Tag Archive for: Gene therapy

Clumps of sickle cell blocking a blood vessel

The future of sickle cell disease treatment through gene therapy

Clumps of sickle cell blocking a blood vessel

In a new review article published in The CRISPR Journal, researchers from Children’s National Hospital discuss the progress of gene therapies for sickle cell disease – from preclinical studies to clinical trials and FDA approval – along with the many challenges of these treatments.

Over the past few years, the advances of gene therapy for sickle cell disease (SCD) offer a potential cure for a condition previously managed only through symptom relief and limited treatments. SCD is a hereditary blood disorder caused by a mutation in the beta globin gene leading to painful symptoms and complications.

In a new review article published in The CRISPR Journal, researchers from Children’s National Hospital discuss the progress of gene therapies for SCD – from preclinical studies to clinical trials and FDA approval – along with the many challenges of these treatments.

“We are hoping to bring attention to the past, present and future of this topic,” says Henna Butt, MD, pediatric hematology oncology fellow at Children’s National and one of the review authors. “It is exciting to see the technology move forward and see how far we have come in a disease where so little progress has been made historically.”

The hold up in the field

Gene therapy for SCD remains a time- and resource-intensive process, often taking several months from the initial patient consultation to treatment.

“Progress in SCD gene therapy has been slowed by high costs, limited accessibility and safety concerns, such as off-target effects,” says Dr. Butt. “Additionally, long-term efficacy data is still needed to confirm the durability of these treatments. Regulatory hurdles and ethical considerations also contribute to the delays.”

Moving the field forward

“By using cutting-edge techniques like CRISPR and base editing to directly correct the genetic mutation responsible for SCD, these therapies have the potential to offer long-term or even permanent relief,” says Dr. Butt. “Success in this area could revolutionize treatment options, improve patient outcomes and reduce the global burden of SCD — especially as therapies become more accessible and affordable.”

“Advancing gene therapy for sickle cell disease requires not just scientific innovation, but also the clinical expertise and systems to deliver it safely and effectively,” says David Jacobsohn, MD, SCM, MBAD, chief of Bone and Marrow Transplantation at Children’s National. “As access expands, we must ensure these therapies reach the patients who need them most.”

The patient benefit

Gene therapy offers a potential cure for SCD, reducing the need for ongoing treatments and significantly improving quality of life. It can lower the risk of complications and infections, and over time, reduce healthcare costs – especially for patients with limited access to traditional care. Raising awareness of current challenges can help drive advocacy for affordability and access.

Children’s National leads the way

Children’s National was the first hospital in the world to collect stem cells for the LYFGENIA™ treatment and one of the few pediatric hospitals in the country that offers both FDA-approved sickle cell disease gene therapies – CASGEVY™ (exagamglogene autotemcel) and LYFGENIA™ (lovotibeglogene autotemcel).

Additional authors from Children’s National include: Mamatha Mandava, MD, and David Jacobsohn, MD, SCM, MBA

Read the full review published in The CRISPR Journal.

Experts from Children’s National Hospital at the 2025 Tandem Meetings

Children’s National experts at the 2025 Tandem Meetings

Experts from Children’s National Hospital at the 2025 Tandem Meetings

Nurse Practitioner Sameeya Ahmed-Winston, CPNP, CPHON, was recognized with the APP Lifetime Achievement Award.

Experts from Children’s National Hospital presented and showcased their latest research at the 2025 Tandem Meetings in Hawaii.

This leading global conference on hematopoietic cell transplantation (HCT), cellular therapy and gene therapy brings together top specialists to share groundbreaking discoveries, innovative technologies and the latest scientific advancements shaping the field.

Fellow Henna Butt, MD, won Best Abstract for her research paper – Comparative Analysis of CRISPR-Cas9, Lentiviral Transduction and Base Editing for Sickle Cell Disease Therapy in a Murine Model.

Nurse Practitioner Sameeya Ahmed-Winston, CPNP, CPHON, was recognized with the APP Lifetime Achievement Award.

Additional presenters:

These achievements highlight Children’s National Hospital’s commitment to advancing research and improving treatments for patients with complex conditions. By sharing their expertise on a global stage, these specialists help shape the future of patient care and improve outcomes for children worldwide

Read more highlights from the 2025 Tandem Meetings here.

Kendric receives care at Children's National.

Rewriting the script for sickle cell disease

More than 100,000 Americans have sickle cell disease, an inherited blood disorder that can cause excruciating pain crises and shorter life expectancies.

Children’s National has one of the largest sickle cell programs in the United States. We are pioneering treatments and provide specialized care to about 1,500 patients each year. We participate in clinical trials to improve outcomes, shorten treatment time, reduce complications and minimize the need for opioids and chemotherapy.

Kendric receives care at Children's National.

Kendric receives care at Children’s National.

In recognition of our clinical and research excellence, Children’s National was one of a few U.S. pediatric hospitals selected to offer two promising new FDA-approved gene therapies.

Hematologist Robert Sheppard Nickel, M.D., leads a study to reduce toxicities in bone marrow transplants. “Years of development led to these curative therapies,” Dr. Nickel says. “I hope in the future we can safely cure more children with sickle cell disease.”

“The future looks promising to revolutionize the lives of our patients and make these therapies accessible worldwide,” says Andrew Campbell, M.D., director of our Comprehensive Sickle Cell Disease Program.

Kendric and Nasir find hope

In May 2024 at Children’s National, 12-year-old Kendric of Clinton, Maryland, became the world’s first patient with sickle cell disease to begin a commercially approved gene therapy that could dramatically reduce or even eliminate his pain. It involved extracting his bone marrow stem cells; genetically modifying them in a specialized lab to reduce the risk of sickling; and then, after chemotherapy, infusing them back into his bloodstream.

Expert, compassionate care empowered Kendric to understand the science behind his treatment and chart a path to recovery. “My care team taught me how to deal with my disease and everything that I need to know for the future,” he says. “They gave me hope that I could be cured.”

Nasir and his care team

Nasir and his care team.

Nasir, age 20, spent his childhood waiting to find a match for a stem cell transplant to address his sickle cell disease. Finally, in 2023, at Children’s National, he found an answer in gene therapy to alter his own cells.

Due to painful episodes and the need for frequent blood transfusions, both Kendric and Nasir missed out on a lot of school, important moments with friends and simply being kids. Now, they can explore a world in which patients like themselves can overcome this disease and reclaim their health.

“I have all of this oxygen and energy that came out of nowhere,” Nasir says. “It’s really a new life. I feel reborn.”

“The network of doctors at Children’s National gave us reassurance and lots of hope,” says Kendric’s mom, Deborah. “They made us feel like family. We are in awe of how quickly things moved and how much compassion they have shown us.”

Read more stories like this one in the latest issue of Believe magazine.

