Wikipedia

Robert J. Desnick

Robert J. Desnick is an American human geneticist whose basic and translational research accomplishments include significant discoveries in genomics, pharmacogenetics, gene therapy, personalized medicine, and the treatment of genetic diseases. His translational research has led to the development of the enzyme replacement therapy (ERT) and the chaperone therapy for Fabry disease,[1][2] ERT for Niemann–Pick disease type B, and the RNA Interference Therapy for the Acute Hepatic Porphyrias.[3]

Robert J. Desnick
Born
Minneapolis, MN
NationalityAmerican
Alma materUniversity of Minnesota Medical School
Known fortranslational research in genetics and genomics; research on inherited metabolic diseases
AwardsE. Mead Johnson Award (1981)
Scientific career
Fieldshuman genetics and genomics
InstitutionsMount Sinai Hospital

He was the co-founder of Amicus Therapeutics, a biopharmaceutical company developing pharmacologic chaperone therapies (Galafold approved 2018[4]), and served as the Chairman of the Scientific Advisory Committees (SAC) of Synageva BioPharma [5] and Kiniksa Pharmaceuticals. The enzyme therapy developed in his laboratory and licensed to Genzyme as Fabrazyme, along with Cerazyme for Gaucher disease, helped build the rare disease company Genzyme, which has spawned more CEOs than any other company in history following its 2011 sale to Sanofi for $20.1 billion.[6]

Desnick is the Dean for Genetics and Genomic Medicine, and Professor and Chairman Emeritus of the Department of Genetics & Genomic Sciences at The Icahn School of Medicine at Mount Sinai in New York City. Additionally, he is Professor of Pediatrics, Professor of Oncological Sciences, and Professor of Obstetrics, Gynecology and Reproductive Science at The Mount Sinai Hospital.

Desnick is the author of more than 590 peer-reviewed articles in scientific journals, 250 book chapters and is the editor of 10 books. He holds 26 US issued and licensed patents[7] and is included in Castle Connelly's lists of Best Doctors in America and Best Doctors in New York and New York Magazine’s list of the Best Doctors every year since the inception of the rating.[8][9] He was elected to the National Academies of Sciences, Engineering and Medicine in 2004.[10]

Part of his genetics laboratory at Mount Sinai was spun out into Sema4 (NASDAQ: SMFR), which IPO’d in 2021 for $3 billion.

Biography

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Desnick received his undergraduate degree from the University of Minnesota in 1965. He earned a Ph.D. in genetics from the University of Minnesota Graduate School in 1970 and his M.D. from the University of Minnesota Medical School in 1971. He completed an internship and a residency in pediatrics at the University of Minnesota Hospitals and joined the faculty at the University of Minnesota, where he rose to the rank of associate professor of Cell Biology and Genetics and Pediatrics.

Desnick joined the staff at Mount Sinai Medical Center in 1977, as the Arthur J. and Nellie Z. Cohen Professor of Pediatrics and Genetics and Chief of the Division of Medical and Molecular Genetics. He was the first chairman of the newly created Department of Human Genetics in 1993, which was renamed the Department of Genetics & Genomic Sciences in 2006. In 2009, he became Dean for Genetics & Genomic Medicine and Interim Director of the newly established Genomics Institute at Mount Sinai. He is currently Professor of Pediatrics, Oncological Sciences, Obstetrics, Gynecology and Reproductive Science, Gene and Cell Medicine and Professor and Chairman Emeritus of Genetics & Genomic Sciences.[11]

Desnick is an elected member of the Society for Pediatric Research, the American Pediatric Society, the American Society for Clinical Investigation, and the Association of American Physicians. He is an elected Fellow of the American Association for the Advancement of Science, and an elected member of the National Academy of Medicine of the National Academy of Sciences.[12] His research awards include the E. H. Ahrens, Jr. Award for Research from the Association for Patient-Oriented Research and the Award for Excellence in Clinical Research from the National Center for Research Resources from the National Institutes of Health. He received the Outstanding Achievement Award from the University of Minnesota.

