Katherine A. High

Last updated
Katherine A. High
Born
High Point, North Carolina
NationalityAmerican
Alma mater Harvard College, University of North Carolina School of Medicine
Known forGene Therapy
Childrenthree, including Sarah Steele
Scientific career
Fields Hematology
Institutions University of Pennsylvania, Spark Therapeutics
Academic advisors Edward J. Benz Jr.

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. [1] 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.

Contents

Education

High received an A.B. in chemistry at Harvard University in 1972. [2] [3] She started her medical training at the University of North Carolina (UNC) School of Medicine, during which she took a leave of absence to work in a chemistry research lab at UNC. [4] After returning and completing her medical degree in 1978, High continued with a residency in internal medicine. [5] She then became a hematology fellow at Yale University under the supervision of Edward J Benz Jr, during which she worked on the molecular genetics of globin genes and oncogenes. [6] [5]

Career and research

High has been recognized for her distinguished contributions to the field of gene therapy, having designed, sponsored, and conducted the first clinical trial of an adeno-associated viral vector (AAV) gene therapy injected into the skeletal muscle (1999), [7] the first trial of AAV gene therapy introduced into the liver (2001), [8] and the first trial in the US of an AAV gene therapy injected into the subretinal space (2007). [9]

High was a faculty member at the University of North Carolina - Chapel Hill for seven years, [10] [5] where she started her career by developing a canine model of the study of gene therapy for hemophilia by cloning the canine Factor IX gene. [11] She also identified the mutations responsible for several Factor VII and Factor X-deficient blood clotting disorders. [12] High moved to the University of Pennsylvania and Children's Hospital of Philadelphia, where she began pioneering gene therapies for blood disorders. [13] During her career at the University of Pennsylvania, High expanded her research into gene therapy solutions for hereditary blindness together with Dr. Jean Bennett. [14]

She was the director of the Center for Cellular and Molecular Therapeutics, and as of 2001 head of hematology research, [1] at the Children's Hospital of Philadelphia and an investigator of the Howard Hughes Medical Institute. [15] [16] High is an elected member of the National Academy of Medicine of the American Academy of Arts and Sciences, and of the Faculty of Pharmaceutical Medicine of the Royal College of Physicians (London).

Along with Jean Bennett, in 2018, she was awarded Sanford Health's $1 million Lorraine Cross Award for innovation in medicine and science.

From 2014 to 2020, High served as the co-founder, President, Chief Scientific Officer/Head of R&D and a Member of the Board of Directors of Spark Therapeutics, a fully integrated, commercial gene therapy company in Philadelphia. While at Spark Therapeutics, Dr. High led the team that obtained the first FDA approval of an AAV therapeutic (Luxturna®) in December 2017 and led the team that obtained Breakthrough Therapy designations for three product candidates, SPK-RPE65 (Luxturna®), SPK-9001 for hemophilia B, and for SPK-8011 for hemophilia A.

In February 2020, High stepped down from her position at Spark Therapeutics as the company prepared to be absorbed by Swiss pharma Roche. [17]

In January 2021, High joined Asklepios Biopharmaceutical, or AskBio, a clinical-stage adeno-associated virus (AAV) gene therapy company and wholly owned subsidiary of Bayer AG, as the company's new President of Therapeutics and as a board member for AskBio. In this role, Dr. High is responsible for the development of the company's for driving the strategic direction and execution of the company's preclinical and clinical programs.

In April 2021, she was elected a member of the U. S. National Academy of Sciences. [18]

Personal life

She is married to George Steele, a nutritionist who was on the faculty of the University of Pennsylvania School of Medicine. [19] [20] She has three children, one of whom is actress Sarah Steele. [21] [22]

Related Research Articles

<span class="mw-page-title-main">Gene therapy</span> Medical field

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.

<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.

<span class="mw-page-title-main">Coagulation factor VII</span> Mammalian protein found in humans

Coagulation factor VII is one of the proteins that causes blood to clot in the coagulation cascade, and in humans is coded for by the 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.

<span class="mw-page-title-main">Adeno-associated virus</span> Species of virus

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).

Retinal gene therapy holds a promise in treating different forms of non-inherited and inherited blindness.

<span class="mw-page-title-main">Alipogene tiparvovec</span>

Alipogene tiparvovec, sold under the brand name Glybera, is a gene therapy treatment designed to reverse lipoprotein lipase deficiency (LPLD), a rare recessive disorder, due to mutations in LPL, which can cause severe pancreatitis. It was recommended for approval by the European Medicines Agency in July 2012 and approved by the European Commission in November of the same year. It was the first marketing authorisation for a gene therapy treatment in either Europe or the United States.

