• What Do We See as the “Cure” for Hunter Syndrome?

    The Hunter Syndrome community, and the leadership of Saving Case & Friends in particular, sees gene therapy as the most promising treatment to meet our two requirements of a “cure”: (1) a one-time or at least non-perpetuity treatment, (2) with the potential for (a) preventing somatic, cognitive, and behavioral symptoms of Hunter Syndrome in pre-symptomatic patients, and (b) stabilizing somatic, cognitive, and behavioral symptoms in patients who are already progressed in disease.

  • What is Gene Therapy?

    Gene therapy is a technique that involves the transfer of genetic material into a host (human/animal) to treat diseases that are caused by mutated genes that function improperly or missing genes within the body.  In gene replacement therapy, scientists first identify a gene that is strongly associated with the onset of disease or its progression. In the case of Hunter Syndrome, scientists have identified the IDS gene.
    Scientists then show that correcting its information content or replacing it with expression of a normal gene counterpart corrects the defect in cultured cells and improves the disease in animal models, and is not associated with adverse outcomes. This “preclinical” work is currently ongoing in animal models of Hunter Syndrome.
    Scientists and clinicians then develop strategies to replace the gene or provide its function by administering genetic material into the patient. The relevant genetic material or gene usually is engineered into a “gene cassette” and prepared for introduction into humans according to stringent guidelines for clinical use. The cassette can be delivered directly as DNA, or engineered into a disabled viral vector, packaged into a type of membrane vesicles (termed liposome) so it is efficiently taken up by the appropriate cells of the body or used to genetically modify cells for implantation into patients. Promising gene therapy research in Hunter Syndrome uses the AAV9 vector to delivery working copies of the IDS gene.

  • How Does Gene Therapy Work?

    Gene therapy introduces a normal copy of the gene to restore the function of the missing or mutated proteins within cells. Genes can’t be inserted into the cells themselves, so they have to have a carrier or what is referred to as a vector. Viruses are often used as vectors since they have the capability of taking over cells, so therefore it would be able to deliver a new gene to these same cells. Once the gene enters the cells, then they have a normal functioning gene to properly restore the missing protein. The therapy is generally introduced into the body’s cells either by IV or an injection and various locations on the body have been used.

  • Is Gene Therapy Being Used in Other Diseases Besides Hunter Syndrome?

    Gene therapy is currently only available through clinical trials in the United States, although its use has been approved for certain diseases in other countries.
    The first gene therapy to be licensed in Europe, called Glybera (alipogene tiparvovec), was approved in November 2012 and treats a rare metabolic disorder called lipoprotein lipase deficiency, in which individuals lack the ability to break down fatty acids in the blood, leading to inflammation of the pancreas that is painful and sometimes fatal.
    There are currently dozens of clinical trials underway or preparing to begin around the world for genetic conditions somewhat similar to Hunter Syndrome such as Giant Axonal Neuropathy (GAN), Tay-Sachs Disease, Batten Disease, Severe Combined Immunodeficiency (SCID), and Sanfilippo Syndrome types A and B (also known as MPS III A and B).

  • What is the Status of Gene Therapy Research in Hunter Syndrome?

    Research and preclinical studies have developed an IDS2 gene that is attached to an AAV serotype 9 vector and is being injected into mice models (mice that suffer from Hunter Syndrome). The preclinical research involves injecting mice models in cohorts of ages to test the ability to stabilize or reverse effects of the disease as it progresses. Behavioral testing and other monitoring is also occurring to evaluate the effectiveness of the treatment cognitively and somatically. Early results have shown complete prevention of disease progression in pre-symptomatic mice. Additional older cohorts are currently being tested.
    Prior to an IND submission to the FDA to begin a clinical trial, a GLP toxicology study must also be conducted to determine the bio-distribution and toxicity levels of the treatment. In vivo toxicology studies are intended to assess the onset, severity, and duration of toxic effects, their dose dependency and degree of reversibility (or irreversibility). Such studies, including manufacturing of the vector to test, can cost close to half a million dollars.
    After completion of a GLP toxicology study, researchers design and prepare to begin a Phase I or Phase I/II clinical trial in humans. Manufacture of the vector for such a trial, as well as administration of the trial, can cost several million dollars.
    Researchers often seek government funding such as NIH grants for some of these costs, but private donations, nonprofit funding, and/or licensing of the research are usually required to bring it to clinical trials.