Desnick is a past director of the American Board of Medical Genetics, a Founding Diplomat of the American College of Medical Genetics, a past member of the board of directors of the American College of Medical Genetics Foundation, and a founder and past president of the Association of Professors of Human and Medical Genetics.[13][14] He is past chair of the Association of American Medical Colleges (AAMC), past member of the AAMC Board of Directors and past chair of the AAMC Council of Academic Societies. He is currently the President of the American Porphyrias Expert Collaborative.

Personal life

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He lives in New York City and Palm Beach with his wife, Julie Herzig Desnick, and son, Jonathan Desnick. Julie is an Abstract Expressionist painter and a LEED-certified, Registered Architect.

He is a Trustee of the American School of Classical Studies in Athens.[15]

Fellowships and awards

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Partial list:

Grants

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Partial list:[13]

Patents

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  • Cloning and expression of biologically active human alpha-galactosidase A, (1994).[21]
  • Cloning and expression of biologically active α-N-acetylgalactosaminidase, (1995).[22]
  • Cloning and expression of biologically active α-galactosidase A, (1995).[23]
  • Cloning and expression of biologically active α-N-acetylgalactosaminidase, (1996).[24]
  • Cloning and expression of biologically active alpha-galactosidase A as a fusion protein, (1996).[25]
  • Acid sphingomyelinase gene and diagnosis of Niemann-Pick disease, (1997).[26]
  • Acid sphingomyelinase gene, (1998).[27]
  • Methods for the treatment of bone resorption disorders, including osteoporosis, (1998).[28]
  • Methods for determining susceptibility to lead poisoning, (1998).[29]
  • Cells expressing an αGalA nucleic acid and methods of xenotransplantation, (2002).[30]
  • Acid sphingomyelinase protein and methods of treating type B Niemann-Pick disease, (2003).[31]
  • Method for enhancing mutant enzyme activities in lysosomal storage disorders, (2003).[32]
  • Chaperone-based therapy for Niemann-Pick disease, (2010).[33]
  • Dose escalation enzyme replacement therapy for treating acid sphingomyelinase deficiency, (2013).[34]
  • Dose escalation enzyme replacement therapy for treating acid sphingomyelinase deficiency, (2014).[35]
  • Dose escalation enzyme replacement therapy for treating acid sphingomyelinase deficiency, (2014).[36]
  • Compositions and methods for inhibiting expression of the ALAS1 gene, (2015).[37]
  • Method and kits for detecting a polymorphism in δ-aminolevulinate dehydratase gene which is associated with an altered susceptibility to lead poisoning, (2017).[38]
  • Dose escalation enzyme replacement therapy for treating acid sphingomyelinase deficiency, (2017).[39]
  • Compositions and methods for inhibiting expression of the ALAS1 gene, (2017).[40]
  • Dose escalation enzyme replacement therapy for treating acid sphingomyelinase deficiency, (2017).[41]
  • Materials and methods for identifying spinal muscular atrophy carriers, (2018).[42]
  • Compositions and methods for inhibiting expression of the ALAS1 gene, (2018).[43]
  • Compositions and methods for inhibiting expression of the ALAS1 gene, (2018).[44]
  • Dose escalation enzyme replacement therapy for treating acid sphingomyelinase deficiency, (2019).[45]
  • Compositions and methods for inhibiting expression of the ALAS1 gene, (2021).[46]

Books

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  • Desnick, R. J., Bernlohr, R. W. and Krivit, W., eds.: Enzyme Therapy in Genetic Diseases, Birth Defects Original Article Series. Vol. IX, No. 2. The National Foundation, New York, pp. 236, 1973. ISBN 0-683-06367-7
  • Rubenstein, I., Phillips, R. L., Green, C. E. and Desnick, R. J., eds.: Molecular Genetic Modification of Eucaryotes, Academic Press, New York, pp. 171, 1977. ASIN B000N5X2F2
  • Desnick, R. J., ed.: Enzyme Therapy in Genetic Diseases: 2, Alan R. Liss, Inc., New York, pp. 544, 1980. ISBN 0-8451-1035-7
  • Desnick, R. J., Patterson, D. F. and Scarpelli, D. F., eds.: Animal Models of Inherited Metabolic Diseases. Alan R. Liss, Inc., New York, pp. 519, 1982. ASIN B0028IQ4KC
  • Desnick, R. J., Gatt, S. and Grabowski, G. A., eds.: Gaucher Disease: A Century of Delineation and Research, Alan R. Liss, Inc., New York, pp. 740, 1982. ISBN 0-8451-0095-5
  • Bishop, D. F. and Desnick, R. J., eds.: Assays of the Heme Biosynthetic Enzymes. Enzyme 28:1–232, 1982. ISBN 978-3-8055-3573-1
  • Tada, K., Colombo, J. P. and Desnick, R. J., eds.: Recent Advances in Inborn Errors of Metabolism. Karger, Basel, pp. 332, 1987. ISBN 3-8055-4772-2
  • Desnick, R. J., ed.: Treatment of Genetic Diseases, Churchill Livingstone, Inc., New York, pp. 331, 1991. ISBN 0-443-08773-3
  • Desnick, R. J. and Kaback, M. M., eds.: Tay–Sachs Disease, Academic Press, pp. 1–360, 2001. ISBN 0-12-017644-0

