We have 20/20 Vision for MLD

2020 will bring new clinical and therapeutic care to the MLD community.

When we started serving MLD Families in 1999 – two decades ago – we had no idea how challenging and time-consuming it would be to improve clinical care and disease altering therapies.

Along with your support, we’ve done a lot of heavy and consistent lifting these last 20 years.

If you read nothing else of this blog, please know that we gratefully THANK YOU and wish you and the MLD community a Happy New Year!!

Our Time is Now!

We look forward to reaping the benefits of these past two decades and our ongoing work during 2020 and the first couple of years in this new decade. During 2020, after many years of research, pilot studies, and clinical trials, families will start to benefit directly as this work becomes available to families to improve the quality of life for those with MLD.

NEWBORN SCREENING … Newborn screening is critical to identifying MLD at the earliest possible time – birth. These infants will have the greatest benefit from current and new disease-altering therapies.

We’ll see the launch of newborn screening in the first US public health system in parts of the state of New York as a precursor to a federal RUSP application, screening in more US states, and adding newborn screening to various international health systems too!

Teryn Suhr of MLD Foundation took the lead to develop the screening technique that is being used today. We’ve led in instituting powerful state NBS policy in California and Florida. We’ve hosted a Newborn Screening Summit for MLD experts and will host several more this year. We are continuing and expanding work as we are coordinate and manage a federal RUSP nomination as well as state-by-state & country-by-country MLD newborn screening implementation.

Early diagnosis through newborn screening and an expanding choice of therapies means each family can choose what is best for their child.

GENE THERAPY … gene therapy clinical trials have shown extraordinary results with pre-symptomatic children. Orchard Therapeutics filed with the EMA this past fall and should have their response – hopefully, an approval – around mid-year. We hope the US FDA review will start in early 2021 – maybe sooner!

Homology Medicines is seeing excellent pre-clinical research for its novel approach to gene therapy.

MLD Foundation is and has been working with at least four other pharmaceutical companies and research spinouts but cannot share more about their pre-clinical work (yet) due to NDA requirements. We speak regularly with startup companies and venture capital companies about the opportunities and challenges surrounding MLD.

And there is more …

STEM CELL TRANSPLANT … we are seeing ongoing improvements in MLD stem cell transplant, MLD’s only widely available therapy. In addition to the studies underway at various hospitals and academic institutions to reduce mortality, reduce chemotherapy, and improve outcomes for current MLD transplants, Magenta Therapeutics has a clinical trial studying cell-expansion and is working in the lab to eliminate chemotherapy as part of the transplant process.

BETTER DISEASE UNDERSTANDING … There are over 300 mutations known to cause MLD – that’s 90,000 potential mutation combinations. We only know the progression of a handful of those mutation pairs with decent certainty. MLD Foundation is actively engaged in a genotype-phenotype study to better help families make optimal informed quality of life clinical and therapeutic decisions.

We’re also active in two academic Natural History studies and operate an MLD Patient Powered Registry where MLD families are sharing their MLD journies so we can improve not only the medical care, but also improve the social, emotional, financial, public services, and creative family-driven/inspired quality of life strategies and decisions.

We have been meeting with the FDA since 2007 to expand their understanding of MLD and the therapeutical needs of the community. As we get closer to a regulatory filing we will both focus and expand the communications with the agency.

But not everything about living with MLD is medical

COMPASSION AND SUPPORT FOR FAMILIES … We do our best to address the needs of MLD families in hands-on practical ways … some recent examples of direct engagement: we’ve helped several families get wheelchair vans for their loved ones, We’ve re-purposed medical equipment, provided logistical and financial support to help a family get same-day passports to get to Italy for gene therapy evaluation, helped overturn MEDICAID out of state therapy rejections, visited Italy to help a family enroll in the gene therapy, helped families make numerous therapy and non-therapy decisions, appeared at a deposition to help a family get in-state MEDICAID support for their family.

But perhaps the most impactful work we do is when we meet with families in person, at conferences, and over the phone. As we all know, an MLD diagnosis is just the start of a journey filled with decisions impacting all facets of life all while grieving the impact of MLD on a loved one and our parental/spousal expectations for life.

We spend hours on the phone with many of the newly diagnosed families helping them to learn about the disease, what to expect, clinical and therapeutic decisions, life decisions, and just being there with them as they digest an overwhelming amount of information and make decisions no parent or spouse should ever have to make.

And of course, we have host an annual MLD Family Conference™. This is where you can meet with dozens of other MLD families face to face with extended time for conversation. There are always MLD clinical and research experts to engage as well. In 2019 we launched the MLD Newborn Screening Academy. In 2020 we will continue that education and empowerment. MLD cannot reach the finish line without your direct efforts in your home state.