  • What Other Treatments are Currently Available for Hunter Syndrome and Why is Gene Therapy Seen as Superior?

    FDA-Approved Treatments

    • Elaprase (idursulfase): Enzyme replacement therapy approved by U.S. FDA in 2006 for the treatment of somatic effects of Hunter Syndrome. Does not cross the blood-brain-barrier in significant quantities and thus, does not prevent progressive brain damage that occurs in most patients. Requires a weekly 4-hour infusion and carries the risk of reactions, including life-threatening anaphylaxis, as well as antibody formation that can prevent full benefit from the treatment.

    Investigational Treatments

    • Hunterase (idursulfase beta): Enzyme replacement therapy currently approved in South Korea for the treatment of somatic effects of Hunter Syndrome. Similar profile, benefits, risks, and burdens as idursulfase. A clinical trial is expected to begin soon in the U.S.
    • Idursulfase IT: Enzyme replacement therapy administered intrathecally (into the spinal fluid) with the goal of preventing or slowing the progressive brain damage of Hunter Syndrome. Requires a monthly infusion via lumbar puncture (under general anesthesia) or via an intrathecal port-a-cath. Similar profile, benefits, risks, and burdens as idursulfase but with additional risks of intrathecal administration and activity. Has the potential for slowing, stabilizing, and/or improving cognitive regression. Currently in Phase II/III clinical trial in the U.S.
    • AGT-182: Enzyme replacement therapy via human insulin receptor monoclonal antibody-human Iduronate 2-Sulfatase (IDS) fusion protein. Requires a weekly infusion with similar risks and burdens as other enzyme replacement therapies. Currently in Phase I safety trial of adult patients in the U.S.
    • Bone Marrow / Cord Blood Transplant: Research has not established whether bone marrow or cord blood transplant can slow or prevent the progressive brain damage that occurs in most cases of Hunter Syndrome. Early research indicates that it does not, although it appears to slow or prevent somatic symptoms. Transplant also carries not insignificant morbidity and mortality risks.

    Comparison to Gene Therapy

    • Most of the above treatments have not been shown to prevent the progressive brain damage caused by Hunter Syndrome which, in most cases, causes the shortened life span of affected children.
    • All of the above treatments (with the exception of bone marrow / cord blood transplant) involve regular, ongoing treatments in perpetuity, the interruption of which would allow the continued progression of the disease both physically and mentally. Interruptions in treatment can occur because of personal or government funding, insurance, health, medical trauma, family circumstances, or disease progression.
    • All of the above treatments (with the exception of bone marrow / cord blood transplant) are forms of enzyme replacement therapy, which carry risks of life-threatening reactions and the development of antibodies over time, especially in children with more severe Hunter Syndrome mutations. In some cases, antibodies can prevent uptake of the therapy into cells, thus reducing the overall benefits of treatment.
    • In contrast, the goal of our gene therapy research is to develop a one-time treatment that will give the body its own perpetual ability to make the enzyme that it lacks.
  • How Can I Help?

    You can help by:

    1. Donating to help fund gene therapy research for Hunter Syndrome. All donations are tax deductible (Tax ID: 46-4617970). Saving Case & Friends, the sponsor of Project Alive, has no paid employees and little overhead. Our express goal is to fund this research.
    2. Sharing the Project Alive campaign with your friends and family. Please share the video at ProjectAlive.org as well as your personal support of our efforts.
    3. Sharing the Project Alive campaign on social media. Our goal is to fund this research and even with small donations, but a large audience, we can do that. Please help us share our children’s dream of simply wanting to be alive by using the hashtag #WhenIGrowUp, following our campaign on Saving Case & Friends on Facebook, Saving Case & Friends on Twitter, and Project Alive on Instagram, and sharing our posts.