Publications

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Partial list:

  • Ziegler, RJ, Cherry, M, Barbon, CM, Li, C, Bercury, SD, Armentano, D, Desnick, RJ, Cheng, SH: Correction of the biochemical and functional deficits in Fabry mice following AAV8-mediated hepatic expression of alpha-galactosidase A Mol. Ther. 15:492–500, 2007. doi:10.1038/sj.mt.6300066 PMID 17191071
  • Germain, DP, Waldek, S, Banikazemi, M, Bushinsky, DA, Charrow, J, Desnick, RJ, Lee, P, Loew, T, Vedder, AC, Abichandani, R, Wilcox, WR, and Guffon, N: Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease J. Am. Soc. Nephrol. 18:1547–1557, 2007. doi:10.1681/ASN.2006080816 PMID 17409312
  • Grace, ME, Balwani, M, Nazarenko, I, Prakash-Cheng, A, and Desnick, RJ: Type 1 Gaucher disease: Null and hypomorphic novel chitotriosidase mutations- implications for diagnosis and therapeutic monitoring. Hum. Mutat. 28:866–873, 2007. doi:10.1002/humu.20524 PMID 17464953
  • Desnick, R. J: Prenatal diagnosis of Fabry disease Prenat. Diag. 27:693–694, 2007. doi:10.1002/pd.1767 PMID 17533632
  • Scott, SA, Edelmann, L, Kornreich, R, Erazo, M and Desnick, RJ: CYP2C9, CYP2C19, and CYP2D6 allele frequencies in the Ashkenazi Jewish population. Pharmacogenomics 8:721–730, 2007. doi:10.2217/14622416.8.7.721 PMID 18240905
  • Yasuda, M, Domaradzki, M, Bishop, DF, and Desnick, RJ: Acute intermittent porphyria: Vector optimization for gene therapy J. Gene Med. 9:806–911, 2007. doi:10.1002/jgm.1074 PMID 17654633
  • Cunha, L, Kuti, M, Bishop, DF, Mezei, M, Zeng, L, Zhou, MM and Desnick, RJ: Human uroporphyrinogen III synthase: NMR-based mapping of the active site. Proteins 71:855–873, 2008. doi:10.1002/prot.21755 PMID 18004775
  • Scott, SA, Edelmann, L, Kornreich, R and Desnick, RJ: Warfarin pharmacogenetics: CYP2C9 and VKORC1 genotype predict different sensitivities and resistance frequencies in the Ashkenazi and Sephardi Jewish populations. Am. J. Hum. Genet. 82:495–500, 2008. doi:10.1016/j.ajhg.2007.10.002 PMID 18252229
  • McGovern, MM, Wasserstein, MP, Giugliani, R, Bembi, B, Vanier, M, Mengel, E, Brodie, SE, Mendelson, D, Skloot, G, Schuchman, EH Kuriyama, N, Desnick, RJ, and Cox, GF: A prospective, cross-sectional survey study of the natural history of Niemann-Pick disease Type B. Pediatrics 122: e341-349, 2008. doi:10.1542/peds.2007-3016 PMID 18625664
  • Schiffmann, R, Banikazemi, M, Bultas, J, Linthorst, GE, Packman, S, Warnock, D, Asger Sorensen, S, Wilcox, WR, and Desnick, RJ: Fabry disease: progression of nephropathy, and prevalence of cardiac and cerebrovascular events before enzyme replacement therapy Nephrol. Dial. Transplant. 24:2102–2111, 2009. doi:10.1093/ndt/gfp031 PMID 19218538
  • Benjamin, ER, Flanagan, JJ, Schilling, A, Chang, HH, Agarwal, L, Datz, E, Wu, X, Pine, C, Wustman, B, Desnick, RJ, Lockhart, DJ, and Valenzano, KJ: The pharmacological chaperone 1-deoxygalactonojirimycin increases α-galactosidase A levels in Fabry patient cell lines. J. Inherit. Dis. 3:424–440, 2009. doi:10.1007/s10545-009-1077-0 PMID 19387866
