On any given day, all of us can site ‘things coming together’ to achieve a certain goal.
- Landing on the moon
- NASA International Space Station
- Trapped miners in Chile
- Air Traffic Control around the world
- UN (ok we could have a long discussion about efficiency, effectiveness, and benefit but nevertheless, an extensive collaboration)
- Identifying the Dystrophin Gene
- MD-CARE Act 2001
- MD-CARE Act Reauthorization
- Care Considerations
The list of achievements when people come together is immense and stretches (I’m guessing) from the Earth to Mars and back several times. And in the case of examples such as the moon landing and the miners in Chile, these are actually engineering problems, certainly with variables, but to some degree predictable with complex algorithms, brilliant engineers, and Star Wars technology. Chilean miners survived because they were able to engineer a lifeline and once stabilized, had some time to figure out the rest.
In Duchenne, there are any number of variables and few algorithms to predict the intricacies of the Duchenne gene, the complex interaction in all human cells, and the impact of other factors – psyche, spirituality, environment, chance. First, there are many foundations, organizations, individuals, companies, governments concerned about Duchenne and about rare disease. We should all be thrilled and grateful. Some have a specific focus in terms of basic science (understanding the biology of Duchenne, which is incredibly complex and unknown); to understanding what optimal care looks like, what interventions would help, at what age and under what circumstances; to drug development (which depends on understanding the biology); to biomarkers (what proof will we have that something works and how will we know); to outcome measures (how to understand improvement in a progressive/degenerative condition); to treatments (what works, what does not, how will we know); to alternative therapies (click here
to read PPMD's recent statement regarding alternative therapies); to individual variation in disease course; and the list goes on and on.
So, if we all came together and focused on one area, what would it be? The answer may depend on a certain child, a certain concern, a certain belief in an emerging therapy, a certain philosophical view (newborn screening, stem cells: adult-derived or embryonic, etc.) or some other idea. And for some individuals or foundations, things change and what they do may change as the disease changes and priorities /needs change.
For me, the good news is that the investment in Duchenne has dramatically increased, that biotech and big pharma is onboard, that the US government (and other governments are interested – a sort of UN for Duchenne is forming), that some of us focus broadly (basic science, drug development, improving care/treatment, biomarkers, outcomes, regulatory, insuring access, advocacy), while others are focused on a certain niche. BUT–and this is what is so wonderful about this community– when we see a place where collaboration would be useful /helpful to move collectively, we do. Examples include support for meetings, conferences, clinical studies, workshops, biotech, industry, advocacy, and so much more.
It is easy to imagine that if we all come together we would have a cure sooner. This is not certain because of the many complexities of Duchenne across the spectrum of the disease. But, if all of us do something, the collective effect is BIG. Today, rough guesstimates of investment in Duchenne are in the billions of dollars. Pretty impressive!
I wish Duchenne was an engineering problem but it is a human problem, characterized by the amazing capability of cells, interacting with billions and billions of other cells, sending messages and triggering effects. Think of the impact of steroids… and we are just capturing natural history with steroids to learn the impact, how the disease has changed. Before steroids, boys went off their feet at 8 +/- years of age. With steroids, some continue to walk in their teens. Steroids has expanded the variability of Duchenne. We still do not understand exactly how they work. We all agree, steroids impact the immune response. Some think steroids stabilize the muscle membrane. Some think steroids upregulate utrophin. Maybe it is all that and more with obvious and significant variability. There are some boys who do not respond to steroids. Why the variability? Does it depend on something in the immune response? Is it related to genetic mutation? And what do we know about certain mutations other than the in-frame/out-of-frame rule that works, except when it doesn’t? What do we know or need to learn about the various parts of the dystrophin gene, for example the ‘hinge’ region? And think of the recent paper from Jerry Mendell, suggesting that some boys have an immune response to dystrophin and some do not. We need to learn a great deal more about this as we test Ataluren, AON, and gene therapy approaches. And what of the paper from Salvatore
, talking about mutations in the area of 45-55 and what we are learning or may learn about ‘in-frame’ and the potential benefit/risk of skipping certain exons? Think of the recent sudden deaths – the fall, fracture and following loss of one of our beautiful young men. We think the heart developed an sudden abnormal rhythm and failed. How will we learn what happened, what rhythm? Who is at risk? How will we know? What do we need to do? And what if the therapies are expensive? Will insurance cover? How will boys on Medicaid, especially in struggling states access? How will boys all over the world who have limited or no access to sequencing (diagnostics) or care and potentially never to therapies – how will we help? And consider if we need large numbers for clinical trials in a precise cohort (age x-y, walking…) how will we find sufficient numbers to participate in all of these trials (required to power a given trial and essential to prove benefit) in order to get to approved treatments?
These questions are not to overwhelm. They are just to point out the enormity of questions left to answer in this disease. Which is why collaboration is essential. All of our individual voices turning to the gifts and talents of this community and then answering the big questions as ONE VOICE.
In looking at what needs to be done, recognizing the enormity and scope of our ‘moon landing’, it feels good that we are all able to connect, able to applaud differences, and can be thankful for investments across a broad range of relevant and important projects. It feels good that we are a community – with all of our faults, with all of our own human experiences and baggage to contend with, all of us doing something to help.
And in a similar approach to the Chilean miner rescue, we have
established the lifeline and are working to improve it (diagnostics,
care), while we figure out the rest (biology, drug development, access).
There is no foundation, organization, academic institution, biotech, pharma or any individual that is doing something better or of more value. It is all pieces of the pie, building blocks to treatment. No one organization, person, company has the ‘ticket’ to the cure or the ‘ticket’ to get in trials. This is a big job and there is a place for everyone who is willing to help. Duchenne is hard, complex, fascinating, and heartbreaking. But this community is unstoppable. We are