Investigators in the Gene and Cell Therapy program work to improve current treatments, develop corrective therapies and explore new technologies to address genetic disease. A major focus of the research group is to examine the interaction between gene therapies and the immune system.
Using hemophilia as a model, the group seeks to create innovative approaches to induce immune tolerance to current treatments and correct the genetic malfunctions that lead to disease.
Learn more about active research in the Gene and Cell Therapy program.
Disease correctionThe Gene and Cell Therapy research group focuses on gene and cell therapies that use a recombinant adeno-associated virus, which transfers genetic material to the patient’s cells and enables the ongoing production of therapeutic proteins. Using this treatment in hemophilic models, the group has already accomplished near-complete and complete disease correction.
Immune toleranceCurrent treatments of certain genetic disorders can cause an immune response in some patients, making therapy ineffective. Investigators in the Gene and Cell Therapy program examine the interaction of gene therapies and the immune system to prevent rejection and induce tolerance to treatment. Currently, the group is exploring tolerance therapies such as oral therapies, cell-based immunotherapies, gene therapy and small molecule drugs.
Expertise in hemophiliaThe Gene and Cell Therapy group conducts its research in the context of hemophilia. Although hemophilia is treatable in approximately 70 percent of its patients in the developed world, it impacts people of all nations and has no known cure. In patients whose immune systems reject treatment, alternative options are not only scarce but also difficult, expensive and invasive, while offering no guarantee of effectiveness.
The goal of the Gene and Cell Therapy program is to discover innovative ways to permanently correct disease and induce tolerance to treatment for patients with hemophilia and other genetic disorders.
Answers to common questions about hemophilia and immune rejection.
Hemophilia is an X-linked genetic disorder that prevents the blood from clotting normally. People with hemophilia may experience excessive internal and external bleeding, which can be life-threatening.
Considered a rare disease, hemophilia affects approximately one in 5,000 male births worldwide. Hemophilia has no geographic or ethnic preference, but because it is an X-linked genetic disorder, the vast majority of people with hemophilia are male. Although females can have hemophilia, these instances are far fewer. More commonly, women are carriers of the disease.
In developed nations, hemophilia is most commonly treated with intravenous injections of replacement clotting factors. These injections may need to be administered up to three times a week, depending on the patient’s need.
In approximately one-third of patients treated for hemophilia, the immune system develops antibodies that reject the clotting factor proteins that have been introduced into the patient’s bloodstream. When a patient develops these antibodies, or inhibitors, the treatment is ineffective. Without effective treatment, internal and external bleeds can be life-threatening
Current immune tolerance induction methods are designed to reverse immune responses that have already been established. However, immune tolerance induction can be invasive, costly and difficult. Some patients are given a catheter for intravenous access and are administered high daily doses of proteins that support clotting. Although the mechanisms are not fully understood, tolerance is eventually induced by approximately 70 percent of these patients. Currently, there are no clinical protocols that prevent immune rejection.
Video Interview
View Kaczmarek's other interview on current hurdles in AAV-based gene therapy for hemophilia.