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Children’s National in the News: 2024

collage of news logosIn 2024, Children’s National Hospital continued to make remarkable strides across diverse areas of pediatric medicine, from groundbreaking technological innovations to critical health advocacy. The following compilation showcases ten significant stories that demonstrate the breadth and depth of the hospital’s impact, as featured in major national news outlets including NBC Nightly News, CNN, The Washington Post, The New York Times, NPR, The Today Show, Healio, and POLITICO. Delve into our 2024 news highlights for more.

1. World’s smallest pacemaker gives new hope to babies with heart defects

Charles Berul, M.D., and a patient family talk about the pill-sized pacemaker that saved the life of Abby, an infant born with deadly heart defects. (NBC Nightly News)

2. ‘A $10 death trip’: Fentanyl is killing teens. Meet one fighting for his life

Sivabalaji Kaliamurthy, M.D., addiction psychiatrist and director of the Addictions Program, spoke to CNN about the impact of drug addiction on teen health and the lack of resources available to treat opioid use disorder. (CNN)

3. Health panel urges interventions for children and teens with high BMI

Susma Vaidya, M.D., M.P.H., associate medical director of the IDEAL Clinic, shared her concerns about childhood obesity treatment recommendations issued today by a leading panel of independent U.S. health experts. (The Washington Post)

4. An Rx for food? Doctor’s offices offer groceries to those in need

Shideh Majidi, M.D., M.S.C.S., and Emily Frymark, clinical dietitian, spoke about how the food pharmacy, created in partnership with the Capital Area Food Bank, benefits patients with diabetes and other chronic conditions. (The Washington Post)

5. First patient begins newly approved sickle cell gene therapy

Kendric Cromer, a 12-year-old boy being treated at Children’s National Hospital, became the first person in the world with sickle cell disease to begin a commercially approved gene therapy that may cure the condition. “This is a big effort,” says David Jacobsohn, M.D., ScM, M.B.A. (The New York Times)

6. ‘We created this problem’: A pediatric surgeon on how gun violence affects children

Mikael Petrosyan, M.D., associate chief of General and Thoracic Surgery, discusses the stress medical staff face when treating young victims of gun violence. (NPR)

7. 7th grade boy rings bell after final round of chemotherapy

Landon, an 11-year-old patient, rang the bell at Children’s National Hospital with family, friends, doctors and nurses cheering after finishing his final round of chemotherapy. (The Today Show)

8. Study: One in three adolescents experience ‘period poverty’

Monika Goyal, M.D., M.S.C.E., pediatric emergency medicine specialist and co-director of the Center for Translational Research, emphasized the need for awareness in addressing period poverty in teenagers and young adults. (Healio)

9. The AI assurance labs are coming

Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., vice president and chief innovation officer, participates in a panel discussion covering AI data collection, associated risks, reliance and other topics related to artificial intelligence. (POLITICO)

10. First day of a ‘new life’ for a boy with sickle cell

Children’s National patient Kendric Cromer, 12, became one of the first children ever to be treated with a newly approved gene therapy that will free him from the sickle cell disease that has stolen his childhood. (The New York Times)

Dr. Andrew Campbell

Meet Dr. Andrew Campbell: Trailblazing treatment for patients with sickle cell disease

Andrew Campbell, M.D., remembers the first time he met a patient with sickle cell disease in the early years of his medical training. It was a brief interaction that had a profound effect on the trajectory of his career.

Sickle cell disease is an inherited blood disorder that primarily affects African American and Hispanic American children. The disease can cause severe pain events as well as progressive organ damage in patients.

This life-altering disease has affected children for more than a century, yet only one FDA-approved drug for treatment of sickle cell disease was developed in the first 100 years of its existence. Recognizing the health inequities that have contributed to an overall lack of therapies and providers in the field, Dr. Campbell knew he had to act.

“It was an area that needed a lot of resources, but also a lot of research and understanding of what our patients are going through. So, that was my initial launch into the field of Hematology and Oncology,” he explained, and he’s been an instrumental leader ever since.

For the past seven years, Dr. Campbell has served as the director of the Comprehensive Sickle Cell Disease Program at Children’s National Hospital — one of the largest sickle cell programs in the country, treating nearly 1,400 patients a year. Locally, he is Principal Investigator for the American Society of Hematology Sickle Cell Research Collaborative’s DMV Sickle Cell Consortium that includes several area sickle cell clinics including Northern Virginia, Richmond, Washington DC and Maryland.

In December 2023, the FDA approved two new gene therapies (CASGEVY™ and LYFGENIA™) to treat patients with sickle cell disease. Children’s National became one of the few pediatric hospitals in the country to offer these therapies, going on to then treat the first patient in the U.S. using the gene therapy method.

Dr. Campbell, who is treating the 12-year-old patient, says his team is excited about the future of these non-chemotherapy treatments and the curative possibilities they will bring to the field.

Despite being part of this significant milestone in the sickle cell community, Dr. Campbell says the work doesn’t stop there. His passion for making a difference and his impact on patients extends far beyond just Washington, D.C., and even the U.S.

For example, Dr. Campbell directs a research group called the Consortium for the Advancement of Sickle Cell Disease Research (CASiRe), with other sickle cell providers across the world. He says one of their goals is to better understand the ways that sickle cell can present itself in patients based on the country in which they receive treatment. “It’s really showing that based on the geographic difference of patients, it has implication in how they receive care,” he explains, adding that the group hopes to take what they learn in these studies to design more inclusive clinical trials in the future.

When he’s not devoting his time to research, you can find Dr. Campbell taking the fight for patients with sickle cell disease directly to lawmakers.

“I have gone to Capitol Hill a number of times to advocate for access and improvement of treatments for sickle cell disease,” he says, hoping that by using his voice and presenting his research, he can help the current generation, as well as the future generation of patients, get the care they deserve.

Assessing psychosocial risk, patient readiness for sickle cell gene therapy

The CureSCi Patient Readiness and Resilience Working Group brought together behavioral health clinicians and scientists from across the U.S. with expertise in sickle cell disease to develop recommendations for assessing and promoting patient readiness for gene therapy.

Two gene therapies for sickle cell disease were recently approved by the U.S. Food and Drug Administration (FDA) and are now commercially available in the U.S. This marks a historic shift in the treatment of sickle cell disease (SCD) and represents a leap forward more broadly for the medical community, opening a range of exciting possibilities for the development of novel therapeutics for other diseases. However, these new therapies are not without medical and psychological risks; therefore, the Cure Sickle Cell Initiative (CureSCi) of the National Heart, Lung and Blood Institute (NHLBI) convened a Patient Readiness and Resilience Working Group to develop recommendations for the assessment of psychosocial readiness for gene therapy.

What’s been the hold-up in the field?

Clinicians have long recognized that psychological and social issues have the potential to affect treatment outcomes following disease-modifying or transformative treatments, such as hematopoietic stem cell transplants. The same concerns exist for gene therapies, but there has not been clear guidance about the best ways to evaluate patient readiness and psychosocial risk and resilience factors in these contexts.

How does this work move the field forward?

