progress is slow.

—Hereditary inclusion body myopathy: Usually starting in young adulthood, the disease causes muscle-wasting, leading to severe disability in 10-20 years. A clinical trial in 2006 found mild benefits from intravenous immune globulin, essentially antibodies from blood plasma. A small gene therapy trial is underway, and stem cell therapies are being considered.

—Sickle cell disease: Crescent, or sickle-shaped, blood cells block blood flow in vessels, and can lead to stroke, organ failure or death. The disease affects about 70,000 to 100,000 people in the U.S., mostly African Americans. Only one effective medication exists to help prevent deaths. But a few children and adults have been cured by blood and bone marrow transplants.

—Chronic lymphocytic leukemia : This is the most common type of leukemia, a cancer of the bone or blood, found in adults. About 15,000 people are diagnosed each year (and about 101,000 people live with it).

The new consortium’s goal is to have 200 new therapies in nine years. Many people, in seemingly isolated disease groups, are waiting.

** Taken from the Baltimore Sun **

Breakthrough at Notre Dame

Artical from the Wall Street Journal
By Amy Dockser Marcus

Researchers at Weill Cornell Medical College and the University of Notre Dame said they used drugs being tested for cancer to correct a cholesterol-storage defect in a lethal, rare disease called Niemann-Pick Type C (NPC).

The researchers found that a compound called LBH589, part of a group of drugs called histone deacetylase (HDAC) inhibitors, corrected the defect in human NPC cells in a lab setting. The LBH589 compound is being studied in clinical trials to treat several forms of cancer, including brain cancer. The idea of repurposing drugs used in more common diseases to try to treat rare conditions is an increasingly popular approach to drug development.

The finding, published this week in the Proceedings of the National Academy of Science, is considered early stage since the experiments were done in tissue culture models of NPC, a genetic cholesterol-metabolism disorder that is ultimately fatal. Typically, promising compounds are then tested in an animal model before being tried in humans. Compounds that work in cells are not always effective in animals or humans.

Paul Helquist, one of the authors of the PNAS paper and a professor of chemistry and biochemistry at Notre Dame, says the researchers are hopeful that the class of inhibitors might be useful not only in NPC disease but in other neurodegenerative disorders where lipids inappropriately accumulate in cells. He said that they would like to test the compound in a cat model of NPC disease.

The paper comes at a time when the NIH is gearing up for a clinical trial involving another promising compound, cyclodextrin, that has been tested in animal models and is being given experimentally to a small number of children. Last week, NIH director Francis Collins discussed the NIH’s NPC efforts in a webinar sponsored by the FasterCures organization.

It isn’t easy to get clinical trials going in rare diseases like NPC, which affects only an estimated 500 people world-wide. The number of patients is so small that it is difficult to attract pharmaceutical company interest. As a result, unusual partnerships are sometimes needed between patient advocacy organizations and researchers to try to drive research and trials.

The PNAS paper represents one such partnership. The research was funded in part by the Ara Parseghian Medical Research Foundation. Parseghian, the former Notre Dame head football coach, had three grandchildren who died from NPC.

Last summer, the Notre Dame College of Science dean and his wife biked over 2000 miles from Tucson — where the Parseghian Foundation is based — to Notre Dame to raise awareness about NPC. The foundation set up an endowment at Notre Dame last year to support research into and an annual scientific conference about the disease.

Among the programs, Notre Dame offers an undergraduate course at its Center for Rare and Neglected Diseases to teach undergraduates how to collect and analyze data from NPC patients. Notre Dame also has a program open to researchers who want to synthesize potential drugs for use in experiments or trials in rare or neglected diseases, including NPC.

Photo: Associated Press

Leah's story

A HEART-rending documentary about a little Fleetwood girl who captured the town’s heart was screened on prime time TV this week.

AN ITV crew spent two-and-half years filming Leah Garfitt, who suffers from the genetic illness Niemann Pick Disease Type C, and her family in Fleetwood.

Leah, who is nine years old and attends Red Marsh School, Thornton, is one of only 500 children in the world suffering from the disorder which attacks the nervous system.
It has already robbed the pretty youngster of the ability to talk and walk, and she now has numerous other problems including dementia.

And tragically, the illness is likely to cost the youngster her life before she reaches the age of just 15.

However, from Leah’s heart-breaking story film maker Chris Malone has created a film which he says is uplifting and carries a message of love, bravery and down-to earth determination.

The programme, Leah’s Dream, was broadcast on Tuesday, March 1, at 9pm on ITV1.

Manchester-based Chris told the Weekly News: “There is a sad story at the heart of it because of Leah’s illness, but in many ways it is uplifting.

“It is a love affair between a little girl and her devoted mother, Lindsey Patterson, who has to come to terms with her daughter’s illness, and the strength of their family when things are tough.

“Lindsey then also has to face up to her own illness when she is diagnosed with a brain tumour and almost dies on the operating table.”

Chris added: “The film is also about the community of Fleetwood.

“When I started filming in Fleetwood I fell in love with this place; the community is so warm and down to earth.

“Everyone seems to know Leah and there is a lot of love for her in the town.”

Well known places in Fleetwood were featured in the film, including the Ferry Cafe, the beach and promenade.

The TV film also touched on Leah’s trip to Disney World on Florida.

Funds for this once-in a lifetime trip were during a Weekly News campaign which raised an astounding £10,500 plus over 2007/8.

