80% of Rare Diseases are Genetic

80% of the 7,000 Rare Diseases are genetic in nature.   80-are-genetic---February-is-Rare-Disease-Month

While most rare diseases show symptoms early in life, many are later onset diseases because our genetics are always with us.

Genetic inheritance patterns can vary from single gene autosomal recessive (like MLD) where 50% of offspring are carriers, 25% are affected, and 25% are free of the bad genes entirely … to autosomal dominant where 50% of offspring have the disease … to several forms of X-linked where which parent is affected and the sex of the child determine the inheritance pattern … or inheritance can be a more complicated multifactorial pattern that includes genes and environment … and there are mitochondrial inheritance patterns as well.  Learn more about forms of inheritance here.

Autosomal Recessive

It is important to note that carriers, while most often not sick, can pass along carrier or affected status if their spouse/partner is also a carrier.  Very rare diseases like MLD have a frequency of 1 in 40,000 births, but note this equates to 1 in 100 of the general population being a carrier.  That’s one carrier in every 3 or 4 school classrooms, 2 or three carriers in every movie theater, and about 685 carriers at this Sunday’s Super Bowl (68,500 seats)!

 

 


Rare Facts – what we’ve learned so far … 1 in 10 - February Rare Disease Month square

1 in 10 have a Rare Disease.
over 7,000 Rare Diseases … 30 million Americans, 30 million Europeans, 350 million world-wide are affected by Rare Disease.
80% of Rare Diseases are genetic.

rdd-logo-transparent-small
February is Rare Disease month, culminating on February 29th – a Rare Day indeed – which is Rare Disease Day.
Stay tuned for month of Rare Disease facts, tidbits and things to know.

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Over 7,000 Rare Diseases

There are over 7,000 Rare Diseases. 7000-Rare-Diseases---February-is-Rare-Disease-Month

While each of the 7,000 diseases may be rare, when you add them all up they affect 30 million Americans … 30 million Europeans … 350 million around the globe … 1 of every 10 people have a Rare Disease.

Most of the muscular dystrophies are rare … cystic fibrosis is rare … many cancers are rare .. and metachromatic leukodystrophy is very rare, affecting 1 in 40,000 births with 1 in 100 of the general public being a carrier.

rdd-logo-transparent-small
February is Rare Disease month, culminating on February 29th – a Rare Day indeed – which is Rare Disease Day.
Stay tuned for month of Rare Disease facts, tidbits and things to know.

Sign up to follow this blog and be sure to share this post.

1 in 10 Have a Rare Disease

1 person in every 10 people has a Rare Disease. 1 in 10 - February Rare Disease Month square

 

30 million Americans … 30 million Europeans … 350 million around the globe … all with Rare Disease.

Pause for a moment and think about your family and those that live around you … many cancers and most childhood diseases are Rare Diseases.  On my block of 30 homes I know of three with Rare Disease … 1 in 10!

rdd-logo-transparent-small
February is Rare Disease month, culminating on February 29th – a Rare Day indeed – which is Rare Disease Day.
Stay tuned for month of Rare Disease facts, tidbits and things to know.

Sign up to follow this blog and be sure to share this post.

 

Wanita … How a younger sister sees MLD

FB_IMG_1452703205170 My name is Tarryn and my older sister Wanita was diagnosed with MLD in 2007. She was 16 and I was 14 when she passed away and passed in 2010 from juvenile MLD. I live in South Africa.

She was so loving and so caring. Wanita was a very friendly person who loved everybody she met. It was a very difficult time for me as she was my sister. I grew up with her and I loved her. From her being there all the time to her being gone in a matter of seconds it really took a lot out of me and even 5 years later I still battle to understand it and cope with it. It was a very emotional time for my family and I but one thing I’ll always cherish is the memories we got out of it and the laughs we shared together. Right to the very end she was a happy happy little girl. Even though she was in so much pain she always managed to give us a smile and a little giggle.