How Do We Do It?

We do all of this with your support … financial, time, energies, introductions to your connections and resources, “tips” about new ideas, approaches, and activities, and with the support of your thoughts and prayers.

Our philosophy has always been to try to meet researchers, companies, regulators, policy-makers, investors, other advocacy organizations, and most importantly, families, in person whenever possible. We visit them in their offices, labs, hospital rooms, and homes. We have found that we can have more intimate, detailed and informative conversations in person than via email or phone. We make it a point to share whatever information we can to connect the knowledge, needs, and experiences of one person with another … and sometimes that includes finances too! We’ve seen dramatic results and huge leverage with this strategy.

As you can see below, it’s a lot of nights on the road on your behalf. Life with MLD never stops so there are no days off … we are always honored to be working for you as our mobile phones and laptops travel with us.

The total is since 2008, when we started using TripIt to manage our travel.

In addition to face-to-face meetings, we spend extensive time in Washington DC with the FDA, NIH, other advocacy groups, and policy-makers. There are a half dozen or so key conferences and events each year. However, we don’t just attend those conferences, we also actively participate by presenting, booth displays to educate, posters to educate, and participating in panels to inspire.

MLD PATIENT POWERED REGISTRY … This is how our experiences are being gathered to impact researchers, clinicians regulators like the FDA, and policymakers. Unlike most natural history studies that only ask a small number of families a limited and focused set of disease-specific medical questions, the MLD PPR covers all aspects of life with MLD … from diagnosis to extended family, finances, clinical care, social services, and much much more.

As we gather more data we gain breadth, understanding, and perspective. All of this allows us to have a greater impact as we use the data. Researchers can request access to the de-identified data so they can efficiently advance their work.

We want all families to participate … no matter how recent or long ago your MLD experience is, no matter if your loved one is living or has passed, no matter what your home country is – everyone has MLD journey experiences to share and for us to learn from.

How Can You Help?

Reach back to us and let us know you are interested. Every one of you has skills that enhance or expand what we can do, knows people we don’t, and lives in a different part of the country or the globe.

Got a minute? 2 minutes? 60 minutes? We will be blessed by just a minute or two whenever you can spare them.

We recognize that your emotional and physical needs will ebb and flow as you navigate the MLD journey. We know that too, so we will always try to make sure you are supported and not overwhelmed.

Do you love social media? We have a special need for someone or multiple people to help us with our social media.

— 
Dean Suhr
President
MLD Foundation
21345 Miles Drive
West Linn, OR 97068-2878 USA

1+503-656-4808 or 1-800-617-8387

http://MLDfoundation.org Serving the MLD Community since 2001We C.A.R.E.™ … We are the largest charity worldwide focused on MLD family Compassion, Awareness, Research and Education.

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….

Mld Family Conference™ – Register Now!

MLD Family Conference™ - Pittsburgh 2014 - low

MLD Family Conference™ – 2014 Pittsburgh … click to enlarge

Registration for our 2105 MLD Family Conference in Newark Delaware is underway and closes in just a couple of weeks.  If you are a MLD Family we’re anxious to have you register.

Many of your MLD Family will be there to meet, share, and socialize with.
Please bring your MLD loved one with you – we not only want to meet them, we have a special professional photographer to take your family’s photo while capturing the spirit of our special loved ones and the MLD journey through photography.
You will again find familiar faces in the Respite room to care for your other children and your MLD loved ones.
Those with MLD angels are always lovingly encouraged to attend – you have so much to share with the rest of us and you will surely find folks that “just get it”.
Conference details and an agenda are here: http://mldfoundation.org/mldfc/mld2015-de.php  We’ve organized some travel grants as well as registration scholarships if you need some help.
Some other highlights:
* Dr. Biffi will be attending (in person) and sharing/discussing the Milano gene therapy clinical trial.
 
* Shire will be discussing their ERT clinical trial status and sharing some interim results.
 
* Newborn screening … updates on the assay development, federal/state policy & actions, and the RUSP Roundtable we are organizing … and how you can help!
On Saturday, as usual, you will drive the Practical Care agenda, … including a discussion about medical marijuana  & CBD oil .
* We’re working hard on a special fun Saturday evening event, a memorial butterfly release, the traditional MLD “bashing”, and MLD After Hours.
We have many of the global MLD experts attending so you can meet them and ask any questions you may have.
With travel support and scholarships available, all you need to do is register!  You can defer paying the modest registration fees for a few weeks if you need to, but we want to know you are coming so we save the right number of sleeping rooms!

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

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.