Fleetwood’s community responded magnificently with fundraisers and donations large and small, ensuring that Leah could enjoy the special trip while she was well enough.

Tragically, today such a trip would be impossible because Leah is not well enough.

The film starts at Leah’s seventh birthday where she is celebrating and singing along to High School musical, and follows her for the next two-and-half years.

Lindsey tells the programme about how Leah was diagnosed with Niemann-Pick as a baby after she noticed her little girl seemed tired and fragile.

Both Lindsey and Leah’s father, Michael Garfitt, carry the gene but were unaware of it.

Lindsey, of Wansbeck Avenue, Fleetwood, says in the documentary: “Not too sure what the future holds for Leah. To be honest and true, your living in limbo.”

And dad Michael says of his precious daughter: “She has taught me to care for people more, I think.

“Just to enjoy what you’ve got.”

Sturge-Weber Syndrome

What is Sturge-Weber Syndrome?
Sturge-Weber syndrome is a neurological disorder indicated at birth by seizures accompanied by a large port-wine stain birthmark on the forehead and upper eyelid of one side of the face. The birthmark can vary in color from light pink to deep purple and is caused by an overabundance of capillaries around the trigeminal nerve just beneath the surface of the face. Sturge-Weber syndrome is also accompanied by the loss of nerve cells and calcification of tissue in the cerebral cortex of the brain on the same side of the body as the birthmark. Neurological symptoms include seizures that begin in infancy and may worsen with age. Convulsions usually happen on the side of the body opposite the birthmark and vary in severity. There may be muscle weakness on the same side. Some children will have developmental delays and mental retardation; most will have glaucoma (increased pressure within the eye) at birth or developing later. The increased pressure within the eye can cause the eyeball to enlarge and bulge out of its socket (buphthalmos). Sturge-Weber syndrome rarely affects other body organs.

Is there any treatment?
Treatment for Sturge-Weber syndrome is symptomatic. Laser treatment may be used to lighten or remove the birthmark. Anticonvulsant medications may be used to control seizures. Surgery may be performed on more serious cases of glaucoma. Physical therapy should be considered for infants and children with muscle weakness. Educational therapy is often prescribed for those with mental retardation or developmental delays. Doctors recommend yearly monitoring for glaucoma.

What is the prognosis?
Although it is possible for the birthmark and atrophy in the cerebral cortex to be present without symptoms, most infants will develop convulsive seizures during their first year of life. There is a greater likelihood of intellectual impairment when seizures start before the age of 2 and are resistant to treatment.

What research is being done?
The NINDS supports a broad program of research to better understand congenital seizure disorders. This research is aimed at developing techniques to diagnose, treat, prevent, and ultimately cure disorders such as Sturge-Weber syndrome.

World Rare Disease Day-February 28th!!

Don't forget that February 28th is the 3rd Annual World Rare Disease Day.  There are an estimated 7000 rare diseases affecting 30 million people in the United States alone!!  To me these numbers were upsetting but the next number out right shocked me....out of the 30 million people affect 75% are children!  After reading this I figured that most people either know someone close or have met someone with a rare disease.  This is your chance to WEAR THAT YOU CARE.  Challenge your friends, co workers, and family to wear jeans on Monday, February 28th. Get a collection going at work or school...pay $5 to wear jeans....there are 30 million people counting on YOU!

Click here to find out where to send donations $$$$

World Rare Disease Day-Wolman Disease

What is Wolman disease?
Wolman disease is a rare inherited condition involving the breakdown and use of fats and cholesterol in the body (lipid metabolism). In affected individuals, harmful amounts of lipids accumulate in the spleen, liver, bone marrow, small intestine, small hormone-producing glands on top of each kidney (adrenal glands), and lymph nodes. In addition to fat deposits, calcium deposits in the adrenal glands are also seen.

Infants with Wolman disease are healthy and active at birth but soon develop signs and symptoms of the disorder. These may include an enlarged liver and spleen (hepatosplenomegaly), poor weight gain, low muscle tone, a yellow tint to the skin and the whites of the eyes (jaundice), vomiting, diarrhea, developmental delay, low amounts of iron in the blood (anemia), and poor absorption of nutrients from food. Children affected by this condition develop severe malnutrition and generally do not survive past early childhood.

How common is Wolman disease?
Wolman disease is estimated to occur in 1 in 350,000 newborns.

What genes are related to Wolman disease?
Mutations in the LIPA gene cause Wolman disease.

The LIPA gene provides instructions for producing an enzyme called lysosomal acid lipase. This enzyme is found in the lysosomes (compartments that digest and recycle materials in the cell), where it processes lipids such as cholesteryl esters and triglycerides so they can be used by the body.

Mutations in this gene lead to a shortage of lysosomal acid lipase and the accumulation of triglycerides, cholesteryl esters, and other kinds of fats within the cells and tissues of affected individuals. This accumulation as well as malnutrition caused by the body's inability to use lipids properly result in the signs and symptoms of Wolman disease.

Read more about the LIPA gene.

Where can I find information about diagnosis, management, or treatment of Wolman disease?
These resources address the diagnosis or management of Wolman disease and may include treatment providers.

•Gene Test: Wolman Disease

You might also find information on the diagnosis or management of Wolman disease in Educational resources and Patient support.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook

**taken from Genetics Home Reference**