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Founder Maria Kefalas addresses NORD Summit

This is the text of a speech Calliope Joy Foundation founder Maria Kefalas gave at the National Organization of Rare Diseases (NORD) Summit in Washington, DC on Monday, October 16th.

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 a 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. I told Dr. Waldman, "clearly, 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. Then, in 2014, we sent a little girl named Cecelia Price to Milan. Since then, we have 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 for 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. As it happens, nature offered a perfect 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 and rather bold solution: HIV. Biffi 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, so we can find children in time to get them these treatments that repair broken genes. 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 Cal's 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.