Jeans. Genes. Thursday night, I changed from jeans into a blue dress – as in blue jean blue. The recommended color for the R.A.R.E. Gala. The focus was genes, rare genetic disorders. While most of my days are focused on Duchenne, I am very aware that Duchenne is 1 of 7,000 rare diseases.
R.A.R.E. includes more than 30 million Americans and 85% of those 30 million are children. Just outside the ballroom were photographs of people with rare diseases. Some of the names of the diseases were familiar, as I have met many families over the years: moms, dads, sisters, brothers, uncles, aunts, friends who love a person with a rare disease. They all remember the exact date and time when this new word, this diagnosis, broke down the door of their home, and interrupted the life they were planning to live.
There was a little girl, about 2, SMA type 1, immobile and in a vent. Another little girl of about 7, mobile, but unable to communicate, Phelan-McDermid Syndrome, suggested to be the genetic cause of autism. A boy with Fragile X Syndrome. And so many more.
The photographs and the people told the story of unmet needs, of parents and families feeling isolated and alone, and of HOPE – the belief in biomedical research, scientific opportunity, and treatment. And also, the HOPE of connection.
I stood staring at the pictures, watching the families, in tears. The mantra in my head... Children should not be sick. They should have opportunities and dreams. And every child I met was smiling, happy, deeply loved. It was quite an evening.
I accepted an award for advocacy, but the award does not belong to me. It belongs to all of us and especially to our children. They smile in the face of a diagnosis that brings us to our knees. They teach us about hope, about living each day, about appreciating the gifts we have. They teach us the real definition of strength.
I walked up to the podium, humbled by the evening… I started off saying:
I am very grateful and honored to be part of this amazing celebration. It is an honor to be in the presence of my personal hero’s such as Dr. Emil Kakkis, Brad Margus, and John Crowley and so many of you sitting in this audience.
Duchenne muscular dystrophy is a RARE disease. Perhaps medium rare…
Approximately 250,000 individuals in the world are diagnosed as having Duchenne muscular dystrophy.
Approximately 12,000 of those individuals live in the United States.
To be honest, Duchenne affects millions of people – the diagnosis of Duchenne or any RARE disease refers to an individual, but the impact of that diagnosis ripples through families, neighborhoods, schools, and communities. Everyone in the world is touched by a RARE disease.
Duchenne muscular dystrophy is x-linked, which means that Duchenne primarily affects boys and young men. Women can be carriers (I am one of them) and some of them are symptomatic.
My sons Christopher and Patrick were diagnosed with Duchenne in 1984. They died on September 29 and April 29, in 1995 and 1996, 7 months apart-to the day and to the hour.
The ‘Duchenne gene’ is the largest gene in the human genome, with 79 exons and 2.5 million base pairs. Mutations occur across the gene and result in the loss of a structural protein called dystrophin. Dystrophin plays a critical role in muscle. It acts as a shock absorber, an organizer, and a regulator. Without this protein, muscle cells are unable to survive.
As babies, most parents would never recognize signs or symptoms of Duchenne as they are subtle. These wonderful boys gain skills such as sitting upright and walking as anticipated, though sometimes there are slight delays. Most of the time, if mom or dad expresses concern, the delays are dismissed by pediatricians and family doctors.
Once diagnosed (and even before) the clock starts. Over the next 20 years, they will lose the skills they worked so hard to gain. At 16, when their peers think about driving, young men with Duchenne are typically unable to walk even a step. Soon after, they will be unable to throw their arms around someone they love. By their 20s, most of the everyday things we take for granted (feeding, personal needs, scratching our nose) will take extraordinary effort or become impossible. Keep in mind, the heart is a muscle too and by the age of 30, it will fail.
Because all of us are RARE, we face the same challenges.
Finding our gene. Understanding the pathophysiology of the condition – what is missing because of the genetic mutation? Identifying targets for potential intervention and repurposing drugs or developing new drugs. We have to think about addressing clinical variability and standardizing care. Understanding progression and collecting natural history studies with sufficient rigor for FDA. Developing clinical trials in small populations and thinking ‘out of the box’ about adaptive designs to include patients across the spectrum of the condition (in Duchenne – ambulatory and non). And progress may be slowed and difficult because of absence of biomarkers and validated outcome measures, the recognition that success or failure of clinical trials depends on primary outcomes or surrogate measures, and data statistically relevant for approval.
We need and advocate for regulatory authority – for the FDA to understand that RARE is complicated and flexibility will be required- that it is may sometimes be difficult to ‘tease’ out benefit in the context of a clinical trial and that vehicles such as conditional approval (Europe) and accelerated approval (US) need to be in embraced and post marketing studies required if we are to understand benefit from a given compound. This year, in particular, we, the RARE disease community, worked on this legislatively with PDUFA5 and FDASIA.
And for all of us to discuss benefit /risk in the context of rare disease – what is the risk tolerance and where do we set the ‘bar’ for benefit. I would have been grateful for 5 additional minutes with my sons.
And approvals, TREATMENTS: the holy grail and the recognition that our work is not complete until we are able to ensure ACCESS for all who may benefit from a given therapeutic intervention.
I cannot imagine how it would feel to know about a therapy, something that might change the predicted outcome for someone you love and to be denied access – for whatever reason.
This is why we are here. This is why we need each other and depend upon each other. WE are RARE and together, we are louder, stronger, more visible, more effective.
I’m often reminded of the story Horton Hears a Who. Horton, the elephant knows that size doesn't matter – whether you're as big as an Horton or as small as a speck, RARE is all of us. We ARE the people of Whoville and we may be tiny but if you will remember the story of WHOVILLE:
Their voices were heard. They rang out loud and clean.
And the elephant smiled, “Do you see what I mean?”
They proved they ARE persons, no matter how small (rare).
And THE whole world will be saved by the smallest of all.
My deepest thanks for this wonderful award.
A person’s a person, no matter how small…or how RARE. Thank you. God bless and Godspeed to all of us.
And as I walked off that podium, I whispered a prayer to Chris and Patrick, thanking them again and again for the journey.
Pat Furlong, Founding President, CEO
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