The CureSCi Patient Readiness and Resilience Working Group brought together behavioral health clinicians and scientists from across the U.S. with expertise in SCD, as well as caregivers and patients with the lived experience of having SCD, to develop recommendations for assessing and promoting patient readiness for gene therapy. The resulting consensus statement outlines clear and practical guidance for conducting pre-gene therapy patient readiness assessments.

“This is an exciting time for the sickle cell and medical communities,” says Steven Hardy, Ph.D., director of Behavioral Health Services in the Divisions of Hematology, Oncology and Blood and Marrow Transplantation at Children’s National Hospital and lead author on the consensus statement. “But it is also a time to exercise caution to ensure that, in the cloud of such enthusiasm, we do not lose sight of the complex ways that human psychology, relationships and biology interact to influence health.”

How will this work benefit patients?

This new guidance for evaluating psychosocial readiness will ensure that important issues — such as the degree to which patients have been informed of and understand key treatment details, are interested in and motivated to pursue treatment, and have considered how undergoing gene therapy will affect their activities, relationships and mental health — are considered and patients are provided the necessary supports.

“These recommendations offer a blueprint and a charge to institutions, payors and policymakers around the world to prioritize the psychosocial well-being of patients with SCD undergoing gene therapy,” says Dr. Hardy.

How is Children’s National leading in this space?

Children’s National has participated in gene therapy clinical trials and is the first institution globally to treat a patient with SCD with one of the new commercially available gene therapies. Dr. Hardy chaired the CureSCi Patient Readiness and Resilience Working Group that developed the consensus recommendations. Psychologists in the Divisions of Hematology, Oncology and Blood and Marrow Transplantation have adopted a standard protocol, informed by the consensus recommendations, for conducting pre-gene therapy assessments of patient readiness.

You can read the full consensus statement, Assessing Psychosocial Risk and Resilience to Support Readiness for Gene Therapy in Sickle Cell Disease: A Consensus Statement, in JAMA Network Open.

researchers in a lab at Children's National

Pioneering gene therapy as a treatment for sickle cell disease

Gene therapy is a new and exciting treatment option available for patients with sickle cell disease (SCD). Children’s National Hospital is one of the few pediatric hospitals in the country that offers both FDA-approved sickle cell disease gene therapies: CASGEVY™ (exagamglogene autotemcel) and LYFGENIA™ (lovotibeglogene autotemcel).

What this means

Gene therapy involves an autologous transplant, taking the patient’s own stem cells, genetically changing those stem cells and then, after chemotherapy, infusing those stem cells back into the patient to make healthy blood.

“I’m excited about gene therapy for sickle cell disease. I think it has the potential to be a curative option for every single child with sickle cell disease,” said Robert Nickel, M.D., hematologist at Children’s National.

Currently both treatments are only approved for patients 12 years and older with severe disease. Children’s National was the first hospital in the world to collect stem cells for the LYFGENIA™ treatment.

Moving the field forward

Clinical trials hold incredible promise to advance the care of SCD. Children’s National continues to pioneer transplant therapies to cure SCD and is one of the leading centers participating in clinical trials of new treatments for this condition.

Experts at Children’s National are leading a multi-site clinical trial of a chemotherapy-free transplant approach for SCD using a matched sibling donor. This chemotherapy-free approach has less toxicity and side effects for children undergoing transplant.

In addition, Children’s National has been leading the way with innovative approaches to support sickle cell patients. “We’re providing alternative approaches to pain such as healing touch, acupuncture, massage VR technology, physical therapy and exploring other ways of treating pain in an integrated manner,” said Andrew Campbell, M.D., director of the Comprehensive Sickle Cell Disease Program at Children’s National.

The team is also exploring non-opioid treatments, such as intravenous citrulline, a naturally occurring amino acid that has been proven to enhance blood flow and potentially alleviate pain in treated patients in preliminary studies under the direction of Suvankar Majumdar, M.D., chief of Hematology at Children’s National.

illustration of sickled blood cells

Children’s National experts showcase sickle cell disease research

illustration of sickled blood cellsAndrew Campbell, M.D., director of the Comprehensive Sickle Cell Disease program, assessed the lifetime value of cell and gene therapy (CGTS) through a case study at The American Society of Gene and Cell Therapy’s (ASGCT) Annual Meeting.

Dr. Campbell and other Children’s National researchers will be presenting again at the Foundation for Sickle Cell Disease Research’s (FSCDR) Annual Sickle Cell Disease Research and Educational Symposium, June 7-9, 2024. The symposium includes more than 500 leading researchers, physicians, clinicians and social workers from all over the world.

Here’s a look at the presentations from Children’s National:

Day Time Presenter(s) Title
Sunday, June 9, 2024 8:00 AM – 9:15 AM Andrew Campbell, M.D. Update on Sickle Cell Legislation in the US

 
Sunday, June 9, 2024 3:00 PM – 3:15 PM Andrew Campbell, M.D., Deepika Darbari, M.D., and Regine Hyppolite, MSA Diagnostic Potential of Platelet-Neutrophil Ratio (PNR) for Stroke Risk in SCD Children

 
Sunday, June 9, 2024 3:15 PM – 3:30 PM

 

 Andrew Campbell, M.D. A Pilot Study to Increase Naloxone Education and Prescriptions in Sickle Cell Clinics

 
Sunday, June 9, 2024 4:00 PM – 4:15 PM Steven Hardy, Ph.D. Correlation Between VOC and Cognitive Function Using The NIH ToolBox in SCD
Sunday, June 9, 2024 4:15 PM – 4:30 PM

 

 

 Andrew Campbell, M.D., Deepika Darbari, M.D., and Regine Hyppolite, MSA Platelet to neutrophil ratio as a novel marker for monitoring SCD patients on hydroxyurea

 

 

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Children’s National in the News: 2023

collage of news outlet logos
Explore some of the notable medical advancements and stories of bravery that defined 2023, showcasing the steadfast commitment of healthcare professionals at Children’s National Hospital and the resilient spirit of the children they support. Delve into our 2023 news highlights for more.

1. COVID during pregnancy dramatically increases the risk of complications and maternal death, large new study finds

According to a study published in British Medical Journal Global Health, women who get COVID during pregnancy are nearly eight times more likely to die and face a significantly elevated risk of ICU admission and pneumonia. Sarah Mulkey, M.D., prenatal-neonatologist neurologist, discussed findings based on her work with pregnant women and their babies.
(Fortune)

2. Rest isn’t necessarily best for concussion recovery in children, study says

A study led by Christopher Vaughan, Psy.D., pediatric neuropsychologist, suggests that — despite what many people may presume — getting kids back to school quickly is the best way to boost their chance for a rapid recovery after a concussion.
(CNN)

3. Pediatric hospital beds are in high demand for ailing children. Here’s why

David Wessel, M.D., executive vice president, chief medical officer and physician-in-chief, explained that one reason parents were still having trouble getting their children beds in a pediatric hospital or a pediatric unit after the fall 2022 respiratory surge is that pediatric hospitals are paid less by insurance.
(CNN)

