3rd Annual RARE Patient Advocacy Summit

3rd Annual RARE Patient Advocacy Summit

September 11-12, 2014
Hyatt Regency Resort & Spa, Huntington Beach, California

Register today!
 

What if you could learn EVERYTHING you needed to know about being a patient advocate in just two days? What if you could learn how to be prepared, proactive, and productive in your efforts to better the lives of those with rare disease? What if you could be an advocate with the know-how to lobby congress and effect change? What if you felt you really had the ability to reach out to the largest pharmaceutical companies in the world—and form a powerful relationship to bring drugs to patients now?
 
This is what over 200 participants will be learning in-person, and over 5,000 via Livestream during the Global Gene’s 2014 RARE Patient Advocacy Summit, September 11-12, at the Hyatt Regency Resort & Spa in beautiful Huntington Beach, CA.

 

This year, participants can expect more tools, experts, and exploration than ever before. Everything has changed. The feedback we received from the last few years has been positive, but what we now understand is how much more depth our community wants and needs on topics related to their rare disease journey—and we’re determined and ready to give them that!

This year’s sessions, lead by an extraordinary team of experts, include modules on:

• Caregiving: Strategies for Staying Afloat, Presented byCaregiver Action Network
• The E-Patient Revolution, Presented by Health 2.0 andSmart Patients
• Patient-Centered Benefit-Risk Assessment, Presented byFasterCures
• Making your organization an “Unstoppable Charity”
• Lobbying at the State and Federal Level
• Transition & Transformation with Rare Disease from Adolescence to Adulthood.
• Must Have Collaborations for Successful Drug Development

Also NEW this year:

• Deep Dives - branched-off discussions that will allow small groups to interact with subject matter experts to help them go more deeply into the content of each session have been added to the agenda.
• Science Briefs -15 minute science pitches with 5 minutes of Q&A, discussing some of the most promisingInnovations in Science.

Can’t attend in person? Our new Livestream component will allow up to 5,000 advocates from around the globe to attend virtually via webcast at no cost! The event will be broadcast live with opportunities for patients to participate from afar using social media such as twitter and Facebook, using the hashtag #2014GGSummit.

 

Read more about the RARE Patient Advocacy Summit here.

To register for this event (in-person or via Livestream), please visit: http://globalgenes.org/events

Utah Hemp Extract Registrant #1

This morning, Bertrand became the first person in the state of Utah to receive a Hemp Extract Registry Card.

While Bertrand may not receive CBD oil for quite some time, we wanted to show our support for the new law on the very first day.  

The only time I could fit a trip down to the Utah Department of Health was at 9:45am, after school bus pick-up, camp drop-off and some errands, but before school bus drop-off, camp pick-up, and a doctor's appointment.  (And, let's not forget, nursing baby.)

Since the Office of Vital Records opens at 8AM, we did not expect to be the first in line.

There was a bit of confusion from some of the staff when we first arrived, but things were quickly straightened out.  

Since all of our paperwork was in order ahead of time, getting the card only took 30 minutes (and should be faster for subsequent registrants).

The Hemp Registry Instructions on the Utah Department of Health website were very thorough and easy to follow.

The Department of Health is accepting applications via mail or in-person.  

For the first week only, walk-ins are welcome, but appointments will be required in the future.

Please see the Utah Department of Health website for more information.

I broke my no-selfie rule to show Bertrand one of the kind registrars at the Dept. of Health, Leisa Finch, who is helping kids like him get access to these cards.  

A big hip hip hooray for the state of Utah, our representatives and senators, and the fantastic folks at Hope 4 Children with Epilepsy who made this all possible!

Seizure Smart-er

Matthew and I attended the Epilepsy Association of Utah's Seizure Smart Conference.  Given Bertrand's impending travel, we could only attend a few sessions.  The topics were cannabidiol extract, new legislation, and the genetics of epilepsy.  It was an informative and motivating conference.  We were glad we went!  The folks at EAU did a fantastic job, as did all of the speakers.

Look Niki!  We missed you.  You should have been here!  :)

The amazing Heather Jackson with The Realm of Caring.

The fantastic Jennifer May with Hope 4 Children with Epilepsy.

Advances in Gene Editing

Targeted genome editing in human repopulating haematopoietic stem cells

• Pietro Genovese,
• Giulia Schiroli,
• Giulia Escobar,
• Tiziano Di Tomaso,
• Claudia Firrito,
• Andrea Calabria,
• Davide Moi,
• Roberta Mazzieri,
• Chiara Bonini,
• Michael C. Holmes,
• Philip D. Gregory,
• Mirjam van der Burg,
• Bernhard Gentner,
• Eugenio Montini,
• Angelo Lombardo
• & Luigi Naldini

• Affiliations
• Contributions
• Corresponding author

Nature

 

(2014)

 

doi:10.1038/nature13420

Received

 

02 August 2013 

Accepted

 

29 April 2014 

Published online

 

28 May 2014

Abstract

• Abstract• 
• References• 
• Author information• 
• Extended data figures and tables• 
• Supplementary information

