• Gene Therapy for Children

    What is gene therapy?

    gene therapy doctor and patientOur genes, which hold the code for all of our body's functions, are made of DNA. Damage to DNA, such as a mutation, is an underlying cause of the genetic defects that lead to cancers, blood disorders, and other conditions. Gene therapy delivers DNA into a patient’s cells to replace faulty or missing genes—or adds new genes—in an attempt to cure cancer or make changes so the body is better able to fight off disease.

    Scientists are investigating a number of different ways to do this:

    • Replacing missing or mutated genes, which is the most common approach
    • Changing the regulation of genes; mutated genes that cause cancer could be turned off so they don’t cause disease or turned on to fight disease.
    • Making cancer cells more recognizable to the body’s immune system to improve the body’s disease-fighting response, also known as immunotherapy.

    How does gene therapy deliver new genes into cells?

    With gene therapy, the DNA for a gene or genes is carried into a patient’s cells by a delivery vehicle called a vector, typically a specially engineered virus. The vector then inserts the gene(s) into the cells' DNA.

    What are the steps of gene therapy?

    For patients, the process for delivering genes to cells is relatively simple. See below, or view larger.

    gene therapy process

    Our Gene Therapy Clinical Trials

    Through clinical trials and research, Dana-Farber/Boston Children's is at the forefront of the gene therapy evolution. Since 2012, we have treated 25 patients from 11 countries through our gene therapy protocols. Launched by Dana-Farber/Children’s President David Williams, MD, and now under the direction of Alessandra Biffi, MD, the joint center is one of the global leaders in pediatric gene therapy clinical research. We are currently conducting the gene therapy clinical trials below. Gene therapy trials for children with other diseases are also under development.

    Learn about our gene therapy trials below, or email our gene therapy program or call 1-617-632-5064.

    X-linked Severe Combined Immunodeficiency (SCID-X1) – Recently Updated

    X-linked severe combined immunodeficiency (SCID-X) is a rare genetic immunodeficiency that prevents a child's bone marrow from producing infection-fighting white blood cells.

    Our gene therapy trial for SCID-X1 uses a self-inactivating (SIN) Gammaretroviral Vector. Based on experience in other transplant and gene therapy trials, we recently modified the protocol to include low dose Busulfan conditioning in patients without active infections, in order to enhance correction of humoral (B cell) immunity.

    As of October 2016, we have enrolled and treated 7 patients in the United States and 6 patients in Europe through this trial. An interim analysis of the study was published in the New England Journal of Medicine in October 2014. (Hacein-Bey-Abina S, Pai S-Y, Gaspar HB, et al. A Modified γ-Retrovirus Vector for X-Linked Severe Combined Immunodeficiency. N Engl J Med. 2014 Oct 9;371(15):1407–17.) There have been no serious adverse effects related to the gene therapy medicinal product to date in this trial.

    Children who meet the following criteria may be eligible to take part in this trial:

    • Have a definitive diagnosis of SCID-X1 and either
      • Lack an HLA-matched family donor and, if >3.5 months old, lack an HLA-identical (A,B,C,DR,DQ) unrelated donor
      • Be of any age with an active, therapy-resistant infection or other medical conditions that significantly increase the risk of allogeneic transplant

    Adrenoleukodystrophy (ALD)

    Note: This trial is ongoing, but is temporarily closed to accrual.

    Adrenoleukodystrophy (ALD) is a rare and progressive genetic disorder more often diagnosed in boys that affects the nervous system and the adrenal glands (small glands found on top of the kidneys). The cells of a child with ALD are missing the gene for an enzyme called ALDP, which helps break down fatty acids.

    Eligibility requirements for our gene therapy trial for children with ALD include:

    • Be male, aged 17 years or younger at time of consent
    • Have active cerebral ALD as defined by elevated VLCFA levels
    • Have active central nervous system (CNS) disease established by central radiographic review of brain MRI demonstrating:
      • Loes score between 0.5 and 9 (inclusive) on the 34-point scale
      • Gadolinium enhancement of demyelinating lesions on MRI
    • Lack availability of a 10/10 human leukocyte antigen (HLA)-matched sibling donor

    Wiskott-Aldrich Syndrome (WAS)

    Wiskott-Aldrich syndrome (WAS) is a rare genetic immunodeficiency that keeps a child's immune system from functioning properly. It also makes it difficult for a child's bone marrow to produce platelets, making a child prone to bleeding.

    Patients who meet the following criteria may be eligible to take part in Dana-Farber/Boston Children's gene therapy trial for children with WAS:

    • Be aged 3 months to 35 years
    • Have confirmed molecular diagnosis by DNA sequencing
    • Have severe disease indicated by absence of WAS protein by flow cytometry AND mutation predictive of severe disease (i.e. nonsense, frameshift or large deletion mutation)
    • Lack availability of HLA-genotypically identical sibling bone marrow donor
    • Have adequate organ function and performance status

    Patients under age 5 must also:

    • Lack a 9/10 or 10/10 molecularly HLA-matched unrelated donor after 3 months of searching
    • Lack a 6/6 molecularly HLA-matched cord blood donor of adequate cell number after 3 months of searching

    Chronic Granulomatous Disease (CGD)

    Chronic Granulomatous Disease (CDG) is a genetic disease that affects males. CGD patients have problems with some of the white blood cells, neutrophils. CGD patients generally have low numbers of white blood cells, and some of these white blood cells do not work right, leading to infections. CGD patients can have other problems with chronic inflammation of the bowel and swollen gums.

