Capitol Hill, BIO, 21st Century Cures, Airbnb, and one more thing … Reflecting on my DC week

The first rule of blogging is to post good content on a regular basis.  The second is to keep your posts short, to the point and to not mix multiple topics into one post.  Oh boy, am I in trouble …
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My 6th trip to DC this year ended reflecting at 35,000′ with a Crater Lake Hazelnut Espresso Vodka courtesy of gold status on Alaska Airlines as I flew non-stop back home to Portland Friday evening.

I cratelakevodka admit I was stoked because of so many good people, connections, meetings, and events that I had experienced over the past three days.

And then I connected to Alaska’s WiFi …

Before I tell you what I learned from the world below,  let me share a few of the other highlights … each of which I will share much more about in coming posts.

13 Senate ofice meetings in one day

Jay Griessing of Biomarin set up and attended 14 Senate us-senate office meetings and one House meeting with me … 13 Senate meetings on Wednesday alone!  I have been to Senate offices many times over perhaps a decade – my prior max was 6 or 7 meetings. And better yet, because Congress is in recess (out campaigning) the two of us were very efficient as we meet with the staffers who do the real work on the Hill.

21st Century Cures is alive

curesnowpict We discussed 21st Century Cures, its history and what we hope to accomplish over the next few weeks during the lame duck Congressional session.  The short update … there is a lot of enthusiasm on both the Senate and House side to get #CURESnow passed.  It might be slimmed down a bit but we’ll take it.

Rare Policy

rarepolicy-home-pages-draft A missing voice was identified at 21st Century Cures strategic planning meeting held two weeks ago duringmy 5th trip to DC at the NORD Rare Disease Summit.
We need the voice of the patients, families, caregivers, and general public to push CURES to the finish line.  I am about 24 hours away from launching a platform that lets this audience contact Congress with 1-click in a much more impactful way … and gives those of us managing these programs a lot more ability to build on these grass-roots networks.  I spent three late nights last week communicating with a development team in India … and watching the Cubs historic win streamed to a small corner of my screen.


BIO Patient & Health Advocacy Summit

biosummit2016 I again attended this annual gathering of advocacy and industry. The #BIOsummit2016 sessions and particularly the networking was exceptionally rich this year.  BIO does great job of balancing the content and attendance so we all come away enriched and informed.  I spent time with dozens of people from multiple stakeholder communities … advocacy, industry, policy, organizational leadership, consultants, communications, etc.

Airbnb

airbnd-chic-14th-u airbnb-new-logo-1-1024x863 Ok , I’m adventuresome, frugal with MLD Foundation funds, and we’d reached our quota of room nights with Hilton family hotels to keep our status with them … so I made my first Airbnb reservation and stayed at a place described as Chic designer-rustic, 14th & U Neighborhood, Metro (if you sty there tell them Dean recommend you).  A 3rd floor room, a tiny European style bathroom with a sideways sink, WiFi and great hosts.  I’m no longer an Airbnb virgin.

And then

edengetsherwings201611 One email subject line whisked me from this whirlwind activity, progress, and networking and reminded me of the reality of why I’m doing this … Eden gets her wings”.  Beth is not a MLD carrier and Eden was healthy by all accounts when she was adopted from Ethiopia by her single mother, Beth.  7-year old Eden was finally free from MLD, but no longer with us.  Late infantile MLD starts to show its devastation around 18-24 months, just after Eden was brought to the US to live what was supposed to be a happy healthy life.


#FMLD fmldcar … which properly stands for Fighting MLD … but that’s not quite how I feel right now.  ;(

I love what I do … and yet I hate the reasons I ever had to start doing it.  MLD and Rare Disease are my passion and focus … but there are times where overall health and sometimes even bigger things are the concerns.

more to come …

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.

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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.

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.