Targeted genome editing by artificial nucleases has brought the goal of site-specific transgene integration and gene correction within the reach of gene therapy. However, its application to long-term repopulating haematopoietic stem cells (HSCs) has remained elusive. Here we show that poor permissiveness to gene transfer and limited proficiency of the homology-directed DNA repair pathway constrain gene targeting in human HSCs. By tailoring delivery platforms and culture conditions we overcame these barriers and provide stringent evidence of targeted integration in human HSCs by long-term multilineage repopulation of transplanted mice. We demonstrate the therapeutic potential of our strategy by targeting a corrective complementary DNA into the IL2RG gene of HSCs from healthy donors and a subject with X-linked severe combined immunodeficiency (SCID-X1). Gene-edited HSCs sustained normal haematopoiesis and gave rise to functional lymphoid cells that possess a selective growth advantage over those carrying disruptive IL2RG mutations. These results open up new avenues for treating SCID-X1 and other diseases.

A Year at Base Camp

Bertrand's diagnosis of N-glycanase deficiency was officially rendered one year ago.  And we were jubilant! ...for a little bit.  Since then, I've half-jokingly referred to receiving the diagnosis as "reaching base camp".  Yes, it was an amazing achievement, but we've got a long way to go before reaching the summit.  I've spent a lot of this past year exhausted from simply thinking about the effort that lays ahead.

I am still reeling from the loss of Hannah, Bertrand's little girlfriend, who suffered from Gaucher's disease type 2/3. Hannah was the last child of our original blog/support cohort.  Losing Hannah essentially left Bertrand the last man standing.  The sensation was unsettling, to say the least.  Hannah was a fighter, and you couldn't find better parent-advocates than Carrie and Robert, her parents.  And yet, she still died.  What hope did that leave for Bertrand?

Hannah had a diagnosis.  And a community with foundations and awareness.  And researchers with funds and support from pharmaceutical companies.  And existing (if imperfect) enzyme treatments with FDA approval.  And that was not enough.

Bertrand had NONE of that--not even a diagnosis--a year ago.

If we look at history, first patients are usually dead patients.  They never benefit from the contributions they make to science.

But somehow, against the odds and our better judgement, we have hope.

So, how do you climb a mountain?  You take the next step.

We're now very focused on building a community, and though we can't release any specifics, we can reveal that seven additional cases of NGLY1-deficiency have been confirmed over the past year.

It really is a brand new disease: from 0 cases to 8 in one year.

We can't let ourselves get overwhelmed by the prospect of research or raising research funds or fighting for FDA approval or dealing with side-effects or rehabilitating Bertrand (should a treatment/cure work, that would be a mountain in and of itself).

We just have to take the next step.

We will continue to work with researchers at Sanford-Burnham and an ever-expanding team of scientists to understand N-glycanase deficiency and identify potential treatments.  We will continue to explore the scientific literature.  And we will work on building an NGLY1 patient registry and community (http://www.ngly1.org).

We will climb this mountain.

Watch out, Summit.  Here we come.

First Gene Therapy Approved!

We will be watching the 2013 commercial roll-out of Glybera very, very closely.

First Gene Therapy Approved by European Commission

Amsterdam, The Netherlands – November 2, 2012 – uniQure announced today it has received approval from the European Commission for the gene therapy Glybera® (alipogene tiparvovec), a treatment for patients with lipoprotein lipase deficiency (LPLD, also called familial hyperchylomicronemia) suffering from recurring acute pancreatitis. Patients with LPLD, a very rare, inherited disease, are unable to metabolize the fat particles carried in their blood, which leads to inflammation of the pancreas (pancreatitis), an extremely serious, painful, and potentially lethal condition. The approval makes Glybera the first gene therapy approved by regulatory authorities in the Western world.

“Glybera’s approval means LPLD patients, for the first time, have a medical treatment option for a very complex and severe disease,” said Professor John Kastelein of the Department of Vascular Medicine at the Academic Medical Center of the University of Amsterdam, the Netherlands. “LPLD leads to acute and recurrent pancreatitis attacks, and in many patients causes early onset diabetes and cardiovascular complications. This therapy will have a dramatic impact on the lives of these patients. Currently their only recourse is to severely restrict the amount of fat they consume. By helping to normalize the metabolism of fat, Glybera prevents inflammation of the pancreas thereby averting the associated pain and suffering and, if administered early enough, the associated co-morbidities.”

As part of the approval, patients will receive treatment with Glybera through dedicated centers of excellence and by specially trained doctors. uniQure will also build a patient registry to further improve the understanding of this devastating, under-researched disease and the effects of Glybera treatment. Marketing Authorisation covers all 27 European Union member states. uniQure is preparing to apply for regulatory approval in the US, Canada, and other markets.

“The final approval of Glybera from the EC marks a major step forward in making gene therapies available not only for LPLD but also for a large number of rare diseases with a very high unmet medical need,” says Jörn Aldag, CEO of uniQure. “The EC’s approval is an important validation of our innovative product platform and offers strong support for our other advanced development programs, which focus on acute intermittent porphyria, Sanfilippo B, hemophilia B and Parkinson’s disease.”

