Deep Dive on Gene Replacement Therapy

What is Gene Replacement Therapy

The following video provides an overview of gene replacement therapy and its potential use as a treatment for certain types of diseases

Dr. Diana Bharucha-Goebel

Director of the Muscular Dystrophy Association Care Center and Assistant Professor in the Division of Neurology at Children’s National Medical Center in Washington, D.C.

Presented By:

Dr. Diana Bharucha-Goebel

Director of the Muscular Dystrophy Association Care Center and Assistant Professor in the Division of Neurology at Children’s National Medical Center in Washington, D.C.

Dr. Diana Bharucha-Goebel is Director of the Muscular Dystrophy Association Care Center and Assistant Professor in the Division of Neurology at Children’s National Medical Center in Washington, D.C., and the Division of Pediatrics and Neurology at the George Washington University School of Medicine & Health Sciences. Dr. Bharucha-Goebel completed her medical training in the Drexel University College of Medicine in 2007, followed by a General Pediatric Residency in 2009, a Child Neurology Residency in 2012, and a Neuromuscular Fellowship in 2013, all of which were at the Children’s Hospital of Philadelphia. Starting in 2013, she has conducted additional research at the National Institutes of Health (NIH) in Bethesda, Maryland. Her interests include translational research in congenital neuromuscular diseases, with a particular focus on the evaluation and identification of disease focused outcome measures in rare disease as it pertains to better understanding functional outcomes for clinical trial readiness. Her research focus is in the development of early clinical translational gene replacement studies, as well as in studying the immune consequences and responses following gene transfer. Dr. Bharucha-Goebel is certified with the American Board of Psychiatry and Neurology (ABPN) in Neurology with Special Qualification in Child Neurology.

Transcript

Welcome. My name is Dr. Diana Bharucha-Goebel and I am a pediatric neuromuscular neurologist in Washington DC. In this chapter, I’m going to give you an overview of gene replacement therapy, a type of gene therapy particularly well suited for the treatment of monogenic diseases. There are five strategies used in gene therapy. These include gene addition, which involves introducing a new gene to aid and treatment. Gene inhibition, which involves deactivating a mutated gene that is not functioning properly. Gene replacement, which involves compensation of a mutated gene by adding a modified non-mutated version. Gene editing, which involves editing of a gene to introduce targeted changes. And genetic modulation of immune cells, in which the body’s own immune cells are engineered to attack disease cells.

This section will focus on gene replacement therapy. Monogenic diseases are caused by mutations within a single gene, making patients with these diseases good candidates for gene replacement therapy. As shown here, a mutation in a gene prevents normal production of the protein and leads to disease. Gene replacement therapy introduces a complementary DNA construct or modified gene that expresses a functional protein that is absent, reduced or nonfunctional due to a mutated gene in an effort to correct the disease. Gene replacement therapies make up the majority of the most advanced clinical gene therapy trials due to their conceptually simple design. They are being extensively studied for the treatment of monogenic diseases with a high degree of clinical success.

To date, a number of gene replacement therapies have already been approved and are being marketed for different indications such as severe combined immune deficiency due to adenosine deaminase deficiency, retinal dystrophy, spinal muscular atrophy, and beta thalassemia. Gene replacement therapy has also been explored in other monogenic diseases, some of which include blood disorders such as sickle cell anemia and hemophilia, retinal diseases such as RPE 65 associated Leber congenital amaurosis, Stargardt’s disease, Choroideremia, and RLBP1 retinitis pigmentosa, and neurodegenerative and neurological diseases such as Duchenne muscular dystrophy, Batten disease, Canavan disease, Rett syndrome, and spinal muscular atrophy.

In summary, gene replacement therapy is a type of gene therapy that introduces a CDNA construct or modified gene that expresses a functional protein that is absent, reduced or non-functional due to a mutated gene. It is particularly well suited for the treatment of monogenic diseases. Gene replacement therapy is currently approved for a number of different indications, which are detailed next and clinical trials of gene replacement therapies are ongoing in several fields of medicine. In this section, we will show potential disease targets for gene replacement therapy, important events and milestones that have led to its successful clinical applications, how this therapy is delivered and its design and main components.

Thank you for joining me to learn more about gene replacement therapy. We hope you continue to explore the gene therapy network.

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