My talk at NORD

Last Monday, I got the chance to tell people about my journey with gene therapy. Those who know the story might recall it dates back to Cal's diagnosis back in 2012. Preliminary success in a clinical trial for MLD would come too late to help Cal. This breakthrough had, at first, filled me with despair because we had missed our chance to help Cal by just a year or two.

But. it was Cal's neurologist, Dr. Amy Waldman, who made the remarkable suggestion to help children eligible for the trial get to Italy. I like to tell my friends that courageous mom persona is a little more than act. But, since the alternative was despair and doing nothing, selling the cupcakes seems like the easy decision with the passage of time. But, it was not easy back in 2013 when Pat and I were trying to figure out what we do.

So many people had assumed it would be difficult to talk about Cal and how our pain over Callie could coexist side-by-side with our hope for other people's children. But, for me, the only way I have found to tame grief is to turn it into a story.

So, I was rather nervous- and amazed- to speak at the National Organization of Rare Diseases (NORD) meetings in Washington DC. I had figured a few dozen people might attend the panel, and then to see see the standing room only crowd, took my breath away. A friend later told me they had had to close the doors to turn people away because the room had become too crowded.

I am glad I eschewed my customary informal, off-the-cuff style to use a script. I could not take the chance that I would cry or lose my train of thought. I wanted to be clear so as not squander my 10 minutes in front of people from patient advocacy groups, biotechs, and the FDA.

The speech was a remarkable experience, I got a standing ovation. In the movies, people get ovations all the time. In real, they are rare. I have been giving talks for 20 years as an academic and I have never received a standing ovation. I doubt I will ever get one again.

So many people came up to speak to me afterwards and thank me. But one man stood out. The man was in his early 60s, I would guess, he explained he was a pediatric neurologist and that he had lost his brother to Tay-Sachs disease as a child in the 1960s. With tears in his eyes, he said, "Thank you so much for sharing this story of gene therapy, it is amazing, I just wish my mother had lived long enough to see it." Here was a grown man, a doctor, still so overcome by the loss of a child more than half a century ago. And, after hearing me talk about gene therapy, he longed to tell his own mother about this miracle.

And as I studied the man's face, I was reminded - once again- how grateful I am to have witnessed these breakthroughs in Cal's lifetime, and mine. So, a couple of you have requested the text of the speech. I wrote the orginal version of the speech in about 30 minutes, but, the truth is I have longing to say these words for so many years.

Below is the original text of the talk.

Every single day, I wake up thinking about how to get gene replacement therapy to the children who will benefit from these breakthroughs.

I am not a doctor or a researcher or even an employee of a biotech, I am just a mom who through a set of remarkable circumstances got a front row seat to one of the biggest medical breakthroughs in a generation.

Before I speak today, let me start by acknowledging Dr. Kathy High and the researchers at Spark Therapeutics who made history last Friday with an unanimous vote of support for the first gene replacement therapy to treat an inherited disorder.

I would not be here speaking to you without the work they have championed over two decades.

My advocacy for gene therapy dates back to July 5th 2012, when a neurologist at the world-renowned Children’s Hospital of Philadelphia explained that our youngest child, Calliope, Cal, had late infantile-onset metachromatic leukodystrophy.

MLD is one of the 50 diseases in the same family as Tay-Sachs and the Lorenzo’s Oil disease (also known as adrenoleukodystrophy). My daughter Cal was not expected to survive beyond the age of 6. We are grateful that Cal will celebrate her 8th birthday on December 23rd.

On the year anniversary of Cal’s diagnosis back in July 2013, I read an article in the journal Science. A researcher named Alessandra Biffi at the Telethon Institute in Milan, Italy had successfully treated 3 children with MLD using a gene replacement therapy.

The team had hoped to give the children a milder form of the disease, instead, much to the amazement of Dr. Biffi and her colleagues, some of the children were not developing the disease at all.

To cope with Cal’s diagnosis, my husband Pat and I had started hosting bake sales and selling cupcakes to raise funds for a foundation we had started in honor of Cal.

It was around this time Cal’s neurologist, Dr. Amy Waldman, made an amazing suggestion that would change all of our lives: She asked us to take the money we raised from selling cupcakes to help families get to Milan for the trial.

It was an astounding idea. I told Dr. Waldman, "you have mistaken me for a brave woman." And then Dr. Waldman reminded me how every family in the trial had sacrificed one child for the chance to save another. "So, of course you will help them."

And so, since 2013, the Calliope Joy Foundation has sold 30,000 cupcakes, helped establish the nation’s first Leukodystrophy Center of Excellence at the Children’s Hospital of Philadelphia and sent 10 children to Italy : five from the US, two from the UK, one from Australia, one from Ireland, and one from Switzerland.

These children became our investments in a miracle.

Lately, gene therapy has been in the news, but, this research has been around since 1990 when 4 year old Ashanti DeSilva, became the first patient in the world treated with gene replacement therapy ADA-SCID (or Bubble Boy disease). Ashanti is now 30 years old, but after this initial success gene faltered after a death in a clinical trial and several cases of patients developing leukemia.

Funding dried up and trials were shuttered.

Gene therapy had proven more difficult than researchers imagined. Geneticists have been able to alter the genes of plants and animals for generations.

The challenge for gene replacement therapy was figuring out how to transport the repaired gene into a patient’s body.

And, as it happens, nature offered a vehicle: viruses. Viruses are really good at getting inside our cells and telling them what to do, so gene replacement therapy uses viruses stripped of their dangerous parts - also known as vectors- to infect patients with the working copy of the broken gene that causes some 6000 inherited disorders resulting from a single, faulty gene.

Constructing vectors that are safe, fast-acting and efficient had proven a far more elusive.

Dr. Biffi and her colleagues had come up with an ingenious if somewhat unsettling solution: HIV.

Biff and her colleagues understood that AIDS had been so very lethal because HIV was so good at getting inside our cells and telling them what to do. .

You had to admire the courage (touched with insanity) of using the virus behind the worst pandemic in a generation to save children’s lives and defeat a disease like MLD.

It’s been 27 years since Ashanti De Silva was treated and we are still coming up with a language to describe this new sort of medicine.

Gene therapy might be a miracle but it is not a cure.

The best way to describe gene therapy is that it slams the brakes on disease to prevent children from getting sick. Gene replacement therapy for MLD and other neurological disorders has to be done before the children start showing symptoms since the treatment cannot undo the damage to the brain and central nervous system. Newborn screening will be crucial for this new frontier of medicine, and lots of people in this room know how difficult that will be.

In the best case scenarios, children with MLD remain stable and asymptomatic for years, and we hope, over a very long life. Other children show more signs of the disease and may use walkers and wheelchairs. But even in these cases, the patients are spared the disease’s most devastating symptoms such as needing a feeding tube or respiratory support.

So let me conclude with what I tell families we send to Italy.

Gene therapy is a miracle, but, what most people do not understand about miracles is that they don’t just happen because we wish and pray for them or even because we deserve them.

Miracles must be earned through hard work, sacrifice and even suffering.

And I am so blessed because I have met children who should be paralyzed, feeding tube dependent, and near death who can run and play. I have watched them celebrate birthdays and sing songs and dance and ride bicycles and throw footballs. It has been the greatest honor of my life to witness this incredible breakthrough for my daughter’s disease in my lifetime and her lifetime.

None of this will make up for losing Cal, but it has given us a way to keep going, it has given us hope.

And I am here to tell you I can’t wait to see what happens next.