About Glybera®
uniQure has developed Glybera as a therapy for patients with the genetic disorder lipoprotein lipase deficiency, an orphan disease for which no treatment existed. The disease is caused by mutations in the LPL gene, resulting in highly decreased or absent activity of LPL enzyme in patients. This enzyme is needed in order to break down large fat-carrying particles that circulate in the blood after each meal. When such particles, called chylomicrons, accumulate in the blood, they may obstruct small blood vessels. Excess chylomicrons result in recurrent and severe acute inflammation of the pancreas, called pancreatitis, the most debilitating complication of LPLD. Glybera has orphan drug designation in the EU and US. LPL Deficiency affects 1-2 persons per million.

Glybera has been tested in three interventional clinical studies conducted in the Netherlands and in Canada, in which a total of 27 LPLD patients participated. In all three clinical trials, Glybera was well tolerated, with no relevant safety issues observed. Data from these clinical trials indicate that a single dose administration of Glybera resulted in a long-term biological activity of the LPL protein. For further information on LPLD visit www.lpldeficiency.com.

Lipoprotein lipase is a key ‘first step’ enzyme in the metabolism of lipoproteins following fat intake with diet. In clinical studies a transient reduction in triglycerides for up to 12 weeks in individual patients could be observed. Furthermore, Glybera allows expression of the LPL protein in injected muscle which is reflected by the improvement of postprandial chylomicron (CM) metabolism observed in a small subset of patients. Glybera (alipogene tiparvovec) contains the human lipoprotein lipase (LPL) gene variant LPLS447X in a vector. The vector comprises a protein shell derived from adeno-associated virus serotype 1 (AAV1), the promoter, a posttranscriptional regulatory element and AAV2 derived inverted terminal repeats.

Glybera is indicated for adult patients diagnosed with familial lipoprotein lipase deficiency (LPLD) and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions. The diagnosis of LPLD has to be confirmed by genetic testing. The indication is restricted to patients with detectable levels of LPL protein.

The most commonly reported adverse reaction is pain in extremity occurring in approximately one third of patients. Given the small patient population and size of the cohorts, observed adverse reactions do not provide a complete perspective on the nature and frequency of these events.

About uniQure
uniQure is a world leader in the development of human gene based therapies. uniQure product pipeline of gene therapy products in development comprise hemophilia B, acute intermittent porphyria, Parkinson’s disease and SanfilippoB. Using adeno-associated viral (AAV) derived vectors as the delivery vehicle of choice for therapeutic genes, the company has been able to design and validate probably the world’s first stable and scalable AAV manufacturing platform. This proprietary platform can be applied to a large number of rare (orphan) diseases caused by one faulty gene and allows uniQure to pursue its strategy of focusing on this sector of the industry. uniQure's largest shareholders are Forbion Capital Partners and Gilde Healthcare, two of the leading life sciences venture capital firms in the Netherlands. Further information can be found at www.uniqure.com.

2012 Conference on Rare Diseases and Orphan Products

U.S. Conference on Rare Diseases and Orphan Products

Register By October 1 For Early Bird Rate!

Join patient advocates, drug and device industry leaders, researchers, government partners and investors at this major conference to address together "Shaping the Future Now" for rare diseases and orphan products.  Sponsored by NORD and DIA, with major input from FDA and NIH, this event will include general and breakout sessions with three themes:  policy, research and regulation, and special challenges.
The 2nd annual U.S. Conference on Rare Diseases and Orphan Products will take place October 22-24 in Washington DC. Everyone is welcome, and the program should be of particular interest to:

• Researchers from academia and drug and device companies
• Patient organizations and those interested in creating one
• Senior managers from drug and device companies interested in rare diseases
• Investors focused on the future of orphan product development
• Policy experts who are concerned about federal or state policies that affect patients with rare diseases
• Providers of services to the rare disease community, including insurance providers and healthcare professionals
• Government officials responsible for rare disease research and orphan product oversight

Online Registration Is Open Now!

A full description of the conference and online registration are available now.  Register by October 1 for the Early Bird rate.  Topics and speakers will include:

• Impact of FDASIA on Orphan Product Development (Andrew J. Emmett, MPH, Managing Director, Science and Regulatory Affairs, BIO; Cassie A. Scherer, JD, Policy Advisor, Office of the Center Director, CDRH, FDA)
• Investing in Orphan Products: Is the Environment Getting Better or Worse? (session chaired by Thomas M. Burton, JD, Staff Reporter, The Wall Street Journal)
• Special Challenges in Rare Diseases (John J. Castellani, President & CEO, PhRMA)
• Well-Designed & Well-Conducted Clinical Trials (session chaired by Gayatri Rao, JD, MD, Director, FDA Office of Orphan Products Development)
• The New Relationship With the Patient Community (session chaired by Jayne C. Gershkowitz, Senior Director, Patient Advocacy & Public Policy, Amicus Therapeutics)
• TRND and Translational Development (Christopher P. Austin, MD, Scientific Director, NIH Center for Translational Therapeutics, National Center for Advancing Translational Sciences)
• Endpoint Development (session chaired by Anne R. Pariser, MD, Associate Director for Rare Diseases, Office of New Drugs, CDER, FDA)
• Facing the Crisis in Biomedical Innovation: A Venture Investor's Perspective (Jonathan S. Leff, MBA, Managing Director, Warburg Pincus)
• Research and Regulation (Robert M. Califf, MD, MACC, Vice Chancellor for Clinical and Tanslational Medicine; Director, Duke Translational Medicine Institute; Duke University School of Medicine)

