Dirloctogene samoparvovec

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Dirloctogene samoparvovec, also known as SPK-8011, is an experimental gene therapy developed for hemophilia A by Roche and Spark Therapeutics. [1] [2] [3] [4] [5] [6]

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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.

<span class="mw-page-title-main">Haemophilia</span> Genetic disease involving blood clotting

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 a decreased level of consciousness.

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<span class="mw-page-title-main">Haemophilia B</span> Genetic X-linked recessive bleeding disorder

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.

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<span class="mw-page-title-main">Factor VIII</span> Blood-clotting protein

Factor VIII (FVIII) is an essential blood-clotting protein, also known as anti-hemophilic factor (AHF). In humans, factor VIII is encoded by the F8 gene. Defects in this gene result in hemophilia A, an X-linked coagulation disorder. Factor VIII is produced in the liver’s sinusoidal cells and endothelial cells outside the liver throughout the body. This protein circulates in the bloodstream in an inactive form, bound to another molecule called von Willebrand factor, until an injury that damages blood vessels occurs. In response to injury, coagulation factor VIII is activated and separates from von Willebrand factor. The active protein interacts with another coagulation factor called factor IX. This interaction sets off a chain of additional chemical reactions that form a blood clot.

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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. Her career has focused on pioneering work in the area of gene therapy, with many accomplishments in basic, translational, and clinical investigation in gene therapy.

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Spark Therapeutics, Inc. is a developer of gene therapy treatments, which treat debilitating genetic diseases. It is a subsidiary of Hoffmann-La Roche.

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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.

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Stephan A. Mayer is an American neurologist and critical care physician who currently serves as Director of Neurocritical Care and Emergency Neurology Services for the Westchester Medical Center Health System. Mayer is most noted for his research in subarachnoid and intracerebral hemorrhage, acute ischemic stroke, cardiac arrest, coma, status epilepticus, brain multimodality monitoring, therapeutic temperature modulation, and outcomes after severe brain injury. He has gained media attention for popularizing the concept that physicians have historically underestimated the brain’s resilience and capacity for recovery. He has authored over 400 original research publications, 200 chapters and review articles, and 370 abstracts.

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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.

Fidanacogene elaparvovec, sold under the brand name Beqvez, is a gene therapy delivered via adeno-associated virus used for the treatment of Hemophilia B.

References

  1. "Roche loses spark for gene therapy, axing hemophilia A candidate from pipeline" . Retrieved 8 December 2023.
  2. 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.
  3. 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 .
  4. 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 .
  5. 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.
  6. 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 .