I use to find it very difficult to speak about her with other people and explain my feelings toward it. I always managed to break out into tears and be very sensitive about the subject, but as time went on I almost felt like I was just staying in that bad patch and bad place of feeling alone and constantly miserable. I knew if I carried on putting it in the back of my mind that things wouldn’t get better and that I wouldn’t be able to let go. I decided to start slowly and little by little I became ok with speaking about her and listening to stories that was remembered by my family. Although I must admit I still get choked up looking at pictures but I’ve realised that it’s ok it’s not that I’m staying in the past or I’m making myself sad it’s just my way of grieving and I take a bit longer than other people do.

FB_IMG_1452703247833 I miss her everyday and I often wonder what life would be like with an older sister and think of all the things we should have done together. I never got to gossip or go shopping or go to the movies, tell secrets and all the things other sisters get to do with each other.  But I now get to make sure that my other sisters get that kind of attention from me as an older sister to them I try to fill in the missing gaps that were left behind with me when Wanita left.

I still have my difficult days and days where all I do is sleep and cry and hold her teddy. But everyday I know it’s getting better and she’s in a better place in heaven where she’s watching down on me everyday and holding my hand as I take my journey alone in this big bad world.

I miss her with my whole heart but I don’t wish her back here as I know she’s in a better place and she’s happier than she’s ever been in her life

I love you Wita  ❤

New Year’s Reflections … and Highlights from December Meeting in Boston

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Happy New Year!  As we head out of the holiday season and into a new year, it is a time that we reflect on life, cherish family, and count our blessings for all that we hold close to our hearts. Holiday music has been playing everywhere you go for the past month; while I enjoy all of the holiday songs, one song in particular, “Grown-Up Christmas List”, profoundly speaks to me at this point in my life. The lyrics are:

“No more lives torn apart,

And wars would never start,

And time would heal all hearts.

And every one would have a friend,

And right would always win,

And love would never end

This is my grown-up Christmas list.

This is my only lifelong wish”

YES. With the commercialism of Christmas in today’s society, much of this gets lost in the shuffle. But for me, and for what my family has endured as a result of the devastating effects of MLD, my grown-up Christmas list goes far beyond gifts wrapped beautifully under a tree. For me, since MLD has been in our lives, the loss we and others have experienced glaringly exposes the lies of commercialized Christmas. Shiny presents under the tree do not address our hopes and dreams. What we want is life for our children, hope for future families receiving a diagnosis of MLD. My lifelong wish is to see a cure for MLD, so that no other child has to endure what my beautiful girl, Emily, has had to endure. So that the pain caused by MLD would be avoided, and so that families receiving an MLD diagnosis would not be faced with little to no options. Emily Pierce - 2014

A few weeks ago, in mid-December, I had the privilege of attending a meeting organized by Dean & Teryn Suhr (MLD Foundation) with Dr. Alessandra Biffi and Dr. Florian Eichler at Mass General Hospital in Boston, MA. I came away from the meeting feeling like I had received a grown-up Christmas gift…two leading doctors/researchers investing and caring for OUR children and OUR rare disease. It was encouraging and refreshing. The goal of the meeting was to lay groundwork for future interaction; to discuss initiatives and action plans to make progress. [Dr. Biffi is on the MLD Foundation’s Medical and Scientific Advisory Board]

There is much to be done. Dean and Teryn are behind the scenes, pushing for good communication between those involved. Their involvement is a personal agenda that bears the weight of all of our hearts, collectively. They ultimately are fighting the MLD battle on the front lines for all of us. Dr. Eichler has been involved over the last 18 months creating a clinical & research community for ALD (adrenoleukodystrophy) called ALDConnect. The registry and community they created is a good prototype for what we can create for MLD patients to help advance research. Dr. Biffi and Dr. Eichler discussed what type of information would be helpful to obtain from MLD families. A similar patient-powered registry for MLD is in the final stages of debug by MLD Foundation (as a result of a federal grant like ALDConnect) and will be rolled out shortly. We, as the MLD Family, will become ultimately responsible in ensuring the success of information collected. A collection of information is vital for researchers to use in searching for a cure for MLD. We, as families, hold the KEY TO INFORMATION that is beyond valuable. It is my hope that we can harness our information and use it to its greatest potential.