At a Critical Moment in Time: Bringing All Stakeholders Together

With a major new law (the FDA Safety and Innovative Act) soon to be implemented, this forward-looking conference brings together all stakeholders to "Shape the Future Now" for rare diseases and orphan products.
The conference is co-sponsored by the National Organization for Rare Disorders (NORD), the voice of 30 million Americans with rare diseases, and the Drug Information Association (DIA), a neutral, nonprofit, global professional association for those working in discovery, development and management of pharmaceuticals, medical devices and related products.
Collaborators include Duke University School of Medicine, EURORDIS (Rare Diseases Europe), the Food and Drug Administration (FDA) and the National Institutes of Health (NIH).

Sanford-Burnham Medical Research Institute

We're headed to Sanford-Burnham Medical Research Institute (SBMRI) this week. SBMRI is where a team, headed by Dr. Hudson Freeze, has been working to understand Bertrand's genetic disorder and find a treatment. We're excited to hear details on the progress they have made in helping Bertrand and other children like him!

Enzyme Treatment for N-Glycanase Disorder

Just one of Genzyme Corporation's patents related to the manufacture of N-glycanase.

Prepare to get the chills.

Most enzyme disorders require years and millions of dollars in Research and Development to develop an enzyme replacement treatment.

Not in this case.

N-glycanase.  Is.  Already.  Manufactured. 

 ...for laboratory use only.

As Bertrand would have you know, N-glycanase is a very important and useful enzyme. So much so, that it is already used extensively in the research and creation of other enzymes and pharmaceuticals.

Several patents related to the manufacture of N-glycanase (including the one above) were issued to Genzyme Corporation in the early 1990s.

Genzyme Corporation is a world leader in biotech, rare disease, and pharmaceutical development.

It is the perfect company to translate N-glycanase from a lab product to a drug for human use.

******************

What about the dreaded FDA approval process?

Won't it be years before Bertrand could get this treatment?

In February of this year, the FDA modified their policy for expanded access (more commonly referred to as "compassionate use").

The FDA will grant permission within 30 days of receiving an application for expanded use of Investigational New Drug (IND) by an individual.

"It is intended to improve access to investigational drugs for patients with serious or immediately life-threatening diseases or conditions who lack other therapeutic options and who may benefit from such therapies."

Yup.  Bertrand qualifies.

******************

What do we need?

(1) A doctor comfortable with overseeing Bertrand's experimental treatment.
In case you're wondering: how hard is it to find a doctor who trained as a pediatrician, with a specialty in clinical biochemical genetics, with a research focus on metabolic disorders, specifically congenital disorders of glycosylation? The answer is "very".

(2) Genzyme's cooperation with developing a human N-glycanase treatment.
We're waiting to hear back from a Genzyme representative.

(3) FDA expanded access approval.
This actually appears to be the easy step.  We need the doctor and Genzyme's help first.

******************

A few more points...

Confirming patient #2 with an N-glycanase disorder would add significant grease to the wheels.
(Fingers crossed.)

And like many enzyme replacement treatments, N-glycanase would not cross the blood brain barrier.  However, the brain is among the organs with the least use of N-glycanase, so Bertrand could still experience substantial benefit.  Also, there are options to circumventing the BBB worth exploring.

Things to think about...

Today, Bertrand had his first appointment with an epileptologist in Utah. We're waiting to hear back from scheduling for a 2 day overnight EEG. The doctor also left us with two new treatments to research and think about:

• Banzel (Rufinamide)
• High-Dose Valium Protocol

Next steps will be taken based on the EEG findings.

Naturopathic Treatment Plan

From top left: Nordic Naturals cod liver oil, children's chewable multivitamin, whey protein powder, detox pill, vitamin E (mixed tocopherols) pill, lecithin granules, vitamin A (beta-carotene form) drops, oxicell (glutathione and superoxide dismutase) topical cream.

This morning, Bertrand woke up with his glands (tear ducts, eyelids, nose, skin pores) on overdrive and pooping a lot. With Bertrand, poop is always a good sign. This means he was in a GREAT mood: happy and interactive. Also, no (*knock on wood*) seizures.

DUE DILIGENCE. Bertrand's naturopathic treatment does not replace his conventional medical treatment. He remains on the medications lamictal (25mg x2), depakote (250mg x2), actigall (180mg x3) and carnitor SF (450mg x2). And, he'll remain on these medications unless his neurologist and gastroenterologist say otherwise. (And, we will subject naturopathic recommendations to the same experimental and observational scrutiny we apply to any other.)

This initial naturopathic treatment plan is just that: initial. He will not remain on these high doses of vitamins and supplements long-term. In 3 weeks, he has a follow-up to adjust this treatment plan and go over test (lead, food allergy, microbiology) results.

