Author Interviews, Cost of Health Care, Genetic Research, Hematology, JAMA / 22.03.2021 Interview with: Patrick DeMartino MD Pediatric Hematology and Oncology Fellow Doernbecher Children's Hospital Oregon Health & Science University What is the background for this study? Response: Dozens of gene therapies are expected to be on the market within a decade or so. Much has been written about the high prices of the therapies currently on the market (exceeding $1 million). However, only a small number of patients are eligible for these existing therapies each year. Gene therapy for sickle cell disease (SCD) appears promising and would potentially apply to a relatively large number of individuals in the U.S. We sought to explore potential affordability challenges associated with a gene therapy for SCD. (more…)
Author Interviews / 01.12.2020 Interview with: Daniel Maloney, Ph.D Farrar Lab Smurfit Institute of Genetics Trinity College Dublin What is the background for this study? Would you briefly describe the condition of Dominant optic atrophy? Response: Dominant Optic Atrophy (DOA) is a progressive blinding disorder that affects roughly 1:10,000 to 1:30,000 people. It is primarily caused by mutations in the OPA1 gene, which plays a pivotal role in the maintenance of the mitochondrial network. There is currently no way to prevent or cure DOA. We sought to build upon previous work to test if OPA1 could be delivered as a potential gene therapy intervention.  (more…)
Author Interviews, Diabetes, Heart Disease, UCSD / 28.03.2019 Interview with: H. Kirk Hammond, MD Professor of Medicine at University of California San Diego Basic research scientist and cardiologist San Diego Veterans' Affairs Healthcare System Dr. Hammond is winner of the 2017 William S. Middleton Award – the highest research honor in the U.S. Department of Veterans Affairs What is the background for this study? What are the main findings? Response: Worldwide, 9% of adults have diabetes, predominantly due to insulin resistance, known as Type 2 diabetes. It is associated with obesity and diets high in fat and carbohydrates. In this gene transfer study we showed that a single injection of a vector encoding a natural hormone (urocortin 2, Ucn2) increased glucose disposal and improved heart function in a model of diet-induced Type 2 diabetes in mice.  (more…)
Author Interviews, Cancer Research, Leukemia, Nature, University of Pennsylvania / 01.06.2018 Interview with: Dr. J Joseph Melenhorst, PhD Director, Product Development & Correlative Sciences laboratories (PDCS) Adjunct Associate Professor Penn Medicine Center for Cellular Immunotherapies University of Pennsylvania What is the background for this study? Would you briefly explain what is meant by CLL and CAR T cells?  Response: We started treating patients with a form of blood cancer called CLL (chronic lymphocytic leukemia) using a form of gene therapy wherein we engineer the patient’s own immune cells – T cells – with a tumor targeting molecule: The CAR, which stands for chimeric antigen receptor. When we engineer the patient’s immune cells we use a vehicle, in this case virus, that inserts the payload – the CAR – into the patient’s DNA. The virus disappears, and the CAR stays. Where this CAR inserts itself is unpredictable, but we always get stably engineered cells.  (more…)
Author Interviews, FDA, Genetic Research, Ophthalmology / 15.01.2018 Interview with: Dr. Stephen Rose PhD Chief Research Officer Foundation Fighting Blindness (FFB) Dr. Rose comments on the announcement of the FDA approval of voretigene neparvovec (LUXTURNA™) gene therapy for inherited blindness due to mutations in the RPE65 gene. What is the background for this announcement? What were the main findings from the study? Response: While it has been 30 years since the RPE65 gene was identified as causing Leber’s Congenital Amaurosis, this shows that it is possible to have an effective gene therapy for an inherited disease. As the first gene therapy for the eye or for an inherited disease, LUXTURNA is a historic milestone in the search for cures for all inherited retinal diseases (IRDs). As a one-time gene therapy, LUXTURNA will not only be life-changing for patients with vision loss due to mutations in the RPE65 gene, it also provides critical momentum for gene therapies - for the eye and other diseases - now in the clinic.  (more…)
Annals Internal Medicine, Author Interviews, Diabetes, Genetic Research, University of Pittsburgh / 07.01.2018 Interview with: Xiangwei Xiao, M.D., Ph.D. Assistant Professor of Department of Surgery, Children’s Hospital of Pittsburgh University of Pittsburgh School of Medicine, Pittsburgh, PA What is the background for this study? Response: Diabetes is a prevalent chronic disease characterized by persistently high blood glucose. Diabetes has two main subtypes, type 1 diabetes and type 2 diabetes. In type 1 diabetes, the immune system attacks and destroys insulin-producing beta cells in the pancreas, resulting in high blood levels of glucose. In type 2 diabetes, the beta cells do not produce enough insulin or the body is not able to use insulin effectively. (more…)
