Skip to Main Content

When GlaxoSmithKline, long a global leader in the effort to pioneer gene replacement therapies, announced it would halt its drug development program for rare diseases, I understood that the decision made practical sense for the company. But as the mother of a child with a rare disease — one for which GSK was developing a highly effective treatment — I was devastated.

My daughter, Cal, was diagnosed with metachromatic leukodystrophy (MLD) at age 2. Within three months, she lost the ability to walk, talk, and eat. She uttered her final word — “Daddy” — five years ago. Now age 8, Cal is paralyzed, blind, and receives hospice care. We are grateful she still laughs and smiles.


MLD is caused by a mutation in a single gene. That error causes fats known as sulfatides to accumulate in cells. An abundance of sulfatides in cells that make myelin, the substance that insulates and protects nerves, causes progressive destruction of tissue throughout the brain, spinal cord, and other parts of the nervous system.

Not long after Cal was diagnosed, I learned that GlaxoSmithKline had licensed research on gene therapy for MLD from the Telethon Institute in Milan. GSK’s involvement in a disease that affects just 1 in every 100,000 children born (about 1,300 children around the globe each year) gave me hope. Learning that one of the largest pharmaceutical companies on the planet was going to take on your kid’s ultra-rare disease was like having your big brother stand up to a schoolyard bully.

Experts in the field called the results from GSK’s clinical trials of gene therapy for MLD “stunning.” Children who should have been unable to talk or walk, who needed feeding tubes and hospice care, were instead attending school and riding bicycles and living remarkably normal lives.


MLD Kids
Children with MLD who have been helped by a new gene therapy attend a Calliope Joy Foundation event. Courtesy Peter Kurilla

Workers at GSK took tremendous pride in the project. When I was invited to the company’s U.S. headquarters in suburban Philadelphia and told researchers and other GSK employees about the hope that gene replacement therapy was bringing to families, there was hardly a dry eye in the house.

I pointed out that published papers could not show the amazing things I had witnessed, like kids with MLD eating hot dogs, running outside, and talking to their parents. They were getting a chance to grow up because of the work GSK was doing.

As a patient advocate, I appreciated that the members of the rare disease team answered my phone calls, circulated my memos, and endured my nagging and prodding to get gene therapy for MLD to the U.S. sooner rather than later. They understood that I had to be relentless because I was acting as a champion for Cal and others like her. I was also honoring kids with MLD who died before getting a chance to take advantage of this breakthrough therapy. I make it a point to write letters to their parents, promising that I will not stop until gene therapy for MLD is available to children in the U.S.

When I learned that Emma Walmsley, GSK’s chief executive officer, had decided to divest the company of its gene therapy assets for MLD, along with those for severe combined immunodeficiency due to adenosine deaminase deficiency and for Wiskott-Aldrich syndrome, it felt like GSK was abandoning families like ours.

Walmsley wants the company to focus on “real winners” — medicines that generate substantial returns. She’s correct in her assessment that GSK would have had trouble making money on gene therapy for MLD. These kinds of therapies have astronomical price tags, ranging from $300,000 to $1 million per patient. Payers and politicians will balk at paying six figures for a treatment we are still finding the words to describe. Companies will struggle to construct sustainable business models for these treatments in the years to come.

I get that. But the decision that gene therapy for MLD wasn’t worth GSK’s time and resources seemed to suggest that Walmsley didn’t fully understand the great value of what GSK had already accomplished in developing this therapy.

Metachromatic leukodystrophy was teaching GSK researchers how they could tame HIV to build lentiviral vectors. This means stripping HIV of its harmful properties, adding to it working copies of the failed gene that causes MLD, and using the virus to deliver that gene to children with the disease.

GSK researchers understood that if they could stop MLD in this way, they would be able to take on thousands of other disorders caused by a single faulty gene.

Ironically, one of the goals for GSK under Walmsley’s leadership is to pursue the admirable aim of treating HIV/AIDS. I’m not sure why she didn’t seem to appreciate how the company was already using the virus that causes this disease to save children’s lives and conquer other diseases.

Sticking with its rare disease drug development program for a while longer would have been a bit of a financial sacrifice for GSK. But I must point out the huge sacrifices that MLD families have already made to advance this research.

Gene therapy needs time to take effect. It doesn’t work for children with symptoms of MLD, like my daughter Cal. It works only in children who are diagnosed with the disease before it begins causing any trouble.

MLD is so rare that children aren’t tested for it at birth. It’s discovered only when a child develops symptoms, which is too late to begin gene therapy. But his or her younger siblings can be tested for the disease and treated if they have it. Imagine a clinical trial in which most every family watched one child succumb to the disease while they fought to save another.

I wish that Walmsley had the chance to meet children with MLD whose lives were saved and forever changed by the gene therapy her company developed. Had that happened, I suspect she would have felt differently about research she did not believe was a “winner.” She would have realized that GSK had something that was far better: a miracle.

Maria Kefalas is a professor of sociology at Saint Joseph’s University in Philadelphia and co-founder of the Calliope Joy Foundation. She writes about her work as a patient advocate and her experiences with MLD at The Calliope Joy Foundation blog, where an earlier version of this article appeared, and is working on a memoir about her life as a patient advocate, to be published by Beacon Press in 2020.

Comments are closed.