In researching the individual items of the treatment plan, I am most skeptical/concerned about the "detox" supplement aimed at liver detoxification. We will be watching Bertrand very closely for any adverse signs. The remaining treatment plan items (supplements, craniosacral therapy, etc.) cause harm only to our pocket book.

As far as tests go, there were two blood tests and one stool test. The stool test is called a "microbiology". From my understanding, it is used to measure the levels and identify the types of both good and bad bacteria in the digestive tract. The blood tests included one for lead (self explanatory) and one for food allergy.

FOOD ALLERGIES. I've asked Bertrand's doctors about food allergies before at the encouragement of little John's mom. Also, I know Bertrand's IgE and IgG are elevated. This can be due to infection or allergies. For the most part, his doctors have always dismissed this as "he's probably dealing with a cold". He also had an EGD earlier this year which showed no signs of Celiac or food allergies.

But, Bertrand's upper respiratory tract always sounds congested. Every single doctor checks him out because of it. But, upon listening to his lungs, which are clear, they just scratch their heads and say he is fine. Well, the naturopathic doctor doesn't think this is "fine" and I agree. That doesn't mean I'm convinced it is allergies, but something is causing Bertrand's raspiness, snoring, and rough breathing issues. I hope we can get to the bottom of this.

The naturopathic doctor felt that Bertrand should be tested for food allergies because he sees upper respiratory issues commonly with dairy allergies. Yes. DAIRY. As in 90% of Bertrand's current diet. And, I'm pretty sure it's just another IgG/IgE test which will almost certainly come back elevated, because they always do.

So, what to do? Well, like anything else, if it is indicated, we'll give it a shot. Compared to ACTH injections, the ketogenic diet, and all the other torture he's been through, cutting out Bertrand's dairy would be a cinch.

Utah Natural Medicine

Bertrand's new treatment plan which I'll detail tomorrow.

Today was Bertrand's first appointment with Matthew Burnett, a naturopathic doctor at Utah Natural Medicine. In many ways, it was just like any other doctor's appointment: there was an obscene amount of paperwork, an exam, some blood work (you know Bertrand can never escape blood work)... But, something remarkable also happened: Dr. Burnett actually read the huge stack of papers I filled out! I don't think that has EVER happened before! (Is that sad or what?) I wish I'd taken more time and care with the answers, but I'm a bit jaded when it comes to medical forms. I wasn't about to get a cramp in my hand for no good reason.

I'm not going to lie. It was nice.

Dr. Burnett actually read what I wrote and listened when I spoke. He also spoke to Bertrand and was respectful--talking through the exam with Bertrand and including him as much as possible. (That's pretty much the straightest path to cool points in my book.)

All the weird symptoms*--which I'd mentioned to other doctors since Bertrand's birth but been assured were "normal" or "normal for a special needs child"--got dredged up. And FINALLY someone agreed with me that they were NOT NORMAL and it was not acceptable to ignore these symptoms--to "sweep them under the rug"--because Bertrand is a special needs child.

Hallelujah? Rejoicing? Well, maybe I'll admit to a little happy dance, but, like I mentioned above, I am kinda jaded when it comes to the medical establishment--no matter how granola. If/when I see results, then we'll talk. But, wow. I'm not sure if I can't believe it's come to this? Or if I can't believe it took me so long?

We've put Bertrand through hell, but all this guy wants is for Bertrand to get a finger prick, get some head massage and drink some smoothies**? I'm down with that. And, for the record, so is B--he now likes smoothies. :)

---------------------------------------------------------

*The weird symptoms include but aren't limited to the lack of tears, the blue sclera of his eyes, repeated styes, cold hands/feet, constipation, and more.

**The terms head massage & smoothies, for craniosacral therapy, detoxification and protein, vitamin and mineral therapy, are a gross simplification, but I don't think Bertrand cares enough to tell the difference.

A Family's Perspective

Our family at this time last year, with Bertrand in the midst of his ACTH treatment.

Our family is participating in a research study being conducted by Duke University scientists: "Genomic Study of Developmental Delay and Congenital Anomalies of Unknown Etiology".

This is a landmark study that's using the full genomic sequencing of our family to determine the genetic nature, if any, of Bertrand's condition.

We were asked to provide a family perspective, on why we chose to participate in the study and what we hope to get out of it. This was our response:

Uncertainty inflicts a crippling emotional tax on parents as they watch their child suffer from an undiagnosed disease.

Can you imagine the unyielding second-guessing over whether your child's agony was your own fault or an act of chance?

Can you imagine wanting more children, yet never knowing whether it would be safe or responsible to have them?

Can you imagine being ashamed at your own jealousy over parents whose children have a terminal yet *named* disorder?

Can you imagine feeling that you can't do the right thing for your child because the information you need seems hopelessly beyond your grasp?

We haven't had to imagine. This is our reality.


We had taken our son Bertrand to dozens of hospitals and dozens of specialists.

His blood has been drawn so many times for so many tests that the scarred and needle-worn veins in his arms now offer no more than droplets.