Author Interviews, Genetic Research, Ophthalmology / 07.11.2017 Interview with: Dr. Stephen M. Rose, PhD Chief Research Officer Foundation Fighting BlindnessDr. Stephen M. Rose, PhD Chief Research Officer Foundation Fighting Blindness Dr. Rose discusses the FDA advisory panel unanimously recommended approval of Spark Therapeutics' Gene Therapy Luxturna  for the treatment of patients with vision loss due to confirmed biallelic RPE65-mediated inherited retinal dystrophies, a group of rare blinding conditions caused by one of more than 220 different genes. Would you tell us a little about IRD? Whom does it affect and how?  How common is this disorder? Response: The retina at the back of the eye is responsible for collecting light and turning it into signals that are transmitted to the brain and interpreted as vision. Think of the retina as the film in a camera, or more recently the sensor at the back of a digital camera. Inherited rare retinal degenerations are when the retina at the back of the eye deteriorates and loses its ability to capture light, thereby leading to blindness. iRDs can affect anyone, no matter race or ethnicity. These are inherited conditions that are passed down from parents to children, if a parent or both parents are either affected already or are carriers for a variant in any of the over 250 genes responsible for retinal degeneration. There are over 15 different types of iRDs, with retinitis pigmentosa being the most common with a US affected population around 100,000. The rest of the iRDs make up another approximately 100,000 affected individuals in the US, so there are about 200,000 total affected individuals in the US. Worldwide these iRDs affect somewhere around one to two million individuals. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Genetic Research, Nature / 07.11.2017 Interview with: Dr Miguel Chillon PhD Department of Biochemistry and Molecular Biology Universitat Autonoma Barcelona Spain What is the background for this study? What are the main findings? Response: Klotho is a protein with an anti-aging and neuroprotective role. Recent studies show it prevents the development of cognitive problems associated with aging and Alzheimer's disease. Klotho works mainly by inhibiting the insulin / IGF-1 signaling pathway and decreasing the damage caused by oxidative stress in the brain. One of the latest results revealed that the concentration of Klotho in cerebrospinal fluid is significantly lower in Alzheimer's patients than in human controls of the same age; and it is lower in the elderly with respect to young adults. Our study used a gene therapy strategy to introduce the Klotho gene into the Central Nervous System of adult animals. With just a single injection of the Klotho gene, young adult animals were protected over time from the cognitive decline associated with aging in old animals. These exciting results pave the way to further advances in research and the development of a neuroprotective therapy based on Klotho. (more…)
Author Interviews, Genetic Research, Hearing Loss, Nature / 13.04.2017 Interview with: Lukas Landegger MD Molecular Neurotology Laboratory (PI Konstantina Stankovic) Massachusetts Eye and Ear Infirmary What is the background for this study? What are the main findings? Response: Genetic hearing loss affects more than 125 million people worldwide and constitutes a major hurdle for language acquisition and child development in general. Technological advances over the last decades, such as cochlear implants, have made it possible for deaf children to partially regain their sense of hearing. However, these devices still have several shortcomings, especially when listeners attempt to understand speech in noise or listen to music. In establishing Anc80L65 as a reliable vector for gene delivery in the inner ear and releasing the first data demonstrating convincing hearing and vestibular function rescue in mice, we provide a foundation for other researchers interested in assessing the benefits of gene therapy in animal models of human disease. (more…)
Author Interviews, Brigham & Women's - Harvard, Genetic Research, Hearing Loss, Nature / 09.02.2017 Interview with: Gwenaelle Geleoc, PhD Assistant Professor Department of Otolaryngology F.M. Kirby Neurobiology Center Children's Hospital and Harvard Medical School Boston, MA What is the background for this study? What are the main findings? Response: We seek to develop gene therapy to restore auditory and balance function in a mouse model of Usher syndrome. Usher syndrome is a rare genetic disorder which causes deafness, progressive blindness and in some cases balance deficits. We used a novel viral vector developed by Luk Vandenberghe and package gene sequences encoding for Ush1c and applied it to young mice suffering from Usher syndrome. These mice mimic a mutation found in patients of Acadian descent. We assessed recovery of hearing and balance function in young adult mice which had received the treatment. Otherwise deaf and dizzy, we found that the treated mice had recovered hearing down to soft sounds equivalent to a whisper and normal balance function. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, PNAS / 12.10.2016 Interview with: Dr. Magdalena Sastre PhD Faculty of Medicine, Department of Medicine Senior Lecturer Imperial College London What is the background for this study? Response: Alzheimer’s disease is the most common neurodegenerative disorder, affecting over 45 million people around the world. Currently, there are no therapies to cure or stop the progression of the disease. Here, we have developed a gene therapy approach whereby we delivered a factor called PGC-1α, which regulates the expression of genes involved in metabolism, inflammation and oxidative stress in the brain of transgenic mice. This factor is also involved in the regulation of energy in the cells, because it controls the genesis of mitochondria and in the generation of amyloid-β, the main component of the neuritic plaques present in the brains of Alzheimer’s disease patients. We have found that the animals with Alzheimer’s pathology treated with PGC-1α develop less amyloid plaques in the brain, perform memory tasks as well as healthy mice and do not have neuronal loss in the brain areas affected by the disease. (more…)
