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

openNHS Manifesto – Meeting Report

A meeting of researchers, clinicians, industry and academia was convened by the MLD Foundation on June 24th in Washington, DC to discuss the openNHS Manifesto we wrote about in this blog post.

Since a NHS is not a therapy, NHS participants have historically be giving time, energy, and effort, not to mention exposing their MLD loved ones to occasional invasive and potentially painful testing with limited feedback from the NHS study teams.

The openNHS Manifesto

  • recognizes the importance of NHS to better understand the disease and as a baseline to determine efficacy and obtain regulatory approval of new therapies.
  • calls for the NHS study team to be well-informed about MLD and to give back to the participants ideas and insight into improving the participants quality of life and ongoing clinical care.
  • calls for study sponsors to collaborate pre-clinically up front with other researchers and industry to design a study that meets the sponsor’s needs as well as  reasonably anticipated future needs
  • calls for study data to be open and accessible as raw data (in its entirety) to future researchers.  The Manifesto recognizes that some limited time protection may be necessary to honor publishing and IP rights.

At the DC meeting there was extensive discussion and sharing of perspectives and concerns about openNHS from many points of view.

We are pleased to report the meeting was a success on all fronts!  MLD Foundation, on behalf of those affected with MLD and the ongoing research community, was able to facilitate full support of the Manifesto and will be working with MLD collaborators in general, as well as Shire as sponsor of the current US late infantile NHS, to implement the Manifesto on current and future MLD Natural History Studies.

We look forward to sharing more specifics about what this means to MLD families and NHS study participants in the near future.

We will also be sharing our success with other advocacy groups with the hope that they too can call for openNHS in their communities.

Join our call for OPEN Natural History Studies

A new Natural History Study (NHS) for MLD was launched a few weeks ago. We have taken the bold step of recommending that families NOT participate in this study … for now:

It is our belief that all natural history studies be OPEN access, meaning the study data be maximized by being made available to other researchers from other academic institutions and companies, and be as collaborative as possible. Properly designed studies will protect your privacy while maximizing the use of your data to facilitate longevity in MLD research. 
In our opinion this new NHS does not adequately meet this criteria. We are (February 2014) in discussions with the study sponsors to address these concerns.
from http://mldfoundation.org/research-natural-history.html (see the detailed explanation near the bottom of this page)
This study is the fourth NHS that we are aware of for MLD and was launched by a long-standing pharmaceutical partner and MLD collaborator, Shire. We want to be clear that our don’t participate for now recommendation is not a Shire specific issue nor is Shire resisting discussing our concerns. Further, this “not participate”  stance is not because there are any fundamental scientific problems with the study, rather it’s that we want to optimize the value, usefulness, and knowledge gained from this rare disease Natural History Study for the researchers and for the patients.
We are actively working to bring the MLD community of Shire, GSK, Biomarin, several academic institutions, several other advocacy groups, and even some local treating clinicians together in the next month or two to collaboratively work on the following concerns and requests so we can get back to helping recruit for this study.
We are asking for two things before we encourage families to participate in this, or any other Natural History Study …
  1. OPEN collaborative Natural History Studies … meaning that the study is designed collaboratively and all ofthe the collected RAW data is made available openly to all future researchers.
    • MLD natural history studies are invasive and painful for the child who participates (nerve conduction and Lumbar Puncture/Spinal Taps). They also require a commitment that significant time and energy be put forth by families to make the repeat their visits to the study center knowing that they will not be receiving any therapy clinical trial access, i.e. they are giving to hopefully help the next generation of patients, not their own children.
    • Today, the current practice is one company designs their own NHS, collects and silos the raw data, uses the data for their application with the FDA, and then publishes the highlights.  Since only the summary data is published, the next company has to start from scratch with their own new study, engaging & testing more patients, etc.  That requires twice as many patients, twice as much patient sacrifice, twice as much cost, and perhaps twice as much time.  We don’t have a large enough community or enough time to double and triple dip – in fact, yesterday we lost another MLD patient, the 9th we know of this year.
    • The results from natural history studies are necessary for a new FDA/EMA therapy approval applications,however, these patients are untreated so their data is independent of any particular therapy.  Hence a NHS, just like developing a newborn screen, is a matter of common concern, not competitive advantage.
    • We are asking that Natural History Studies be collaboratively designed, collaboratively implemented, and all RAW data (not just the published summaries) be available for any researcher to access for any future study.  This collaborative approach will likely involve cost sharing as well so it’s complicated to set up but this approach allows us to gather the data as efficiently and as quickly as possible – while optimizing the “use” of the patient community.
  2. Give back to the patients/families with each NHS study visit … give the families information to take home after each visit to help them improve quality of life for their loved ones.
    • The NHS study centers have experts in gathering the NHS data, however, while they may understand lysosomal disease or leukodystrophies in general, they are generally not currently providing any direct MLD clinical feedback to the patients.
    • We already have a model for this in our community, the NDRD in Pittsburgh. In fact, families visit and re-visit the NDRD from literally across the country for the clinical expertise  and are then recruited into the natural history studies.  The NDRD has become a source of expertise and clinical support for many similar rare diseases.  They give clinical recommendations to the family to improve day to day quality of life and also become a medical resource for the local treating care team in the family’s home town.
    • We are asking that each study center be equipped to be a Center of Excellence for MLD where they can, and do, provide clinical expertise with each visit in addition to gathering the specific NHS data. This approach, as has been demonstrated by the NDRD, is a model that works for research and the families.
    • We are working to develop a Standard of Care for MLD to further support these clinical Center of Excellence goals and the local treating physicians when they go back home.
To our knowledge, no patients have been recruited for this specific Natural History Study.  We hope to impact the collaborative and clinical nature of how the study proceeds before any patients are enrolled, and frankly do not think these requests will impact the core study design in any significant ways.  As we all know, once patients are enrolled and data gathering momentum is established, change becomes more difficult.
We have excellent contact and influence with the MLD families worldwide. We are using this position and those relationships to try to affect a fundamental change in how Natural History Studies are implemented for MLD and for all rare diseases.
It is very bold to take this sort of position publicly – but it’s our moral responsibility to stand up for the patients.  We firmly believe this “patient-first” while “optimizing research” stance is optimal for patients and researchers.
If your organization supports this philosophy for OPEN Natural History Studies please comment here and then email us to let us know.  Advocacy groups can be the catalyst for these changes.
Dean Suhr, President  co-founder
MLD Foundation  http://MLDfoundation.org     
We C.A.R.E.™ for MLD families around the globe … for over 13 years!