4. Anisha Abraham details impact of social media use on children: ‘True mental health crisis’

Anisha Abraham, M.D., M.P.H., chief of the Division of Adolescent and Young Adult Medicine, joined America’s Newsroom to discuss the impact social media access has had on children’s mental health.
(FOX News)

5. Saving Antonio: Can a renowned hospital keep a boy from being shot again?

After 13-year-old Antonio was nearly killed outside his mom’s apartment, Children’s National Hospital went beyond treating his bullet wounds. Read how our Youth Violence Intervention Program team supported him and his family during his recovery.
(The Washington Post)

6. Formerly conjoined twins reunite with doctors who separated them

Erin and Jade Buckles underwent a successful separation at Children’s National Hospital. Nearly 20 years later they returned to meet with some of the medical staff who helped make it happen.
(Good Morning America)

7. Asthma mortality rates differ by location, race/ethnicity, age

Shilpa Patel, M.D., M.P.H., medical director of the Children’s National IMPACT DC Asthma Clinic, weighed in on a letter published in Annals of Allergy, Asthma & Immunology, asserting that the disparities in mortality due to asthma in the United States vary based on whether they occurred in a hospital, ethnicity or race and age of the patient.
(Healio)

8. How one Afghan family made the perilous journey across the U.S.-Mexico border

After one family embarked on a perilous journey from Afghanistan through Mexico to the U.S.-Mexico border, they eventually secured entry to the U.S. where Karen Smith, M.D., medical director of Global Services, aided the family’s transition and provided their daughter with necessary immediate medical treatment.
(NPR)

9. When a child is shot, doctors must heal more than just bullet holes

With the number of young people shot by guns on the rise in the U.S., providers and staff at Children’s National Hospital are trying to break the cycle of violence. But it’s not just the physical wounds though that need treating: young victims may also need help getting back on the right track — whether that means enrolling in school, finding a new group of friends or getting a job.
(BBC News)

10. This 6-year-old is a pioneer in the quest to treat a deadly brain tumor

Callie, a 6-year-old diagnosed with diffuse intrinsic pontine glioma, was treated with low-intensity focused ultrasound (LIFU) at Children’s National Hospital and is the second child in the world to receive this treatment for a brain tumor. LIFU is an emerging technology that experts like Hasan Syed, M.D., and Adrianna Fonseca, M.D., are trialing to treat this fatal childhood brain tumor.
(The Washington Post)

11. F.D.A. approves sickle cell treatments, including one that uses CRISPR

The FDA approved a new genetic therapy, giving people with sickle cell disease new opportunities to eliminate their symptoms. David Jacobsohn, M.B.A., M.D., confirmed that Children’s National Hospital is one of the authorized treatment centers and talked about giving priority to the sickest patients if they are on Vertex’s list.
(The New York Times)

12. 6-year-old fulfils wish to dance in the Nutcracker

After the potential need for open-heart surgery threatened Caroline’s Nutcracker performance, Manan Desai, M.D., a cardiac surgeon, figured out a less invasive procedure to help reduce her recovery time so she could perform in time for the holidays.
(Good Morning America)

Hiram receives the first commercial dose of Elevidys

Children’s National gives first commercial dose of new FDA-approved gene therapy for Duchenne muscular dystrophy

Hiram receives the first commercial dose of Elevidys

On the day before his 6th birthday, Hiram, 5, was the first patient ever with DMD to receive the drug after the U.S. Food and Drug Administration (FDA) approved its use last month.

Children’s National Hospital is the first pediatric hospital to administer a commercial dose of Elevidys (delandistrogene moxeparvovec-rokl), the first gene therapy for the treatment of pediatric patients with Duchenne muscular dystrophy (DMD).

On the day before his 6th birthday, Hiram, 5, was the first patient ever with DMD to receive the drug after the U.S. Food and Drug Administration (FDA) approved its use last month.

“The approval of Elevidys opens a new door for young patients with DMD and their families,” says Sarah Wright, D.O., neuromuscular neurologist at Children’s National. “This disease has had limited targeted treatments to date which can help alter the trajectory of disease.”

The background

On June 22, the FDA approved the use of Elevidys for patients 4 through 5 years of age with DMD with a confirmed mutation in the DMD gene who do not have a pre-existing medical reason preventing treatment with this therapy.

DMD is a rare and progressive genetic neuromuscular disease that predominantly affects males. It is caused by genetic changes in the DMD gene that affects the muscles, leading to muscle wasting that gets worse over time. Symptoms include progressive weakness and loss (atrophy) of both skeletal and heart muscle. Muscle weakness is usually noticeable in early childhood when signs like delayed ability to sit, stand or walk, and difficulties learning to speak manifest in a patient.

How it works

Elevidys is a one-time intravenous gene therapy that aims to delay or halt the progression of DMD by delivering a modified, functional version of dystrophin to muscle cells. The dystrophin gene is the largest known human gene.

“Elevidys is a viral vector (the ‘envelope to deliver the gene of interest’) mediated gene therapy that allows for the introduction of a gene that codes for a shortened form of dystrophin protein, or microdystrophin,” Dr. Wright explains. While not a cure for DMD, trials of Elevidys have demonstrated increases in dystrophin expression and improved functional results in young children with the disease.

“We have years of dedicated work on the part of researchers, clinician leaders and advocacy organizations in the field of muscular dystrophy to thank for this ground-breaking moment,” says Dr. Wright. “The approval of Elevidys offers families of patients ages 4-5 with DMD the option to receive this gene therapy that is designed to target the underlying cause of the disease.”

“The time-sensitivity of this medication illustrates the importance of going to a top academic pediatric hospital early on in neurologic care,” adds Elizabeth Wells, M.D., senior vice president of the Center for Neuroscience and Behavioral Medicine at Children’s National.

What’s next

The neuromuscular team at Children’s National is looking forward to offering this therapy to young patients with DMD and to the completion of additional trials/results for therapies in the DMD drug development pipeline.

“The research and approval of novel therapies provides more options for our DMD patients and their families, which is a critical step toward improving the lives of patients with DMD,” Dr. Wright says.

Microscopic view of thalassemia

What it means to be a designated treatment center for beta thalassemia

Microscopic view of thalassemia

ZYNTEGLO® (betibeglogene autotemcel) is an FDA-approved gene therapy for transfusion-dependent beta thalassemia, which is an inherited blood disorder that causes the body to make less hemoglobin, resulting in anemia.

Children’s National Hospital is a designated qualified treatment center for Beta Thalassemia Gene Therapy. ZYNTEGLO® (betibeglogene autotemcel) is an FDA-approved gene therapy for transfusion-dependent beta thalassemia, which is an inherited blood disorder that causes the body to make less hemoglobin, resulting in anemia.

This unique therapy is made specifically for each child or adult, by adding functional copies of the beta-globin gene to their own blood stem cells. Most patients with beta thalassemia who have received a one-time ZYNTEGLO® treatment have been able to produce sufficient hemoglobin because of the treatment, freeing them from regular blood transfusions.