We had given up hope of ever finding a diagnosis for our son.

The hypothesis has been that he was a de novo mutation, and likely the only one of his kind--firmly beyond the reach of modern medical diagnostics.


When Duke contacted us about the chance to participate in this study, we realized that this was the cutting edge science necessary to push modern medicine out to our son.

We know that the outcome of this study will not cure our child.

But, there is good reason to believe that it is our best and only chance at getting the information we need--the information to bring closure, peace of mind and the knowledge that we as parents are pursuing the best possible treatment for our child.

Botox, phenol or surgery! Oh, my!

Bertrand slacks-off while Mama changes his sheets. ;)

His depakote dose was increased to 250mg today.

This morning, Bertrand had a fantastic occupational therapy session during which his therapist summarized that B's biggest improvement the past few weeks has been in attitude. He is happy, engaged, willing to initiate, not as prone to overstimulation, persistent and forgiving. He hasn't really had any motor breakthroughs yet but, thanks to his positive attitude, she feels certain that breakthroughs will come.

That was followed-up by an appointment with Bertrand's rehabilitation doctor. Bertrand's right hip is subluxated between 50 and 60%. This is due to spasticity in the right adductor muscle because Bertrand doesn't stand. (As the old saying goes: if you don't use it, you lose it.) If Bertrand ever wants to crawl, walk, use his right hip, or even just not be in pain, we need to keep it from further subluxation. This poses a parent dilemma.

To deal with the subluxation, we have to deal with the spasticity or end-up in surgery. The surgery is a major one with a substantial recovery time. The other standard options for dealing with spasticity are botox and/or phenol injections. We know many kids who successfully receive them. Each has their pros and cons. The doctor feels that phenol would be best in Bertrand's case. Both of these injections will hurt. Both will wear off.

[And, in large quantities, both have killed millions of people historically. *Shudder*]

Obviously, I don't want Bertrand to lose his option to walk or crawl someday, or to be in pain, or for him to undergo a major surgery (with a long recovery time) to fix a problem that could've been prevented less invasively, such as through an injection.

So, I made Bertrand's phenol injection appointment for Friday of next week.

But something just doesn't feel right--call it my mommy-spidey sense.

Bertrand's subluxation hasn't worsened in 6 months despite a broken leg.

I think I want to give therapy a chance to work first.

I want to give Bertrand, with his new can-do attitude, a chance to do something without another painful intervention.

I know this will take dedication from more than just me.

It will take Bertrand's Daddy, and his Titi Saby, and his Nana, and his therapists, and his team at school... but Bertrand deserves a trial period.

Bertrand sees his orthopedist again in July. He'll get new hip x-rays then. That means just 4 months to get him standing at least 2 hours a day and to keep that hip from getting worse.

I believe he can do it.

Am I crazy?

We'll see in 4 months.

Stem Cell Infusion Schedule!

Image from http://stemcellumbilicalcordblood.com/

Everything is officially a "go" for Bertrand's stem cell infusion! CBR, the company we stored Bertrand's cord blood with, has transferred his blood to Duke University and the Pediatric Stem Cell Transplant Program at Duke sent our schedule today (see below). We just bought our plane tickets! This infusion will likely do nothing for Bertrand but we have to try it given the successes there have been with other forms of brain injury.

It has been a pleasure talking you about your decision to come to Duke for Bertrand’s reinfusion of autologous banked cord blood cells. We look forward to see you all again. A schedule is listed below for Bertrand’s appointments here at Duke University Medical Center.

Monday, August 23, 2010

8:15am Please check Bertrand in at the McGovern-Davison Children’s Health Center (CHC), 4th Floor, which is our clinic. Bertrand will have vital signs taken, be weighed, measured, and have blood work drawn. The blood work will be drawn by a phlebotomist. The phlebotomist will attempt to collect the blood samples with minimal needle sticks. If the blood cannot be obtained by the phlebotomist, please have the phlebotomist see Colleen McLaughlin, Pediatric Nurse Practitioner, about obtaining the blood samples. Bertrand will also have a head circumference done (his head measured).

Colleen McLaughlin, Pediatric Nurse Practitioner, will take a detailed medical history and perform a physical exam on Bertrand as well as consent for his reinfusion.


Tuesday, August 24, 2010

12:15pm Please check Bertrand in at the McGovern-Davison Children’s Health Center (CHC), 4th Floor. Bertrand will be weighed, measured and have vital signs taken. After check in you are welcome to go to the gift shop located on the 1st floor of the CHC or the cafeteria in the main hospital for snacks. During this time Bertrand’s unit will be processed in our lab. There will be about an hour wait time for unit processing.

Bertrand will be seen by Dr. Kurtzberg after which time an IV will be placed by Dr. Kurtzberg so that Bertrand will be able to receive his cells. It is easier to start the IV, if you have made sure that Bertrand is well hydrated. Bertrand will be monitored in a room in the Valvano Day Hospital. You will be able to be with Bertrand the entire time. You may eat in Bertrand’ room if you wish. He will receive IV fluids for several hours after the reinfusion of cells. Bertrand will be seen by Dr. Kurtzberg prior to discharge.