In addition, we discussed the idea of Centers of Excellence, and what that could look like for MLD families. There is a tremendous need for knowledgeable and highly qualified centers for MLD patients and their families. Too often, our local doctors do not have the expertise or knowledge to adequately support MLD patients. With the help of a Center of Excellence, families would receive specialized care at a center, with support given to local medical teams.

Teryn’s work with developing a Newborn Screening Test for MLD was discussed. At this point a pilot study is being planned. The hope is that a 2016 pilot study will prove the test is reliable and credible. This would be HUGE!

It is very exciting to have Dr. Biffi now in the U.S. working on behalf of MLD.  It is my hope that new interest will be sparked throughout the U.S. because of her presence here. As families who have been involved with Dr. Biffi’s gene therapy work in Italy have already experienced, I was greatly impressed by Dr. Biffi’s genuine concern for MLD and desire to make a difference. We, as MLD parents, obviously want to see research done on MLD because our children have been deeply affected by it. It is refreshing to see doctors with a heart for MLD born out of their own desire to make a difference.

At one point during our meeting we discussed the burden of responsiblity that many MLD families feel in paying it forward…helping others that will come after us even if our own children may not benefit. Dr. Biffi recognized that this has affected her very deeply in her own research and experience with MLD. She personally has experienced the selfless attitude of many families to do whatever it takes for the greater good, to make the world a better place in the future for MLD, even if we may not benefit immediately from it. I was touched by her emotion and recognition of the heart of MLD families as a whole.

Ultimately, I am encouraged. Things are happening for MLD, research is being done. Not as fast as I would like, but at least it is progress. Maybe, just maybe, our hope of a cure is coming….

Centers of Excellence for Leukodystrophies and Lysosomal Disease

Earlier last month we had the opportunity to see several presentations about the Leukodystrophy Center of Excellence (CoE) at Children’s Hospital of Philadelphia (CHOP), which opened today, May 1st.
The mission of the [CHOP Leukodystrophy CoE] center is “to deliver cutting-edge, integrated, multidisciplinary clinical care, diagnostic evaluation, and therapeutics to infants, children and youth with inherited white matter disease.”
We are excited about the multi-disciplinary approach of collaborative and comprehensive care this center is now providing for leukodystrophy patients and families. Under the directorship of Dr. Amy Waldman, care plans are being developed by teams of specialists, with a designated CHOP care coordinator and extensive family/caregiver involvement. The CHOP team will include a standard suite of specialists and will include additional experts from other CHOP specialties who will come and go as situations arise. Appointments and treatments will be consolidated into one day’s visit, where possible, so families don’t have to make multiple trips to the CoE thereby improving the scope of care and reducing the burden on families and patients. We are planning to have representatives from CHOP come and present at our MLD Family Conference™ in Delaware this July.  We also hope to hear 1st hand reports from Philly area families about the CHOP CoE.
Dr. Escolar’s Program for the Study of Neurodevelopment in Rare Disorders (NDRD) at Children’s Hospital of Pittsburgh, the White Matter Disease Program under Dr. Vanderver at Children’s National in DC, Dr. Eichler’s ALD Connect program at Boston Children’s, and the Kennedy Krieger Institute Moser Center for Leukodystrophies each offer similar but independent programs, each with their own focus and roots.
MLD Foundation is an avid supporter of helping these existing centers work more closely together to improve patient care for all the leukodystrophies and to improve how network and clinical data is gathered, shared, and studied to improve care, advance understanding, and expedite therapies. This will require helping the centers to work more closely, establishing common methodologies, expanding their capabilities to serve all leukodystrophies, and putting more uniformity and structure into the clinical care and research strategies.  As resources become available the program can be expanded to include CoE’s in other parts of the country so every leukodystrophy family has a CoE close to them.
We are actively working with GLIA (Global Leukodystrophy Initiative – a two-year old international collaboration of leukodystrophy clinical and research experts), industry pharma partners, advocacy groups, and other MLD experts to develop standards of care, registries for common data collection, resource directories, access to experts, training and awareness, and maybe even provide some seed funding to help new centers to launch.  Imagine if these experts were able to implement CoE’s for leukodystrophies at all of their home medical centers – what a powerful and accessible clinical care and research force that network would be.
MLD Foundation’s OpenNHS Manifesto offers a peek into how we think pre-clinical Natural History Study collaborations should operate.  We’re thinking the CoE picture should have similar overriding and undergirding principles. Maybe an OpenCoE Manifesto is in order?