Evelio Perez, M.D., and Robert Nickel, M.D., lead the gene therapy program and discuss the importance of offering this gene therapy to patients with beta thalassemia.

Q: What has been the hold-up in this field and how does this work move the field forward?

A: Stem cell transplant using a donor’s cells (called allogeneic transplant) has been a curative treatment option for patients with beta thalassemia for many years. Unfortunately, many patients do not have a suitable donor. And, even for patients who have a donor, allogenic transplants have serious risks including a problem called graft versus host disease (GVHD) in which the new donor cells attack the patient’s body. Gene therapy like ZYNTEGLO® has no risk of GVHD because we use the patient’s own cells.

Q: How will this benefit patients? What excites you most about this advancement?

A: This treatment will give almost every patient with beta thalassemia the option of undergoing curative therapy. This is obviously exciting for patients because it means they no longer need to come to the hospital every 3-4 weeks for transfusions as well as take medications to treat the dangerous accumulation of iron in their body. It is also good for the health system because it will allow donated blood to go to other patients in need.

Q: How is Children’s National leading in this space?

A: This therapy really requires a multi-disciplinary team including members of the transplant, hematology, apheresis, stem cell lab and others! At Children’s National we have the experts on these teams and experience working together. As one of the largest sickle cell disease centers in the country, we are participating in research to hopefully help bring gene therapy to patients with sickle cell disease in the near future too.

Abstract Happy 2022 New Year greeting card with light bulb

The best of 2022 from Innovation District

Abstract Happy 2022 New Year greeting card with light bulbA clinical trial testing a new drug to increase growth in children with short stature. The first ever high-intensity focused ultrasound procedure on a pediatric patient with neurofibromatosis. A low dose gene therapy vector that restores the ability of injured muscle fibers to repair. These were among the most popular articles we published on Innovation District in 2022. Read on for our full top 10 list.

1. Vosoritide shows promise for children with certain genetic growth disorders

Preliminary results from a phase II clinical trial at Children’s National Hospital showed that a new drug, vosoritide, can increase growth in children with certain growth disorders. This was the first clinical trial in the world testing vosoritide in children with certain genetic causes of short stature.
(2 min. read)

2. Children’s National uses HIFU to perform first ever non-invasive brain tumor procedure

Children’s National Hospital successfully performed the first ever high-intensity focused ultrasound (HIFU) non-invasive procedure on a pediatric patient with neurofibromatosis. This was the youngest patient to undergo HIFU treatment in the world.
(3 min. read)

3. Gene therapy offers potential long-term treatment for limb-girdle muscular dystrophy 2B

Using a single injection of a low dose gene therapy vector, researchers at Children’s National restored the ability of injured muscle fibers to repair in a way that reduced muscle degeneration and enhanced the functioning of the diseased muscle.
(3 min. read)

4. Catherine Bollard, M.D., M.B.Ch.B., selected to lead global Cancer Grand Challenges team

A world-class team of researchers co-led by Catherine Bollard, M.D., M.B.Ch.B., director of the Center for Cancer and Immunology Research at Children’s National, was selected to receive a $25m Cancer Grand Challenges award to tackle solid tumors in children.
(4 min. read)

5. New telehealth command center redefines hospital care

Children’s National opened a new telehealth command center that uses cutting-edge technology to keep continuous watch over children with critical heart disease. The center offers improved collaborative communication to better help predict and prevent major events, like cardiac arrest.
(2 min. read)

6. Monika Goyal, M.D., recognized as the first endowed chair of Women in Science and Health

Children’s National named Monika Goyal, M.D., M.S.C.E., associate chief of Emergency Medicine, as the first endowed chair of Women in Science and Health (WISH) for her outstanding contributions in biomedical research.
(2 min. read)

7. Brain tumor team performs first ever LIFU procedure on pediatric DIPG patient

A team at Children’s National performed the first treatment with sonodynamic therapy utilizing low intensity focused ultrasound (LIFU) and 5-aminolevulinic acid (5-ALA) medication on a pediatric patient. The treatment was done noninvasively through an intact skull.
(3 min. read)

8. COVID-19’s impact on pregnant women and their babies

In an editorial, Roberta L. DeBiasi, M.D., M.S., provided a comprehensive review of what is known about the harmful effects of SARS-CoV-2 infection in pregnant women themselves, the effects on their newborns, the negative impact on the placenta and what still is unknown amid the rapidly evolving field.
(2 min. read)

9. Staged surgical hybrid strategy changes outcome for baby born with HLHS

Doctors at Children’s National used a staged, hybrid cardiac surgical strategy to care for a patient who was born with hypoplastic left heart syndrome (HLHS) at 28-weeks-old. Hybrid heart procedures blend traditional surgery and a minimally invasive interventional, or catheter-based, procedure.
(4 min. read)

10. 2022: Pediatric colorectal and pelvic reconstructive surgery today

In a review article in Seminars in Pediatric Surgery, Marc Levitt, M.D., chief of the Division of Colorectal and Pelvic Reconstruction at Children’s National, discussed the history of pediatric colorectal and pelvic reconstructive surgery and described the key advances that have improved patients’ lives.
(11 min. read)

Microscopic visual of a diseased muscle section

Gene therapy offers potential long-term treatment for limb-girdle muscular dystrophy 2B

Microscopic visual of a diseased muscle section

Microscopic visual of a diseased muscle section. Credit: Daniel Bittel.

Children’s National Hospital experts developed a new pre-clinical gene therapy for a rare disorder, known as limb-girdle muscular dystrophy (LGMD) 2B, that addresses the primary cellular deficit associated with this disease. Using a single injection of a low dose gene therapy vector, researchers restored the ability of injured muscle fibers to repair in a way that reduced muscle degeneration and enhanced the functioning of the diseased muscle. The treatment was safe, attenuated fibro-fatty muscle degeneration, and restored myofiber size and muscle strength, according to the study published in the Journal of Clinical Investigation.

With an incidence of less than 1 in 100,000, LGMD2B is a rare disorder caused by a genetic mutation in a large gene called dysferlin. This faulty gene leads to muscle weakness in the arms, legs, shoulder and pelvic girdle. Affected children and adults face trouble walking, climbing stairs and getting out of chairs. Individuals typically lose the ability to walk within years after the onset of symptoms, and often need assistance with everyday tasks such as showering, dressing and transferring.

This study described a new approach that avoids the need for packaging a large gene, like dysferlin, or giving a large vector dose to target the muscles, which are bottlenecks faced in ongoing gene therapy efforts aimed at muscular dystrophies.

“Currently, patients with LGMD2B have no gene or drug-based therapies available to them, and we are amongst the few centers developing therapeutic approaches for this disease,” said Jyoti K. Jaiswal, M.Sc. Ph.D., senior investigator of the Center for Genetic Medicine Research at Children’s National. “We are working to further enhance the efficacy of this approach and perform a longer-term safety and efficacy study to enable the clinical translation of this therapy.”