Self-complementary adeno-associated virus (scAAV) is a viral vector engineered from the naturally occurring adeno-associated virus (AAV) to be used as a tool for gene therapy. Use of recombinant AAV (rAAV) has been successful in clinical trials addressing a variety of diseases. This lab-made progeny of rAAV is termed "self-complementary" because the coding region has been designed to form an intra-molecular double-stranded DNA template. A rate-limiting step for the standard AAV genome involves the second-strand synthesis since the typical AAV genome is a single-stranded DNA template. However, this is not the case for scAAV genomes. Upon infection, rather than waiting for cell mediated synthesis of the second strand, the two complementary halves of scAAV will associate to form one double stranded DNA (dsDNA) unit that is ready for immediate replication and transcription. The caveat of this construct is that instead of the full coding capacity found in rAAV (4.7–6kb) scAAV can only hold about half of that amount (≈2.4kb).

James M. Wilson is a biomedical researcher with expertise in gene therapy. Wilson graduated from Albion College and the University of Michigan . He completed residency training in Internal Medicine at the Massachusetts General Hospital followed by a postdoctoral fellowship at the Whitehead Institute.

Saswati Chatterjee is a virologist working as a professor at the Los Angeles City of Hope National Medical Center in the research department. Some of the viral areas she researches are: stem cells, gene therapy, genome editing, and parvovirus. Her main and current area of research is using Adeno-Associated Virus Vectors (AAV-Vectors). Additionally, she has had a role in many publications.

<span class="mw-page-title-main">Spark Therapeutics</span> American pharmaceutical company

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

Richard Jude Samulski is an American scientist, inventor, and academic recognized for his pioneering work in gene therapy and adeno-associated virus vectors (AAV) in the fields of molecular virology and pharmacology.

Jean Bennett is the F. M. Kirby Professor of Ophthalmology in the Perelman School of Medicine at the University of Pennsylvania. Her research focuses on gene therapy for retinal diseases. Her laboratory developed the first FDA approved gene therapy for use in humans, which treats a rare form of blindness. She was elected a member of the National Academy of Sciences in 2022.

Mavis Agbandje-McKenna was a Nigerian-born British medical biophysicist, structural virologist, and a professor of structural biology, as well as the director of the Center for Structural Biology at the University of Florida in Gainesville, Florida. Agbandje-McKenna studied parvovirus structures using X-ray crystallography and cryogenic electron microscopy and did much of the initial work to elucidate the basic structure and function of adeno-associated viruses (AAVs). Her viral characterization and elucidation of antibody binding sites on AAV capsids has led to the development of viral capsid development and gene therapy approaches that evade immune detection and can be used to treat human diseases such as muscular dystrophies. Agbandje-McKenna was recognized with the 2020 American Society of Gene and Cell Therapy Outstanding Achievement Award for her contributions to the field. She died in 2021 from amyotrophic lateral sclerosis.

<span class="mw-page-title-main">Ultragenyx</span>

Ultragenyx is an American biopharmaceutical company involved in the research and development of novel products for treatment of rare and ultra-rare genetic diseases for which there are typically no approved treatments and high unmet medical need. The company works with multiple drug modalities including biologics, small molecule, gene therapies, and ASO and mRNAs in the disease categories of bone, endocrine, metabolic, muscle and CNS diseases.

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.

Etranacogene dezaparvovec, sold under the brand name Hemgenix is a gene therapy used for the treatment of hemophilia B. Etranacogene dezaparvovec is an adeno-associated virus vector-based gene therapy which consists of a viral vector carrying a gene for clotting Factor IX. The gene is expressed in the liver to produce Factor IX protein, to increase blood levels of Factor IX and thereby limit bleeding episodes. Hemophilia B is a genetic bleeding disorder resulting from missing or insufficient levels of blood clotting Factor IX, a protein needed to produce blood clots to stop bleeding.

ASC618 is an experimental gene therapy for Hemophilia A. It was developed by Applied StemCell Therapeutics and is delivered via a hybrid of adeno-associated virus types 2 and 8. The gene therapy is hoped to be more effective than earlier gene therapies for hemophilia A.

Fidanacogene elaparvovec, also known as SPK-9001 is an experimental gene therapy delivered via adeno-associated virus developed for Hemophilia B; it partially restores factor IX production in preliminary studies.

Dirloctogene samoparvovec, also known as SPK-8011, is an experimental gene therapy developed for hemophilia A by Roche and Spark Therapeutics.

