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Gene therapy is a medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells.
Haemophilia, or hemophilia, is a mostly inherited genetic disorder that impairs the body's ability to make blood clots, a process needed to stop bleeding. This results in people bleeding for a longer time after an injury, easy bruising, and an increased risk of bleeding inside joints or the brain. Those with a mild case of the disease may have symptoms only after an accident or during surgery. Bleeding into a joint can result in permanent damage while bleeding in the brain can result in long term headaches, seizures, or an altered level of consciousness.
The retina is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then processes that image within the retina and sends nerve impulses along the optic nerve to the visual cortex to create visual perception. The retina serves a function which is in many ways analogous to that of the film or image sensor in a camera.
Haemophilia A is a blood clotting disorder caused by a genetic deficiency in clotting factor VIII, thereby resulting in significant susceptibility to bleeding, both internally and externally. This condition occurs almost exclusively in males born to carrier mothers due to X-linked recessive inheritance. Nevertheless, rare isolated cases do emerge from de novo (spontaneous) mutations.
Haemophilia B, also spelled hemophilia B, is a blood clotting disorder causing easy bruising and bleeding due to an inherited mutation of the gene for factor IX, and resulting in a deficiency of factor IX. It is less common than factor VIII deficiency.
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin.
Von Willebrand disease (VWD) is the most common hereditary blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of von Willebrand factor (VWF), a multimeric protein that is required for platelet adhesion. It is known to affect several breeds of dogs as well as humans. The three forms of VWD are hereditary, acquired, and pseudo or platelet type. The three types of hereditary VWD are VWD type 1, VWD type 2, and VWD type 3. Type 2 contains various subtypes. Platelet type VWD is also an inherited condition.
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also influence adaptive immune responses and exert tissue repair functions. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors.
Coagulation factor VIII is an essential blood clotting protein. In humans, it is encoded by F8 gene. Defects in this gene result in hemophilia A, an X-linked bleeding disorder.
Coagulation factor VII is a protein involved in coagulation and, in humans, is encoded by gene F7. It is an enzyme of the serine protease class. Once bound to tissue factor released from damaged tissues, it is converted to factor VIIa, which in turn activates factor IX and factor X.
Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus Dependoparvovirus, which in turn belongs to the family Parvoviridae. They are small replication-defective, nonenveloped viruses and have linear single-stranded DNA (ssDNA) genome of approximately 4.8 kilobases (kb).
Factor VIII is a medication used to treat and prevent bleeding in people with hemophilia A and other causes of low factor VIII. Certain preparations may also be used in those with von Willebrand's disease. It is given by slow injection into a vein.
Katherine A. High is an American doctor-scientist who is an emeritus professor at the Perelman School of Medicine at the University of Pennsylvania. She was the co-founder, president, and chief scientific officer of Spark Therapeutics and currently serves as President of Therapeutics at AskBio. She has worked in the area of gene therapy, performing both basic research and clinical investigations. She has been recognized for her distinguished contributions to the field, having designed, sponsored, and conducted the first clinical trial of an adeno-associated viral vector (AAV) gene therapy injected into the skeletal muscle (1999), the first trial of AAV gene therapy introduced into the liver (2001), and the first trial in the US of an AAV gene therapy injected into the subretinal space (2007).
Spark Therapeutics, Inc. is a developer of gene therapy treatments, which treat debilitating genetic diseases. It was founded in 2013 and has been a subsidiary of Hoffmann-La Roche since 2020.
Non-surgical fertility control is the prevention of reproduction without the use of surgery. The most common form of sterilization in dogs and cats is surgical, spaying in females and castration in males. Non-surgical fertility control can either result in sterilization or temporary contraception and could offer a cheaper way to keep wild dog and cat populations under control. As of 2019, only contraceptives are commercially available. Research is ongoing into methods that could result in permanent suppression of fertility.
Valoctocogene roxaparvovec, sold under the brand name Roctavian, is a gene therapy used for the treatment of hemophilia A. It was developed by BioMarin Pharmaceutical. Valoctocogene roxaparvovec is made of a virus (AAV5) that has been modified to contain the gene for factor VIII, which is lacking in people with hemophilia A. It is an adeno-associated virus vector-based gene therapy. It is given by intravenous infusion.