The genetic defect in dysferlin that is associated with LGMD2B causes the encoded protein to be truncated or degraded. This hinders the muscle fiber’s ability to heal, which is required for healthy muscles. In recessive genetic disorders, like LGMD2B, common pre-clinical gene therapy approaches usually target the mutated gene in the muscle, making them capable of producing the missing proteins.

“The large size of the gene mutated in this disease, and impediments in body-wide delivery of gene therapy vectors to reach all the muscles, pose significant challenges for developing gene therapies to treat this disease,” said Jaiswal.

To overcome these challenges, the researchers found another way to slow down the disease’s progression. The authors built upon their previous discovery that acid sphingomyelinase (hASM) protein is required to repair injured muscle cells. In this current work, the research team administered a single in vivo dose of an Adeno-associated virus (AAV) vector that produces a secreted version of hASM in the liver, which then was delivered to the muscles via blood circulation at a level determined to be efficacious in repairing LGMD2B patient’s injured muscle cells.

“Increased muscle degeneration necessitates greater muscle regeneration, and we found that improved repair of dysferlin-deficient myofibers by hASM-AAV reduces the need for regeneration, causing a 2-fold decrease in the number of regenerated myofibers,” said Daniel Bittel, D.P.T., PhD., research postdoctoral fellow of the Center for Genetic Medicine Research at Children’s National and a lead author of this study.

Sreetama Sen Chandra, Ph.D., who was a research postdoctoral fellow at Children’s National at the time of this study and served as co-lead author, also added that “these findings are also of interest to patients with Niemann-Pick disease type A since the pre-clinical model for this disease also manifests poor sarcolemma repair.”

Children’s National researchers of the Center for Genetic Medicine Research and the Rare Disease Institute (RDI) are constantly pursuing high-impact opportunities in pediatric genomic and precision medicine. Both centers combine its strengths with public and private partners, including industry, universities, federal agencies, start-up companies and academic medical centers. They also serve as an international referral site for rare disorders.

Gene therapy Schematic

Gene therapy Schematic. Credit: Daniel Bittel.

Dr. Catherine Bollard is accompanied by her mentees

Catherine Bollard, M.D., awarded two notable recognitions

Dr. Catherine Bollard is accompanied by her mentees

Dr. Catherine Bollard and some of her mentees.

For her work on developing cell-based therapies and dedication to her trainees, Catherine Bollard, M.D., MBChB, director of the Center for Cancer and Immunology Research at Children’s National hospital, receives two outstanding awards in her field.

Celebrating the minds behind the architecture of modern medicine and influencing the drug industry, The Medicine Maker, through an international panel of judges, added Dr. Bollard to the 2021 Power List in the category of advanced medicine.

Dr. Bollard mentioned that it is encouraging to see mRNA vaccine technology successfully fighting the COVID-19 pandemic because it paves the way for cancer vaccine advancements. Still, there are challenges affecting drug development. The centralized manufacturing hinders the large-scale production of patient-specific products as more cell therapies are getting approval, she added.

“Looking to the future, cell-based therapies will not be sustainable with a purely patient-specific centralized manufacturing model and, therefore, the field must move into the development of off-the-shelf cell therapies,” said Dr. Bollard. “The success of off-the-shelf virus-specific T-cells is especially exciting because it has the potential to be the platform for other antigen-specific and CAR-T cell therapies.”

A global society of clinicians, researchers, regulators, technologists and industry partners, The International Society for Cell & Gene Therapy (ISCT), will bestow Dr. Bollard the 2021 ISCT Darwin J. Prockop Mentoring Award on May 26. Her ongoing commitment to mentorship has advanced the careers of many aspiring professionals that have worked alongside her. The ISCT Award Committee selected someone that can inspire the current and future growing workforce. Dr. Bollard is highly recognized across the industry for her leadership, passion and dedication to her mentees, and her extraordinary efforts to advance their skills, capabilities and opportunities.

Dr. Catherine Bollard is accompanied by her mentees

To Patrick Hanley, Ph.D., chief and director of the Cellular Therapy Program at Children’s National, Dr. Bollard is the most deserving mentor for this award. She has provided advice and guidance to over 93 individuals, including 22 junior faculty, 27 post-doctoral fellows and 12 graduate students. Dr. Bollard also acts as a mentor to other senior investigators at Children’s National, particularly those in the Bone Marrow Transplantation division.

“For the past 15 years, Cath has been a strong mentor, friend, advocate, and voice of reason for me and has been instrumental in my success, both at Baylor College of Medicine and now at Children’s National,” said Hanley. “With her support and mentorship, I have been fortunate to publish high impact papers, earn a number of awards and receive prestigious grants. Without her guidance this wouldn’t have been possible.”

Amy Hont, M.D., oncologist for the Center for Cancer and Immunology Research at Children’s National, mentioned that Dr. Bollard is endlessly dedicated to her mentees and staff. “Dr. Bollard has been incredibly supportive of my research career throughout my training and progression to faculty. I feel very fortunate that I have been able to benefit not only from her unparalleled knowledge and expertise, but also her career advice and resources.”

Dr. Bollard leads clinical and research efforts to fight cancer and other inflammatory diseases by strengthening the immune system using adoptive cell therapy. She is a former president of the International Society of Cellular Therapy, and the current president of the Foundation for the Accreditation for Cellular Therapy (FACT). As a distinguished hematologist, immunologist and immunotherapist, she is working to develop cell and gene therapies for patients with cancer, viral infections and immune mediated diseases. She is especially interested in bone marrow and cord blood transplantation and improving outcomes after such transplant by decreasing infectious complications and preventing relapse. Dr. Bollard also has a specific interest in targeting viral infections in immune-suppressed patient populations, including individuals living with the human immunodeficiency virus.

Billie Lou Short and Kurt Newman at Research and Education Week

Research and Education Week honors innovative science

Billie Lou Short and Kurt Newman at Research and Education Week

Billie Lou Short, M.D., received the Ninth Annual Mentorship Award in Clinical Science.

People joke that Billie Lou Short, M.D., chief of Children’s Division of Neonatology, invented extracorporeal membrane oxygenation, known as ECMO for short. While Dr. Short did not invent ECMO, under her leadership Children’s National was the first pediatric hospital to use it. And over decades Children’s staff have perfected its use to save the lives of tiny, vulnerable newborns by temporarily taking over for their struggling hearts and lungs. For two consecutive years, Children’s neonatal intensive care unit has been named the nation’s No. 1 for newborns by U.S. News & World Report. “Despite all of these accomplishments, Dr. Short’s best legacy is what she has done as a mentor to countless trainees, nurses and faculty she’s touched during their careers. She touches every type of clinical staff member who has come through our neonatal intensive care unit,” says An Massaro, M.D., director of residency research.

For these achievements, Dr. Short received the Ninth Annual Mentorship Award in Clinical Science.