    Patients who meet the following criteria may be eligible to take part in Dana-Farber/Boston Children’s gene therapy trial for children with CGD:

    • Older than 23 months of age
    • Have a confirmed diagnosis of CGD by DNA sequencing
    • Do not have an 10/10 HLA matched bone marrow donor available
    • Have at least one prior or ongoing severe infection and/or inflammatory complication requiring hospitalization despite therapy
    • No co infection with HIV, Hepatitis B, Hepatitis C, CMV, Adenovirus or Parvovirus B 19

    Relapsed Acute Lymphoblastic Leukemia (ALL)

    Relapsed acute lymphoblastic leukemia, or relapsed ALL, refers to the return of acute lymphoblastic leukemia (ALL) in patients who have already undergone treatment for the disease. Between 15 and 20 percent of children who are treated for ALL and achieve an initial complete remission (CR) will have the disease return (relapse) at some point.

    This gene therapy clinical trial for relapsed B-cell ALL is testing the safety of giving patients immune-cancer-fighting cells that are created from their own blood; these are called "modified T-cells." The goal is to find a safe dose of modified T-cells for patients whose leukemia has returned.

    Children who meet the following criteria may be eligible to take part in this clinical trial:

    • Aged under 26 years
    • Have a history of relapsed/refractory CD19+ B-cell ALL involving the bone marrow
    • Patient would not benefit from additional chemotherapy as determined by the treating physician

    Patients also must NOT have the following:

    • Active HIV, hepatitis B or hepatitis C infection
    • Any concurrent active malignancies requiring any therapy other than expectant observation

    Hemophilia B

    Hemophilia B is an X-linked recessive genetic bleeding disorder caused by mutations in the factor IX (FIX) gene. FIX is produced in the liver and is critical for fibrin clot formation. Hemophilia B is characterized by frequent, spontaneous internal bleeding that can lead to chronic joint damage, intracranial hemorrhage, and even death. Current treatment for hemophilia B is based on replacement of the deficient FIX with IV injections of recombinant FIX protein prophylactically or as needed to treat bleeding episodes.

    Our gene therapy clinical trial for hemophilia B evaluates whether the AAV vector carrying a FIX gene can increase FIX levels in patients with moderate to severe hemophilia B. If you think you may be a candidate for one of these trials, please contact us and we can discuss the two options with you.

    Safety and Dose Finding Study of DTX101 (AAVrh10FIX) in Adults With Moderate/Severe to Severe Hemophilia B
    This study will evaluate the safety and efficacy of the adeno-associated virus (AAV) to deliver the human factor IX (hFIX) gene, the healthy gene necessary to make FIX, to the liver where FIX is normally produced. This study will determine if AAVrh10 can produce clinically meaningful FIX levels in patients with moderately/severe or severe hemophilia B.

    Eligibility criteria:

    • Male 18 years of age or older
    • Moderate/severe or severe hemophilia B (baseline FIX activity ≤2% of normal or documented history of FIX activity ≤2%)
    • At least 3 bleeding episodes per year that require on-demand treatment with FIX OR are treated with a prophylactic regimen of FIX
    • No documented history of inhibitors (neutralizing antibodies) to exogenous FIX
    • No known allergic reaction to exogenous FIX

    Blood Cell Disorders – Malignant and Non-malignant

    This gene therapy clinical trial will evaluate pediatric patients who have a malignant or non-malignant blood cell disorder – including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), non-Hodgkin lymphoma, myelodysplastic syndrome (MDS), or an immunologic deficiency syndrome – who are having a blood stem cell transplant depleted of T cell receptor (TCR) alfa and beta cells from a partially matched family donor. The study will assess whether immune cells, called T cells, from the family donor – which will be specially grown in the laboratory and given back to the patient along with the stem cell transplant – can help the immune system recover faster after transplant.

    Children who meet the following criteria may be eligible to take part in this trial:

    • Be between ages 3 Months and 21 Years
    • Have life-threatening hematological malignancy deemed eligible for allogeneic stem cell transplantation – OR – a non-malignant disorder that could be cured by an allograft
    • Lack availability of an HLA identical donor
    • Have a life expectancy greater than 10 weeks
    • Have Lansky/Karnofsky score > 50, WHO > 4
    • Must not be receiving immunosuppressive treatment for Graft versus Host Disease (GvHD)
    • Must not be experiencing significant liver dysfunction or severe cardiovascular disease

    Learn more about this gene therapy clinical trial.

  • Contact Us: Gene Therapy

    For more information or to refer a patient for a gene therapy clinical trial, contact us:
    Phone: 617-632-5064
    Email: gene.therapy@childrens.harvard.educallout bg
  • Advances in Gene Therapy

    Dr. David Williams

    Studies led by researchers at Dana-Farber/Boston Children's show the promise of gene therapy in treating an increasing number of pediatric diseases.

  • Concierge Services

    Our team provides extensive concierge services to help gene therapy patients and families with travel arrangements, housing, and more. Call us at (617) 919-7008 to learn more.
  • Video: Gene Therapy

    Sung-Yun Pai, MD, explains the basic process of gene therapy.

  • Stem Cell Transplant

    Dana-Farber/Boston Children’s has one of the largest and most experienced pediatric stem cell transplant programs in the U.S. Stem cell transplants can provide treatment for cancers, blood disorders, and other conditions.