Author Interviews, Genetic Research, Neurological Disorders / 26.08.2016 Interview with: Lee Henderson, Ph.D. CEO Vybion, Inc. Ithaca, NY 14852Lee Henderson, Ph.D. CEO, Vybion, Inc. Ithaca, NY 14852 What is the background for this study? What are the main findings? Response: Huntington’s disease (HD) is a progressive and fatal neurodegenerative disease characterized by loss of both cognitive and motor function as a result of neuron loss primarily within the brain striatum. HD is directly caused by the expansion of CAG repeats in the huntingtin gene resulting in an expanded glutamine region (polyQ) near the N-terminus of the protein. Age of disease onset and the rate of progression is directly correlated to the size of the expansion with pathology observable at 35-70 repeats in adults and greater in juvenile onset. During normal turnover and degradation of the huntingtin protein, the N-terminal polyQ-containing fragments drive pathology and aggregate formation in cells. The direct link to progression has been described by several laboratories using cell-based and animal model studies and confirmed in humans as the binding of these N-terminal fragments to DNA and transcription factors that result in widespread gene dysregulation in neurons. (more…)
Author Interviews, Genetic Research, MD Anderson, Pain Research / 05.05.2016 Interview with: Hui-Lin Pan, MD, PhD Helen T. Hawkins Distinguished Professor and Deputy Division Head for Research Division of Anesthesiology and Critical Care, Unit 110 The University of Texas MD Anderson Cancer Center Houston, TX What is the background for this study? Dr. Hui-Lin Pan: Chronic nerve pain caused by damage to the peripheral nerve is a debilitating health problem and remains very difficult to treat. Sensory neurons in the spinal cord are normally inhibited by inhibitory neurotransmitters (GABA and glycine) to regulate transmission of painful information. A major feature of nerve injury-induced chronic pain is reduced spinal cord inhibition, resulting from diminished activity of a chloride transporter called KCC2. In this study, we investigated whether increasing KCC2 expression at the spinal level using a lentiviral vector can restore KCC2 activity, thereby reducing chronic nerve pain. (more…)
Author Interviews, Genetic Research, Ophthalmology / 18.01.2016

More on Gene Therapy on Interview with: Benjamin Bakondi, Ph.D. Postdoctoral Scientist Laboratory of: Shaomei Wang, M.D., Ph.D. Institute Director: Clive N. Svendsen, Ph.D. Board of Governors Regenerative Medicine Institute Cedars-Sinai Medical Center; Dept. of Biomedical Sciences Los Angeles, CA 90048 Medical Research: What is the background for this study? What are the main findings? Dr. Bakondi: Retinitis Pigmentosa (RP) is an inherited disease that causes progressive retinal degeneration and continual vision loss. Over 130 mutations have been identified in over 60 genes that cause RP. Gene replacement therapy is being evaluated for the recessive form of RP, in which both inherited alleles are dysfunctional. Retinitis Pigmentosa arising from dominant mutations however, would not benefit from such a strategy, and alternative options have not demonstrated clear efficacy. The idea for a therapeutic based on our approach is to use CRISPR/Cas9 to ablate the mutant copy of an allele and leave the wild-type copy unaffected. Barring haploinsufficiency, the wild-type allele should restore function and prevent retinal degeneration at levels commensurate with Cas9 cleavage efficiency. Our experimental findings provide proof-of-principle that a single DNA nucleotide difference in the genomic sequence between mutant and wild-type genes is enough to distinguish the mutant transcript for Cas9 cleavage with high fidelity. Eliminating production of the mutant rhodopsin protein prevented retinal degeneration and preserved vision. While Cas9/gRNA delivery improvement is underway, it should be noted that translational applicability of this approach is restricted to dominant mutations, not all of which may be targetable for ablation therapy. (more…)
Author Interviews, Endocrinology, Genetic Research, Weight Research / 22.10.2015

Urszula T. Iwaniec, Ph.D. Associate Professor Skeletal Biology Laboratory School of Biological and Population Health Sciences Oregon State University Corvallis, OR Interview with: Urszula T. Iwaniec, Ph.D. Associate Professor Skeletal Biology Laboratory School of Biological and Population Health Sciences Oregon State University Corvallis, OR 97331 Medical Research: What is the background for this study? What are the main findings? Dr. Iwaniec: Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related bone loss.  Leptin, a hormone produced by fat cells plays an essential role in weight regulation. Delivery of leptin directly into the hypothalamus by gene therapy normalizes body weight. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature female rats and determined the impact of leptin-induced weight loss on bone. Our findings show that hypothalamic leptin gene therapy reduced body weight with minimal effects on bone mass or microarchitecture. (more…)