Page 14 - HFA Dateline 2022 Special Edition
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However, he said, “We don’t really   “Gene therapy has the potential to
        know yet whether we can call it a
        cure.” Clark said he expects that    make a huge difference.” However,
        some gene therapies now in clinical
        trials may get regulatory approval   “we don’t really know yet whether
        and be licensed within the next      we can call it a cure.”
        couple of years. Currently, about
        30 companies are working on          —David Clark, PhD
        hemophilia gene therapy.

        A New Standard of Care?              of corrective blood clotting with an   The idea of injecting a virus into
        To understand gene therapy’s         injection weekly, or every two to four   your body may sound scary. But
        potential in changing treatment for   weeks, Pipe said.                    adeno-associated viruses can’t make
        people with bleeding disorders, it’s                                       you sick. “They’re not active viruses
        important to understand the current   “What we’ve observed for patients    anymore, and they don’t have any
        standard of care. Today, prophylactic   is that this has introduced a lot more   genes that can make them active
        therapy is the primary treatment to   spontaneity into their lives,” he said.   viruses,” Pipe said.
        prevent bleeds, including repeated   “They don’t have to think about their
        joint bleeds that can lead to        activities and their schedule linked to   AAV vectors are coated with a
        permanent joint damage.              their prophylactic dosing as much as   specific protein that encases the
                                             they did when they were on traditional   gene that produces FVIII or FIX (think
        “For decades, it has been factor     IV factor replacement. I think a lot   of the gene as being wrapped in a
        replacement therapy, and we have     of patients and families have really   package). Once the AAV particles
        well-established treatments that afford   enjoyed that spontaneity. But what   reach the liver, the protein coat
        protection from bleeds,” said Steven   we haven’t been able to achieve with   interacts with certain receptors on the
        Pipe, MD, medical director of the    any of these therapies is sustained full   surface of the liver. The receptors tell
        Pediatric Hemophilia and Coagulation   restoration of blood coagulation.”  the liver to accept the AAV, allowing
        Disorders Program and medical                                              the genes to reach the nucleus inside
        director of the Special Coagulation   Gene therapy could change that,      each liver cell. Once there, liver cells
        Laboratory at the University of      according to Pipe. “What gene therapy   help the genes to express and begin
        Michigan in Ann Arbor. He noted that   offers is a single infusion that would   producing FVIII or FIX.
        improvements in the half-life (the time   provide long-term efficacy,” he said.
        it takes for a drug to leave your body)                                    “We put specific elements alongside
        of factor replacement therapies have   Gene Therapy Basics                 the FVIII and FIX gene so that it
        reduced the frequency of IV infusions   So how exactly does gene therapy   will only be expressed in the tissue
        for some people while still providing   help people with bleeding disorders?   that we want it to—in this case,
        needed protection. “But the burden   The gene therapies that are furthest   the liver,” Pipe said. “These liver-
        of frequency is still more than most   along in clinical trials use an adeno-  specific genetic elements are called
        patients would like,” he said.       associated virus (AAV) that targets   promoters and enhancers. That way,
                                             the liver. Depending on the drug type,   even if the gene did get into non-liver
        Since its approval by the U.S. Food   researchers package the gene that    cells, the gene would not express
        and Drug Administration (FDA),       makes FVIII or FIX into an AAV vector   because the ‘machinery’ in the cell
        emicizumab (Hemlibra)—the first      (a vector is a living organism that acts   would not recognize it.”
        non-factor replacement therapy       as a carrier). Then, they infuse the
        for people with hemophilia—has       altered AAV vector into the patient.   It’s important to note that gene
        changed prophy for some. With        These particles enter the liver, where   transfer, or gene therapy that delivers
        its long half-life and ability to be   the factor-making gene activates (a   a working gene to help the body
        delivered subcutaneously (under      process known as expression). The     produce FVIII or FIX, doesn’t affect
        the skin) instead of through an IV,   expressed gene tells the patient’s liver   how bleeding disorders may be passed
        patients can maintain a steady state   to begin producing FVIII or FIX.    to a person’s offspring. “Patients will

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