Congratulations to CHOP!

Read CHOP’s press release here

Report from FDA PFFD IEM meeting

Great Patient Focused Drug Development (PFDD) meeting at the FDA Tuesday discussing patients perspective on the neurological inborn errors of metabolism (IEM). Dean Suhr, president of the MLD Foundation, spoke on the second panel of the day and was able to both share and stir the pot a bit with regard to some of the patient perspectives on what we want in therapies, risk/benefit, access to trials in the US, compassionate/named access, patient reported outcomes, and consent.  It’s not all about statistics and biochemistry – we have life to live!

View from the panel of ½ of the audience of advocates, families, researchers, and industry

View from the panel of ½ of the audience of advocates, families, researchers, and industry at the FDA PFDD meeting on IEM.

Also met the Medical Officer at the FDA assigned to gene therapy and made sure she talked to Becky Vivian, a MLD mom who was there with her kids Eli and Ella showing the remarkable results from the Italian gene therapy clinical trial.

Both kids had the Italian Gene Therapy and are are on no post-transplant drugs.

The Vivian family – both kids had the Italian Gene Therapy and are on no post-transplant drugs. They, and the rest of the trial participants, are doing great.

In the next couple of days we’ll be sharing how to add your voice to the formal written docket for this meeting. This is our opportunity for the MLD community to be heard so we hope for many of you to share.

A MLD grandmother was also present – we had a great talk. Turns out she is a researcher and has done some work at the NIH. She wants to work with us … and you … to write a paper on bone marrow transplant outcomes. We’ll have more to share on that soon too.

Are normal enzyme levels enough to stabilize MLD?

A very interesting question came up today on the MLD Family Discussion List™ (a private list we run for MLD primary caregivers).  I thought it might inspire some thinking so I am sharing my answer here as well:

I have a question and I don’t know if anyone has an answer but I am wondering if anyone knows what truly stops this disease? Is it a normal enzyme level? Will the kids stop declining if the enzyme level stays normal? Are there other things that contribute to the stabilization of MLD?? 

Your first guess is actually correct – we really don’t know.  It will take lots of years of careful study looking at extended clinical trial/Phase III data, combined with more basic science bench work, natural history, and lots of patient & clinic reported progression/outcome data to really understand this disease.  And on top of a basic understanding we have hundreds of mutations to study.  We’re not planning on shutting down the MLD Foundation anytime soon!