Please bring Bertrand’ favorite toys to this appointment.

Wednesday, August 25, 2010

Please call Colleen McLaughlin at (919) 668-2657 to let her know how Bertrand did overnight. If all goes as anticipated you may return home.

We look forward to seeing you at Duke. Please have a safe trip to Durham.

Kit-Based Cord Blood Program Gives Moms New Options for Donation

By Duke Medicine News and Communications

A new kit-based umbilical cord blood pilot donation program under way at Duke University Medical Center could significantly expand options for mothers who want to donate their baby’s cord blood to a public bank.

“Right now, there are fewer than 200 hospitals in the United States designated as collection sites for mothers who want to donate their baby’s cord blood to a public bank,” says Joanne Kurtzberg, MD, professor of pediatrics at Duke and director of the Carolinas Cord Blood Bank (CCBB), a public bank. “We simply need more. Cord blood cells are increasingly seen as a valuable resource, and we are seeing a pressing need for more cord blood donation, especially among Asian and African-American mothers and those with mixed ethnic backgrounds.”

Umbilical cord blood stem cells, normally discarded after birth, have the ability to grow and develop into various types of cells throughout the body. They can be harvested after birth and stored for future transplantation in patients with many types of cancer and blood disorders, and increasingly, in other diseases as well.

In addition to Duke, two other sites are participating in the program, the M.D. Anderson Cancer Center in Houston and the Texas Cord Blood Bank in San Antonio. All three sites are members of the National Cord Blood Inventory’s public banking network of the C.W. Bill Young Cell Transplantation Program and are coordinating their efforts through the National Marrow Donor Program (NMDP).

Donated cord blood will be listed on the NMDP’s Be The Match Registry and will be made available to patients with diseases that can be treated with transplantation.

“Research shows that many more mothers would donate their baby’s cord blood if given the opportunity,” says Michael Boo, chief strategy officer for the NMDP. “This pilot program may uncover a successful way to allow more expecting parents to donate, providing hope to more patients.”

Expectant mothers interested in donating cord blood through the program need to call one of the sites at least six weeks before their baby is due. Eligible donors must be 18 years old or older and be pregnant with a single baby. A coordinator will pre-screen applicants to see if they are eligible to become donors, asking questions about age and any history of HIV, cancer, hepatitis, malaria, organ or tissue transplant, sexually transmitted diseases, and tattoos and body piercing.

There is no charge to the mother for the kit or for donating her cord blood through the kit program.

Participants need to inform their physician or midwife of their intention to donate through the kit program. The physician or midwife must successfully complete an online training and certification in cord blood collection through the NMDP.

Participating moms will be sent a kit prior to their due date and will take the kit to the hospital upon admission for delivery. The doctor or midwife will collect the cord blood after the baby is born. The cord blood must be packed and shipped back to one of the three participating sites and must be received within 40 hours of the infant’s delivery.

The kit itself is specially designed to protect the cord blood in transit. Duke’s bright red box is temperature-controlled and contains an informed consent, a medical history questionnaire, and forms to be filled out at the hospital. It also contains everything needed for the cord blood collection, plus additional vials to store some of the mother’s blood that will be tested for infectious disease.

“We are enthusiastic about this program because if it successful, it could potentially be expanded to additional hospitals nationwide,” says Kurtzberg.

Kurtzberg, who is also director of Duke’s Pediatric Blood and Marrow Transplant Program, is internationally recognized for her trailblazing work in cord blood stem cell therapies. She provided care for the first person ever to receive a cord blood transplant and was the first in the world to perform an unrelated cord blood transplant.

Mothers interested in donating their baby’s cord blood to a participating public bank may contact the Carolinas Cord Blood Bank Public Kit Collection Program by calling 919-668-2071 (daytime only).

To reach the M.D. Anderson coordinator, call 713-563-8000.

To reach the Texas Cord Blood Bank coordinator, dial 800-292-5534; option 7.

For more information about public cord blood donation and the National Marrow Donor Program, visit BeTheMatch.org or call 1-800-MARROW-2.

Hear Dr. Kurtzberg talk about cord blood and the kit program

HIV-based gene therapy effective for a lysosomal disorder

Scientists in France have used a disabled HIV virus to deliver corrected genetic code into the blood of X-linked adrenoleukodystrophy patients for the first time. Gene therapy, in which a patient's DNA is modified to correct genetic defects, has long been a holy grail of medicine, but it has been difficult in practice. To make gene therapy work, you have to replace the DNA in every cell that's affected. The problem with this is that the process of modifying all those cells too quickly can easily kill the patient. One mechanism for inserting new DNA is to use a modified virus [since a virus is little more than parasitic syringe for DNA], but with that route, it's important to control the rate at which the virus spreads. This is encouraging news, because if HIV proves a safe and effective carrier for new genetic material, it could be applicable to a range of diseases hypothetically treatable with gene therapy.