Anna Penn, M.D., Ph.D., has provided new insights into the central role that the placental hormone allopregnanolone plays in orderly fetal brain development, and her research team has created novel experimental models that mimic some of the brain injuries often seen in very preterm babies – an essential step that informs future neuroprotective strategies. Dr. Penn, a clinical neonatologist and developmental neuroscientist, “has been a primary adviser for 40 mentees throughout their careers and embodies Children’s core values of Compassion, Commitment and Connection,” says Claire-Marie Vacher, Ph.D.

For these achievements, Dr. Penn was selected to receive the Ninth Annual Mentorship Award in Basic and Translational Science.

The mentorship awards for Drs. Short and Penn were among dozens of honors given in conjunction with “Frontiers in Innovation,” the Ninth Annual Research and Education Week (REW) at Children’s National. In addition to seven keynote lectures, more than 350 posters were submitted from researchers – from high-school students to full-time faculty – about basic and translational science, clinical research, community-based research, education, training and quality improvement; five poster presenters were showcased via Facebook Live events hosted by Children’s Hospital Foundation.

Two faculty members won twice: Vicki Freedenberg, Ph.D., APRN, for research about mindfulness-based stress reduction and Adeline (Wei Li) Koay, MBBS, MSc, for research related to HIV. So many women at every stage of their research careers took to the stage to accept honors that Naomi L.C. Luban, M.D., Vice Chair of Academic Affairs, quipped that “this day is power to women.”

Here are the 2019 REW award winners:

2019 Elda Y. Arce Teaching Scholars Award
Barbara Jantausch, M.D.
Lowell Frank, M.D.

Suzanne Feetham, Ph.D., FAA, Nursing Research Support Award
Vicki Freedenberg, Ph.D., APRN, for “Psychosocial and biological effects of mindfulness-based stress reduction intervention in adolescents with CHD/CIEDs: a randomized control trial”
Renee’ Roberts Turner for “Peak and nadir experiences of mid-level nurse leaders”

2019-2020 Global Health Initiative Exploration in Global Health Awards
Nathalie Quion, M.D., for “Latino youth and families need assessment,” conducted in Washington
Sonia Voleti for “Handheld ultrasound machine task shifting,” conducted in Micronesia
Tania Ahluwalia, M.D., for “Simulation curriculum for emergency medicine,” conducted in India
Yvonne Yui for “Designated resuscitation teams in NICUs,” conducted in Ghana
Xiaoyan Song, Ph.D., MBBS, MSc, “Prevention of hospital-onset infections in PICUs,” conducted in China

Ninth Annual Research and Education Week Poster Session Awards

Basic and Translational Science
Faculty: Adeline (Wei Li) Koay, MBBS, MSc, for “Differences in the gut microbiome of HIV-infected versus HIV-exposed, uninfected infants”
Faculty: Hayk Barseghyan, Ph.D., for “Composite de novo Armenian human genome assembly and haplotyping via optical mapping and ultra-long read sequencing”
Staff: Damon K. McCullough, BS, for “Brain slicer: 3D-printed tissue processing tool for pediatric neuroscience research”
Staff: Antonio R. Porras, Ph.D., for “Integrated deep-learning method for genetic syndrome screening using facial photographs”
Post docs/fellows/residents: Lung Lau, M.D., for “A novel, sprayable and bio-absorbable sealant for wound dressings”
Post docs/fellows/residents: Kelsey F. Sugrue, Ph.D., for “HECTD1 is required for growth of the myocardium secondary to placental insufficiency”
Graduate students: Erin R. Bonner, BA, for “Comprehensive mutation profiling of pediatric diffuse midline gliomas using liquid biopsy”
High school/undergraduate students: Ali Sarhan for “Parental somato-gonadal mosaic genetic variants are a source of recurrent risk for de novo disorders and parental health concerns: a systematic review of the literature and meta-analysis”

Clinical Research
Faculty: Amy Hont, M.D., for “Ex vivo expanded multi-tumor antigen specific T-cells for the treatment of solid tumors”
Faculty: Lauren McLaughlin, M.D., for “EBV/LMP-specific T-cells maintain remissions of T- and B-cell EBV lymphomas after allogeneic bone marrow transplantation”

Staff: Iman A. Abdikarim, BA, for “Timing of allergenic food introduction among African American and Caucasian children with food allergy in the FORWARD study”
Staff: Gelina M. Sani, BS, for “Quantifying hematopoietic stem cells towards in utero gene therapy for treatment of sickle cell disease in fetal cord blood”
Post docs/fellows/residents: Amy H. Jones, M.D., for “To trach or not trach: exploration of parental conflict, regret and impacts on quality of life in tracheostomy decision-making”
Graduate students: Alyssa Dewyer, BS, for “Telemedicine support of cardiac care in Northern Uganda: leveraging hand-held echocardiography and task-shifting”
Graduate students: Natalie Pudalov, BA, “Cortical thickness asymmetries in MRI-abnormal pediatric epilepsy patients: a potential metric for surgery outcome”
High school/undergraduate students: Kia Yoshinaga for “Time to rhythm detection during pediatric cardiac arrest in a pediatric emergency department”

Community-Based Research
Faculty: Adeline (Wei Li) Koay, MBBS, MSc, for “Recent trends in the prevention of mother-to-child transmission (PMTCT) of HIV in the Washington, D.C., metropolitan area”
Staff: Gia M. Badolato, MPH, for “STI screening in an urban ED based on chief complaint”
Post docs/fellows/residents: Christina P. Ho, M.D., for “Pediatric urinary tract infection resistance patterns in the Washington, D.C., metropolitan area”
Graduate students: Noushine Sadeghi, BS, “Racial/ethnic disparities in receipt of sexual health services among adolescent females”

Education, Training and Program Development
Faculty: Cara Lichtenstein, M.D., MPH, for “Using a community bus trip to increase knowledge of health disparities”
Staff: Iana Y. Clarence, MPH, for “TEACHing residents to address child poverty: an innovative multimodal curriculum”
Post docs/fellows/residents: Johanna Kaufman, M.D., for “Inpatient consultation in pediatrics: a learning tool to improve communication”
High school/undergraduate students: Brett E. Pearson for “Analysis of unanticipated problems in CNMC human subjects research studies and implications for process improvement”

Quality and Performance Improvement
Faculty: Vicki Freedenberg, Ph.D., APRN, for “Implementing a mindfulness-based stress reduction curriculum in a congenital heart disease program”
Staff: Caleb Griffith, MPH, for “Assessing the sustainability of point-of-care HIV screening of adolescents in pediatric emergency departments”
Post docs/fellows/residents: Rebecca S. Zee, M.D., Ph.D., for “Implementation of the Accelerated Care of Torsion (ACT) pathway: a quality improvement initiative for testicular torsion”
Graduate students: Alysia Wiener, BS, for “Latency period in image-guided needle bone biopsy in children: a single center experience”

View images from the REW2019 award ceremony.

Children’s National Chief of Allergy and Immunology helps move gene therapy forward

Catherine Bollard

Catherine Bollard, M.D., MBChB, Chief of the Division of Allergy and Immunology, recently shared her expertise on an FDA panel that unanimously expressed its support for a pediatric cancer T-cell therapy called CTL019.

