{"id":3882,"date":"2017-05-03T20:20:38","date_gmt":"2017-05-03T20:20:38","guid":{"rendered":"https:\/\/lpfch.org\/bubble-boy-2-0\/"},"modified":"2024-02-14T14:07:37","modified_gmt":"2024-02-14T14:07:37","slug":"bubble-boy-2-0","status":"publish","type":"post","link":"https:\/\/lpfch.org\/hy\/impact-stories\/bubble-boy-2-0\/","title":{"rendered":"\u0532\u0561\u0562\u056c \u0532\u0578\u0575 2.0"},"content":{"rendered":"

Maria Grazia Roncarolo, MD, has already cured “Bubble Boy” disease. What incurable disease will she cure next? <\/strong><\/p>\n

Fixing a single gene gave a child back the immune system he’d lacked at birth, allowing him to function normally in a dirty world within a year of treatment. <\/p>\n

That mission accomplished, Maria Grazia Roncarolo, MD, left Italy’s top medical research job and came to Stanford University in 2014. Here she’s leading efforts to fast-track stem cell and gene therapy out of the laboratory and into clinical trials. This year, she launched Stanford’s ambitious new Center for Definitive and Curative Medicine. <\/p>\n

In this Q&A, Roncarolo, professor of pediatrics and of medicine, talks about her Center’s urgent near-term goal: to fully cure another 50 diseases ASAP, beginning with sickle cell anemia. <\/p>\n

Philanthropists, start your engines. It won’t be cheap. <\/strong><\/em><\/p>\n

Why did you go into medicine in the first place? <\/strong>
My husband always says, “Maria Grazia went around the world to pursue her dream, which was to cure patients with incurable diseases. And in the journey she encountered her husband and produced two beautiful children.” That’s how he always introduces me. And it’s true! <\/p>\n

[She laughs, then turns serious.] <\/p>\n

From when I was a medical student, I was exposed to the situation where many of these children, we just had to say to the parents, “Sorry. We cannot do anything for your child.” And that was incredibly frustrating. <\/p>\n

It was in my mind when I was even a teenager: to really make a difference for people who are sick. And the idea was always for children. <\/p>\n

Were you “destined” for a medical career? <\/strong>
I come from a family of business people. My father had a completely different agenda for me. He expected me to head the research depart¬ment at the family-owned company [industrial paints for cars]. Unfortunately the problem was solved because he passed away when I was in my last year of high school. <\/p>\n

My mother and my elder sister who took over the company said, “The worst thing you can do to yourself is to go into a job where you don’t have the passion.” <\/p>\n

So they gave me a green light. Especially my elder sister, who’d just gotten her MBA. I am the only one in my family who’s in the medical field. And this was something unexpected for my family.<\/p>\n

In March 2017, news from Paris reported the first patient cured of sickle cell anemia through an experimental gene therapy, in which bone marrow stem cells were extracted from the boy, altered so that they would make normal hemoglobin, and then put back into the boy’s body. Was that the same technique you pioneered in Italy? <\/p>\n

It’s a similar approach. <\/p>\n

But I can tell you that what we’re doing here now at Stanford is much more advanced. <\/p>\n

Don’t get me wrong: the old approach works! But it needs to be rendered more precise to be broadly useful. The major problem with the old approach? We never know where this healthy gene lands in the genome of the cells. <\/p>\n

It’s like, you have a genetic dictionary with many words. And there is one word that is misspelled and you put the correct word back in randomly all over the dictionary, without alphabetical order. That’s the best example I can give. <\/p>\n

So what Dr. Matt Porteus does here at Stanford with genome editing is very different. Because what we do is remove the misspelled word from the dictionary and replace it with the correct gene, the correct word, exactly in the same position as it should be. <\/p>\n

In 2018, there will start to be clinical trials? <\/strong>
Correct. You know, severe combined immunodeficiency, what we call “bubble boy” disease, is very rare. But sickle cell anemia is a nasty disease that affects millions of people worldwide, including certain populations of people [in India and Africa] who do not have access to medical services. This could make a big difference. <\/p>\n

