• 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

    Gene Therapy at Dana-Farber/Boston Children's

    Through clinical trials and research, Dana-Farber/Boston Children's is at the forefront of the gene therapy evolution. Since 2012, we have treated 17 patients from 11 countries on three different gene therapy protocols. Under the direction of David Williams, MD, Dana-Farber/Boston Children's is one of the global leaders in pediatric gene therapy clinical research. We are currently conducting gene therapy clinical trials for adrenoleukodystrophy, X-linked severe combined immunodeficiency, Wiskott-Aldrich syndrome, and chronic granulomatous disease (see details below).

    Gene therapy trials for children with other diseases, such as sickle cell disease, relapsed acute lymphoblastic leukemia, and various malignant and non-malignant blood disorders are also under development. If successful, these gene therapy trials could produce potential cures for these diseases.

    To learn more about the trials below, email our gene therapy program or call 1-617-919-7008.

    Relapsed Acute Lymphoblastic Leukemia (ALL) Clinical Trial

    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.

    A gene therapy clinical trial for relapsed B-cell ALL at Dana-Farber/Boston Children’s 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

    Adrenoleukodystrophy (ALD) Clinical Trial

    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.

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

    • 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

    X-linked Severe Combined Immunodeficiency (X-SCID) Clinical Trial

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

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

    • Have a definitive diagnosis of SCIDX1 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

    Wiskott-Aldrich Syndrome (WAS) Clinical Trial

    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) Clinical Trial

    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
  • Contact Us: Gene Therapy

    For more information or to refer a patient for a gene therapy clinical trial, contact us:
    Phone: 617-919-7008
    Email: gene.therapy@childrens.harvard.educallout bg
  • Advances in Gene Therapy: "Bubble Boy Syndrome"

    Dr. David Williams 

    An international study led by researchers at Dana-Farber/Boston Children's shows that a new type of gene therapy may help boys with a immune disorder commonly known as “bubble boy” disease.

  • 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 effective treatment for cancers, blood disorders, and other conditions.