On July 12, 2017, a U.S. Food and Drug Administration advisory committee unanimously expressed its support for CTL019 – a pediatric cancer T-cell therapy. If the FDA follows the advice from the 10-member Oncologic Drug Advisory Committee (ODAC) – which included Children’s National Health System’s Catherine Bollard, M.D., MBChB, Chief of the Division of Allergy and Immunology and Director of the Program for Cell Enhancement and Technologies for Immunotherapy – CTL019 will become the first gene therapy to hit the market.

“Many of these children with recurrent cancer are out of other options to treat their illness,” said Dr. Bollard. “We are encouraged by these findings and the potential for this therapy to improve outcomes and quality of life.”

CTL019 is a chimeric antigen receptor (CAR) T-cell therapy, comprised of genetically modified T cells that target CD19, an antigen expressed on the surface of B cells. Also known as tisagenlecleucel, the therapy targets a single type of cancer called acute lymphoblastic leukemia and was created by Novartis.

In clinical trials, CTL019 showed unparalleled effectiveness. Of the 68 patients who received the drug, 52 responded almost immediately, and their cancer disappeared within the first three months. Seventy-five percent of those patients remained cancer-free six months after treatment. The therapy has one main side effect: an immune reaction called cytokine release syndrome, which can be deadly, with extended spiking fevers and other symptoms.

However, because of CTL019’s high efficacy, FDA scientists asked the ODAC panel to focus on the therapy’s safety and manufacturing challenges rather than whether or not it works.

Several committee members, including Dr. Bollard, expressed apprehension about the T-cell subpopulations’ heterogeneity, which could affect safety and efficacy. Another issue for consideration by the ODAC panel was the long-term side effects of CTL019 and the possibility that the T-cell modification could go awry, causing secondary cancers in the future.

Despite these concerns, the committee concluded that the strong efficacy data and the near-term benefits of CAR-T therapy more than tipped the scales in favor of the therapy. ODAC members were also pleased with Novartis’ plan to minimize risk, which includes limiting CTL019 distribution to selected centers with CAR T-cell therapy experience, and extensive, long-term post-marketing surveillance plans.

The FDA is not required to follow the ODAC panel’s advice when making its final decision, but it often does so. A final decision by the FDA is anticipated by late September.

Read more about the story in the Philadelphia Inquirer, Medpage Today and Healio.com.

Mark Batshaw

Gene therapy’s slow rebirth

Mark Batshaw

A speech by outgoing American Pediatric Society President Mark L. Batshaw, M.D., explored the impact of a single clinical trial on the entire field.

Gene therapy – delivering genetic material into patients’ cells as a way to treat or cure their diseases – has immense promise to alleviate or end many lifelong and deadly conditions. This treatment has so much potential that it was a heavy focus of research and research dollars around the world in the 1980s and 1990s.

However, many of these efforts came to a screeching halt in 1999 when a teenaged patient named Jesse Gelsinger died in a gene therapy trial aimed at curing a disease called ornithine transcarbamylase deficiency, a urea cycle disorder. Gelsinger’s death triggered a number of investigations, halted gene therapy trials in the United States, and severely restricted financial support from federal, foundation and industry funders.

The tragedy also spurred Mark L. Batshaw, M.D., one of the clinical trial investigators and newly named Chief Academic Officer at Children’s National Health System, to turn in his resignation. The chief executive at the time declined to accept it, instead naming an outside panel to investigate Dr. Batshaw’s role in a study marred by conflicts of interest, delays in updating patient consent forms, lack of adherence to the study protocol and ineffective team leadership.

As Dr. Batshaw passed the gavel to the next president of the American Pediatric Society during the Pediatric Academic Societies’ annual meeting this spring, he told attendees of his Presidential Address that “not a day goes by that I don’t think of Jesse Gelsinger and his family and hope that the work our team has continued will honor him by eventually achieving success with gene therapy.” In an act of altruism, 18-year-old Jesse Gelsinger had joined the trial with the aim of helping other kids suffering from metabolic disorder.

Dr. Batshaw recognizes that his is an unusual choice, speaking about his “greatest professional failure” when predecessors have used their addresses to speak exclusively about scientific accomplishments.

“Because I was a principal, I think telling this story first of all says, hey look, this guy who is president of this organization, who has had a significant career, is willing to talk openly about a failure and how he dealt with it and how the field dealt with that failure,” Dr. Batshaw says. “Secondly, the field of gene therapy right now is starting to explode. It’s telling two different stories in an integrated way: One is of a great personal failure – and failure of an entire field. And the recovery from that, and what the future will be for a technology that holds great promise.”

More than 1,000 gene therapy trials are currently underway, 23 of them at Phase III, the pivotal stage that makes or breaks approval by the Food and Drug Administration (FDA). Dr. Batshaw estimates about a dozen of those are likely to demonstrate robust enough results to progress to a formal application for FDA approval. “After a period of virtually no growth in gene therapy trials from 2000 to 2013, there has been a marked upswing in the past two to three years,” he says.

Children’s National is a study site for one of those clinical trials, a Phase I/II adenoassociated virus (AAV)-mediated gene therapy for late-onset ornithine transcarbamylase (OTC) deficiency. Children with urea cycle disorders have enzyme deficiencies that leave them unable to adequately dispose of waste nitrogen. Often as newborns, they develop severely elevated ammonia in their brains leading to encephalopathy, an often fatal condition. The Phase I work will test escalating doses in three patients for safety. The Phase II work will explore whether the gene therapy improves outcomes like lowering ammonia levels and improving patients’ ability to convert ammonia to urea. (A precursor study in an experimental model was among the most impactful research papers published by Children’s National authors in 2016.)

“So, for both our group’s program – and viral-delivered gene therapy in general – there has been a rebirth after the disastrous outcome of the initial adenovirus trial in OTC deficiency,” Dr. Batshaw said in his prepared remarks. “This resurgence has likely been fueled by improved viral vectors, especially AAVs, and an improved economy and industry investment. The future of gene therapy is likely to be enhanced by new genetic therapy platforms including RNA interference as a means of vertically transmitted gene regulation and the CRISPR gene-editing technology. It will also be impacted by the results of the trials that will be completed in the next few years, especially those using AAV vectors in hemophilia A and B, spinal muscular atrophy and leukemia.”

Looking forward 10 years, Dr. Batshaw is hopeful that gene therapy will become part of the therapeutic tools routinely used to help patients who suffer from rare disease and cancer. Making that next leap forward will be powered by innovative research, including work by colleagues at Children’s National. Among the presenters at PAS2017, the world’s largest pediatric research meeting, were more than 100 Children’s presenters, speakers and moderators.

“It makes me very proud that there are so many clinicians who are also scientists who are not satisfied with simply doing things the way they have always been doing it but constantly questioning how can we do things better for our children?” Dr. Batshaw says. “Our whole focus at Children’s National is caring for children, and that means caring for them the very best way possible and not being satisfied with current therapy if it’s not curative.”