From a practical perspective, the generally accepted consensus is that if the enzyme level in the blood is high enough (remember that “normal” levels vary all over the map and carriers with low blood enzyme levels appear to be metabolically “normal” people) then MLD’s progression will be dramatically slowed or halted. There is truth in this first order basic assumption – but it’s just the start of our understanding.
However (and not to scare you), there are three things to consider as we peel the MLD onion one layer (and there will be more subtleties as we further peel the MLD onion again in the future):
1) The first is that enzyme in the blood is of no value – it needs to be in the nerve cells that need it. Today’s therapies are primarily focused at crossing the CNS (central nervous system) into the brain. We measure enzyme levels in the blood and the CNS because it’s possible – brain biopsies on living people are not good! The state of our ability to get enzyme’s  large molecules reliably across the blood brain barrier (BBB) is in its infancy and the results are inconsistent at best.  The Milano gene therapy acknowledges this challenge by trying to make sure that whatever gets across the BBB produces 5-10x more enzyme than is typical hoping that the overproducing cells will share enzyme with their neighbors. Think of a gas tank in a car – a full tank shows “F” on the dial, but the engine won’t run if the fuel filter (BBB) is blocking the gas from getting to the engine (the brain).
2) The second thing to consider is once enzyme gets past the BBB will it get to all of the cells that need it?  Are some/many of those cells already compromised or unreceptive, does the enzyme (actually it’s a protein) get distributed to all regions of the brain, are the cells fixed so they keep on producing the enzyme or are they waiting for anther infusion like Enzyme Replacement Therapy (ERT) is designed to provide?  To continue the car analogy – the car may run if only 3 cylinders (brain regions) get fuel (enzyme) but you really need fuel to get to all of the cylinders (regions of the brain) to have the optimal/desired performance.
3) As mentioned, today’s therapies are primarily targeted at the brain/CNS, but our nervous system has a second component, the Peripheral Nervous System (PNS) that needs to be “fixed” as well.  The PNS makes sure the messages from the brain/CNS get to the muscles and systems elsewhere in the body.  We have historically seen a lot of transplants where the brain progression is slowed (stopped?) but the motor skills continue to decline (witness the many post-transplant children in wheelchairs).  The PNS is slightly different in its makeup than the CNS.  It also has a barrier, sometimes called the Blood Nerve Barrier (BNB), which is different from the BBB.  The common response when we ask why current research is focused on the CNS and not the PNS is that it makes sense to prioritize the CNS.  The challenge is that, to our knowledge, very little work has been done on the PNS barrier aspects of MLD. The car analogy is when the engine is running but the car is in neutral – lots of power under the hood but it is not getting to the wheels (limbs & organs) so the car is not going anywhere.
Also remember that some of these therapies require time to take hold.  The transplants need to engraft and the “good” cells take over/replace the bad cells before they can be effective. With ERT the thinking is they need to maintain somewhat consistent levels in the CNS which drives dosages and frequency of infusion.  Different issues, progressions and concerns will be at different priorities during the various early and long-term phases of each therapy.
And there are other therapies being developed as well … what if we reduced the amount of sulfatides produced so the little bit of enzyme that many MLD patients have doesn’t have to go as far?  This is called substrate reduction therapy (SRT) and hopefully will require a small molecule which, like alcohol, can more easily cross the BBB.  In the car analogy we still only get a little bit of gas through the clogged fuel filter – but what if the car was lighter and didn’t require as big an engine – their might be enough fuel getting by to be able to get from point A to point B?
We don’t have to completely understand all of this to make progress and see results in therapies.  As I mentioned above, the studies will go on for many more years and hopefully, today’s therapies will be good, tomorrows will be better, and in 5 or 10 years they will be even better as we better understand MLD, the body systems and the therapies of today and the future.  But for tomorrows therapies to be optimal, we do have to take the time to learn from every patient, every success, every valiant effort, every failure, and to explore every creative idea – many of which will lead us to increased knowledge even thought they are a practical dead-end.
At our upcoming Board meeting we are going to talk about investing in an independent formal MLD Registry to start to capture this scientific and medical history data in a more accessible scientifically managed database – we want the data to be there for future researchers to study when they have a creative idea.  And by investing, I don’t just mean a few dollars,  I mean that all of us, all of the MLD patients and their families, will be asked to contribute data as we begin to crowdsource MLD research in ways bigger than just one isolated project after another.

Rare Disease Advocacy – Behind the Scenes

I ran across this article a few minutes ago. It’s a great insight into the challenges those of us working in rare disease advocacy working encounter.

Every person and agency mentioned in this article is someone we at the MLD Foundation regularly come into contact with as we work on behalf of those with MLD.
http://cen.acs.org/content/dam/cen/91/19/09119-cover.pdf

Intracerebral Gene Therapy Phase I/II Clinical Trial for MLD

We are pleased to share that a Phase I/II Intracerebral Gene Therapy clinical trial for MLD is now recruiting late infantile MLD patients. Dr. Patrick Aubourg and Dr. Caroline Sevin are the co-Principal Investigators.

We have posted complete details of the trial, including inclusion criteria, here.

This trial is based on many years of work in the lab, and on some parallel work with ALD that showed good results.