Adele Kay Fielding is a British physician-scientist who is a Professor of Haematology at University College London. Fielding was President of the British Society for Haematology from 2020 until 2022.
Marie Claire McLintock was a New Zealand haematologist and obstetric physician. She was an expert in medical conditions and disorders related to bleeding and blood clotting, and medical problems associated with pregnancy.
SPK-3006 is an experimental gene therapy developed for Pompe disease by Spark Therapeutics. It is delivered via adeno-associated virus and is intended to increase alpha-glucosidase production in the liver.
Fidanacogene elaparvovec, sold under the brand name Beqvez among others, is a gene therapy delivered via adeno-associated virus used for the treatment of hemophilia B.
References
- ↑ "Roche loses spark for gene therapy, axing hemophilia A candidate from pipeline" . Retrieved 8 December 2023.
- ↑ Mannucci, Pier Mannuccio (March 2023). "Hemophilia treatment innovation: 50 years of progress and more to come". Journal of Thrombosis and Haemostasis. 21 (3): 403–412. doi: 10.1016/j.jtha.2022.12.029 . PMID 36858789. S2CID 257276049.
- 1 2 Croteau, Stacy E.; Eyster, M. Elaine; Tran, Huyen; Ragni, Margaret V.; Samelson-Jones, Benjamin J.; George, Lindsey; Sullivan, Spencer; Rasko, John E.J.; Moormeier, Jill; Angchaisuksiri, Pantep; Teitel, Jerome; Kenet, Gili; Wynn, Tung; Jaworski, Kristen; Macdougall, Amy; Jaeger, Savina; Trivedi, Trupti; Mingozzi, Federico; Chang, Tiffany; Levy, Gallia (15 November 2022). "Long-Term Durable FVIII Expression with Improvements in Bleeding Rates Following AAV-Mediated FVIII Gene Transfer for Hemophilia A: Multiyear Follow-up on the Phase I/II Trial of SPK-8011". Blood. 140 (Supplement 1): 1899–1901. doi: 10.1182/blood-2022-158903 .
- ↑ Elkouby, Liron; Armour, Sean M.; Toso, Raffaella; DiPietro, Marti; Davidson, Robert J.; Nguyen, Giang N.; Willet, Mallory; Kutza, Stephanie; Silverberg, Joseph; Frick, Jennifer; Crosariol, Marco; Wang, Yuhuan; Wang, Chuansong; High, Katherine A.; Sabatino, Denise E.; Anguela, Xavier M. (March 2022). "Preclinical assessment of an optimized AAV-FVIII vector in mice and non-human primates for the treatment of hemophilia A". Molecular Therapy - Methods & Clinical Development. 24: 20–29. doi: 10.1016/j.omtm.2021.11.005 . PMC 8666598 . PMID 34977269.
- ↑ High, Katherine A.; George, Lindsey A.; Eyster, M. Elaine; Sullivan, Spencer K.; Ragni, Margaret V.; Croteau, Stacy E.; Samelson-Jones, Ben J.; Evans, Matthew; Joseney-Antoine, Marcelyne; Macdougall, Amy; Kadosh, Judith; Runoski, Alexa R.; Campbell-Baird, Cynthia; Douglas, Kayla; Tompkins, Summer; Hait, Howard; Couto, Linda B.; Bassiri, Ashlyn Eaton; Valentino, Leonard A.; Carr, Marcus E.; Hui, Daniel J; Wachtel, Katie; Takefman, Daniel; Mingozzi, Federico; Anguela, Xavier M.; Reape, Kathleen B (29 November 2018). "A Phase 1/2 Trial of Investigational Spk-8011 in Hemophilia a Demonstrates Durable Expression and Prevention of Bleeds". Blood. 132 (Supplement 1): 487. doi:10.1182/blood-2018-99-115495. S2CID 81439244.
- ↑ Evans, Matthew S.; Rybka, Witold B.; Croteau, Stacy E.; Tran, Huyen; Rasko, John E.J.; Jaworski, Kristen; MacDougall, Amy; Jaeger, Savina; Mingozzi, Federico; Chang, Tiffany; Levy, Gallia (15 November 2022). "The Effects of Immunomodulation with Corticosteroids to Manage an AAV Capsid Immune response in the Phase I/II Study of SPK-8011". Blood. 140 (Supplement 1): 10654–10655. doi: 10.1182/blood-2022-159017 .