Ruled Out: Lesch-Nyhan Disorder

We got the Metabolic Clinic Medical Report in the mail today. Included with the report were some lab results I hadn't seen yet--in particular the uric acid test results. Bertrand's uric acid came back normal, which discounts another dreadful disease called Lesch-Nyhan Syndrome. So, it's back to the drawing board--or rather--back to medical imaging.

The MRI next week (4/8/09) will really be able to tell us what direction to move in. MRI gives information about the structure of the body (the distribution of water and fat). With the MRI he'll also be getting a MR spectroscopy and a MR angiography. The Magnetic Resonance Spectroscopy is used to obtain biochemical information. The Magnetic Resonance Angiography is used to generate images of the arteries.

A procedure that, while not for a diagnosis, may help guide Bertrand's treatment is a Lumbar Puncture (LP)--also known as a spinal tap. As mentioned in a prior post, Bertrand's prolactin levels were elevated. The movement disorder portion of his presentation could be caused by too much neurotransmitter--which is treatable. I am certain that reducing his involuntary movements would decrease Bertrand's frustration and improve his quality of life.

Some Days Are Better Than Others

I am proud that Matthew posted yesterday, because I could barely breathe much less think clearly enough to write. Now, on a beautiful spring day and with a bit of sleep, I can say, "Hey! At least it is not mitochondrial!" The general impression we are receiving from our specialists at the University of Utah is that Bertrand is too old for the cord blood transplant. As parents, we still HAVE to see if that's an viable option--it would be his best chance for long term survival.

Perhaps it is naive, but we believe that as long as we can stop the damage (partcularly brain damage) in its tracks and get his body to start producing its own enzymes, maybe stem cell therapies can repair some of his brain damage in the near future. Bertrand needs to live long enough for that to even be possible.

There is a company called Aldagen now making stem cell treatments to help repopulate the cells for children with inherited metabolic diseases. There is currently a clinical trial accepting patients up to age 16, but we need a diagnosis first. (A clinical trial would be nice since they may cover some of our travel and related expenses.) This Aldagen therapy could potentially help kids with the following:

• Hurler Syndrome (MPS I)
• Hurler-Scheie Syndrome
• Hunter Syndrome (MPS II)
• Sanfilippo Syndrome (MPS III)
• Maroteau-Lamy Syndrome (MPS VI)
• Krabbe Disease (Globoid Leukodystrophy)
• Metachromatic Leukodystrophy (MLD)
• Adrenoleukodystrophy ALD and AMN)
• Sandhoff Disease
• Tay Sachs Disease
• Pelizaeus Merzbacher (PMD)
• Neiman-Pick Disease
• Alpha-mannosidosis

To help with diagnosis Bertrand got more labs done today. At the University of Utah laboratory he is getting the following tests:

• Biotinidase enzyme (retest)
  
• Uric acid
• Prolactin
• Ceruloplasmin
• Copper

At the Baylor College of Medicine laboratory he is getting the following tests:

• Fucosidosis
• Krabbe Disease
• Mannosidase Deficiency
• Tay-Sachs Disease & Sandhoff Disease

His doctors seemed to think it would be better to have the tests sent to Baylor over Mayo this time due to better controls and increased specificity. (Mayo botched the thin layer chromatography on the last oligosaccharide test.)

So at the UofU lab today, they drew a LOT of blood (stuck him in both arms since he clots so quickly), and then called us at home to come back. They hadn't drawn enough blood! So we went back and they had to draw from his hand. It was a *rough* morning.

Even though time in a lab is not the most cinematic, it has been such a large part of Bertrand's life, we had to capture it somehow. We were able to capture part of the blood draw on our new, fabulous VIDEO CAMERA! An early Mother's Day gift from my father, and I couldn't be happier! We've gone a little camera crazy today--taping everything. :)

Our day has also been filled with making preparations. One of our dog's, Mr. Wang, will be leaving this Friday to stay with my mother in Kentucky. This is in preparation for our travel to North Carolina and Bertrand's potential transplant recovery. (We're being hopeful.) Our other dog, Penny, will likely stay with a neighbor or my in-laws.

We're waiting to hear back from: (a) Samson-Fang on a quicker MRI, (b) our case manager at Blue Cross Blue Shield on out-of-state approval, and (c) Kurtzberg on getting a work-up at Duke.

Bone Marrow Transplant: LOOKING FOR DONOR!

We need to start looking for possible bone marrow donors for Bertrand. This is on the chance that his lysosomal condition is one of those which can be treated with such a transplant. If by some miracle we have a matching donor lined-up (next to impossible) we can get the transplant in a matter of weeks.

PLEASE consider getting checked! The closest match is usually a sibling, but Bertrand doesn't have any. And, neither Matthew nor I may be an acceptable match. :'(

"Doctors look for a donor who matches their patient's tissue type, specifically their human leukocyte antigen (HLA) tissue type. HLA are proteins — or markers — found on most cells in your body. Your immune system uses these markers to recognize which cells belong in your body and which do not. The closer the match between the patient's HLA markers and yours, the better for the patient."
--National Marrow Donor Program

The National Marrow Donor Program has a great page on the ins and outs of HLA Matching and a list of Donor FAQs.

We'll be in touch with Bertrand's doctors this week for many things, including determining his HLA.