Currently, sickle cell can be treated with stem cell transplantation, but this therapy comes at a high cost for the patient’s quality of life. For at least six months, he needs to be protected. He cannot go to school. He cannot play with other children. He cannot live in a normal household. And it comes with a risk of mortality. <\/p>\n

If we can come in with an approach that is curative, without the toxicity and risk of the stem cell transplantation that we do today, it would be a major benefit. <\/p>\n

The precision medicine approach here at Stanford is really the future of gene therapy. We are working very, very intensively to bring sickle cell treatment to the clinical stage next year. <\/p>\n

During the clinical stage, a potential cure is tested on humans to prove its worth and uncover any side effects. Clinical trials are a prerequisite for approval by federal regulators. <\/p>\n

Where are we going to be in five years? <\/strong>
The potential at Stanford is unique. And when I say unique, I mean unique in the world. <\/p>\n

Because when you look at the incredible science that is done in this building [the Lorry I. Lokey Stem Cell Research Building], and not only in this building, but throughout the School of Medicine and in other schools, it’s unique. <\/p>\n

Yet when you look at how much of this science is translated into novel therapies for children, it’s not proportional. <\/p>\n

So I felt that if I could really close this gap—what scientists call the Valley of Death, between the fundamental discovery and the cure—we could make a difference for many children with incurable diseases. <\/p>\n

We have in the pipeline about 15 clinical trials that we can start in the next three to five years in cancer, genetic diseases of the blood and immune system, autoimmune diseases such as diabetes or chronic inflammatory diseases, skin defects such as epidermolysis bullosa, and metabolic diseases. Each of these clinical trials would cost at least $10 million to show safety and efficacy—to close the Valley of Death. <\/p>\n

What’s your dream? <\/strong>
To cure what is curable, and to make curable what is not. <\/p>\n

You know, if we think to the future and we dream a little bit, I always say the ideal situation is to perform a newborn screening for a genetic disease, and then to cure it in the newborn. And if you want to go one step further, maybe 10 or 15 years from now, we will diagnose and repair the defect in utero. <\/p>\n

Ultimately, you want to have a patient that never becomes a patient. <\/p>\n

In 2017, the MIT Technology Review featured Dr. Maria Grazia Roncarolo’s work in its annual review of “breakthrough technologies.” In an article titled Gene Therapy 2.0, the review wrote: “Scientists have solved fundamental problems that were holding back cures for rare hereditary disorders. Next we’ll see if the same approach can take on cancer, heart disease, and other common illnesses.” <\/p>\n

We have to ask: Do you have hobbies? <\/strong>
OK, now I go full disclosure: my job is my passion. And I think that I’ve been incredibly lucky. <\/p>\n

My children know about my job. They know about the science and the patients I treated. They were engaged in that all the way. <\/p>\n

My husband is also a scientist. He understands what it takes. And he could tolerate a wife who was always very busy. And when she was not busy, she was exhausted. [Laughs again.] <\/p>\n

I’m a woman. I have two children; a husband who has been with me 30 years. And a job that is a passion. There was no space for anything else. <\/p>\n

People say to me, “Oh, this was a big sacrifice for you.” <\/p>\n

Not really. It was not a sacrifice. It was a choice. <\/p>\n

I lived in the Bay Area from ’89 to ’97. That is not a short period of time. <\/p>\n

People say to me, “Oh, you went to Yosemite.” I say, “No, we didn’t.” <\/p>\n

“Oh, you went to Big Sur.” I say, “No, we didn’t.” <\/p>\n

“Oh, you went to Las Vegas.” “No, we didn’t.” <\/p>\n

They would go on and on and on. “You went to Cabo San Lucas.” “No, we didn’t.” 
“What did you do?” <\/p>\n

I worked. And I produced two children. [Laughing.] <\/p>\n

My sister says, “Maria Grazia, how do you live?” I live as I choose to live. I have two beautiful children who are amazingly balanced despite this mom who was always busy, busy, busy. And I have the incredible luck to have a job that is a passion.<\/p>\n

This article first appeared in the Spring 2017 issue of Lucile Packard Children's News<\/a>.<\/em><\/p>\n

SCIENCE FICTION? Explore the potential of stem cell and gene therapy at supportLPCH.org\/cdcm<\/a>.<\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"

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