References

  1. 1 2 Yarbrough, Cathy (3 September 2018). "Gene Therapy Pioneer's 30 Years Of Problem-Solving". Life Science Leader.
  2. ↑ "Katherine A. High | Faculty | About Us | Perelman School of Medicine | Perelman School of Medicine at the University of Pennsylvania". med.upenn.edu. Retrieved 6 November 2019.
  3. ↑ "Katherine High, M.D. | Board Member". Spark Therapeutics Inc. – IR Site. Archived from the original on 23 December 2019. Retrieved 6 November 2019.
  4. ↑ Wilson, James M. (1 December 2016). "Interview with Katherine A. High, MD". Human Gene Therapy Clinical Development. 27 (4): 127–131. doi:10.1089/humc.2016.29021.int. ISSN   2324-8637. PMID   27983889.
  5. 1 2 3 "Katherine A. High, MD". IHG Symposium 2015. 1 September 2015. Archived from the original on 14 September 2018. Retrieved 6 November 2019.
  6. ↑ Wilson, James M. (December 2016). "Interview with Katherine A. High, MD". Human Gene Therapy Clinical Development. 27 (4): 127–131. doi:10.1089/humc.2016.29021.int. ISSN   2324-8637. PMID   27983889.
  7. ↑ Kay MA, Manno CS, Ragni MV, Larson PJ, Couto LB, McClelland A, Glader B, Chew AJ, Tai SJ, Herzog RW, Arruda V, Johnson F, Scallan C, Skarsgard E, Flake AW, High KA (2000). "Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector". Nature Genetics. 24 (3): 257–261. doi:10.1038/73464. PMID   10700178. S2CID   12650196.
  8. ↑ Manno CS, Arruda VR, Pierce GF, Glader B, Ragni M, Rasko JJ, Ozelo MC, Hoots K, Blatt, P, Konkle B, Dake M, Kaye R, Razavi M, Zajko A, Zehnder J, Nakai H, Chew A, Leonard D, Wright JF, Lessard RR, Sommer JM, Tigges M, Sabatino D, Luk A, Jiang H, Mingozzi F, Couto L, Ertl HC, High KA, Kay MA (2006). "Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response". Nature Medicine. 12 (3): 342–347. doi:10.1038/nm1358. PMID   16474400. S2CID   14664182.
  9. ↑ Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell'osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J (April 28, 2008). "Safety and efficacy of gene transfer for Leber's Congenital Amaurosis". New England Journal of Medicine. 358 (21): 2240–2248. doi:10.1056/NEJMoa0802315. PMC   2829748 . PMID   18441370.
  10. ↑ "Factor This! Series: An Interview with Dr. Katherine A. High ·". onthepulseconsultancy.com. 19 January 2018. Retrieved 6 November 2019.
  11. ↑ Evans, J. P.; Watzke, H. H.; Ware, J. L.; Stafford, D. W.; High, K. A. (July 1989). "Molecular cloning of a cDNA encoding canine factor IX". Blood. 74 (1): 207–212. doi: 10.1182/blood.V74.1.207.207 . ISSN   0006-4971. PMID   2752110.
  12. ↑ Chaing, S.; Clarke, B.; Sridhara, S.; Chu, K.; Friedman, P.; VanDusen, W.; Roberts, H. R.; Blajchman, M.; Monroe, D. M.; High, K. A. (1994-06-15). "Severe factor VII deficiency caused by mutations abolishing the cleavage site for activation and altering binding to tissue factor". Blood. 83 (12): 3524–3535. doi: 10.1182/blood.V83.12.3524.3524 . ISSN   0006-4971. PMID   8204879.
  13. ↑ Herzog, R. W.; Yang, E. Y.; Couto, L. B.; Hagstrom, J. N.; Elwell, D.; Fields, P. A.; Burton, M.; Bellinger, D. A.; Read, M. S.; Brinkhous, K. M.; Podsakoff, G. M. (January 1999). "Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector". Nature Medicine. 5 (1): 56–63. doi:10.1038/4743. ISSN   1078-8956. PMID   9883840. S2CID   21832836.
  14. ↑ "Dr. Jean Bennett & Dr. Katherine High Win $1 Million Sanford Lorraine Cross Award". Smithsonian. Retrieved 6 November 2019.
  15. ↑ "Katherine High" (PDF). Retrieved 1 October 2017.
  16. ↑ "Katherine A. High, MD - IHG Symposium 2015". IHG Symposium 2015. 1 September 2015. Archived from the original on 14 September 2018. Retrieved 1 October 2017.
  17. ↑ "Spark Co-Founder Katherine High Departs Company Ahead of Merger with Roche". BioSpace. Retrieved 25 February 2020.
  18. ↑ "News from the National Academy of Sciences". 26 April 2021. Retrieved 2 July 2021. Newly elected members and their affiliations at the time of election are: ... High, Katherine A.; president, Therapeutics, AskBio, Research Triangle Park, N.C.
  19. ↑ "Growing into her biggest film role". Los Angeles Times. 26 December 2004. Retrieved 17 July 2020.
  20. ↑ Elkin, Michael (26 July 2013). "Sarah Steele finding herself on everybody's to-hire list". inquirer.com. Retrieved 17 July 2020.
  21. ↑ admin (30 May 2018). "Pulling Back the Curtain: Katherine A. High, MD". ASH Clinical News. Retrieved 17 July 2020.
  22. ↑ Healy, Patrick (28 June 2012). "Role After Role, She Cuts Years Off Her Age". The New York Times. ISSN   0362-4331 . Retrieved 17 July 2020.
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