  • Hwu, WL, Chien, YH, Lee, NC, Chiang, SC, Huang, AC, Yeh, HY, Chao, MC, Lin, SJ, Kitagawa, T, Hse, LW, Desnick, RJ, and Hsu, LW: Newborn screening for Fabry disease in Taiwan reveals a high incidence of the later-onset mutation, IVS4+919G>A. Hum. Mutat., June 26, 2009. PMID 19621417
  • Scott, SA, Jaremko, M, Lubitz, S, Halperin, JL, Desnick, RJ: CYP2C9*8 is prevalent in African-Americans: implications for pharmacogenetic dosing. Pharmacogenomics 10:1243–1255, 2009. PMID 1963669
  • Galende, E., Karakikes, I., Edelmann, L., Desnick, R. J., Kerenyi, T., Khoueiry, G., Lafferty, J., McGinn, J. T., Brodman, M., Fuster, V., Hajjar, R. J., and Polgar, K. Amniotic fluid cells are more efficiently reprogrammed to pluripotency than adult cells. Cloning Stem Cells [Epub] Dec. 17, 2009. PMID 20677926 doi:10.1089/cell.2009.0077
  • Khanna, R, Soska, R, Lun, Y, Feng, J, Frascella, M, Young, B, Brignol, N, Pellegrino, L, Sitaraman, SA, Desnick, RJ, Benjamin, ER, Lockhart, DJ and Valenzano, KJ: The pharmacological chaperone 1-deoxygalactonojirimycin reduces tissue globotriaosylceramide levels in a mouse model of Fabry disease. Mol. Ther. 18:23–33, 2010. doi:10.1038/mt.2009.220 PMID 19773742
  • Yasuda, M, Bishop, DF, Gan, L, Fowkes, M, Ziegler, R, Cheng, SH, and Desnick, RJ: AAV8-mediated gene therapy prevents induced biochemical attacks of acute intermittent porphyria. Mol. Ther. 18:17–22, 2010. doi:10.1038/mt.2009.250 PMID 19861948
  • Wozniak, M, Kittner, S, Tuhrim, S, Cole, J, Stern, B, Dobbins, M, Grace, M, Nazarenko, I, Dobrovolny, R, McDade, E, Desnick, RJ: Frequency of unrecognized Fabry disease among young European-American and African-American men with first ischemic stroke. Stroke 41: 78–81, 2010. doi:10.1161/STROKEAHA.109.558320 PMID 20007919

References

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  1. ^ Katie Charles (2008-12-31). "An infusion of hope: Genetic engineering is changing the lives of kids and adults with Fabry Disease". New York Daily News. Retrieved 2010-03-01.
  2. ^ "The American Porphyria Foundation". Retrieved 2010-03-01.
  3. ^ "Alnylam Announces Approval of GIVLAARI® (givosiran) in the European Union for the Treatment of Acute Hepatic". Investor Relations | Alnylam Pharmaceuticals, Inc. Retrieved 2020-08-11.
  4. ^ "FDA Approves Galafold™ (Migalastat) for the Treatment of Certain Adult Patients with Fabry Disease - New York Times". Archived from the original on 2018-09-06. Retrieved 2018-09-05.
  5. ^ "Alexion To Acquire To Strengthen Global Leadership". Retrieved 3 January 2018.
  6. ^ Robert Weisman (July 11, 2015). "How Genzyme became a source of biotech executives". The Boston Globe. Retrieved 2021-05-05.
  7. ^ "United States Patent Office". Retrieved 2010-03-01.
  8. ^ "National Organization for Rare Disorders, Inc". Archived from the original on 2009-07-25. Retrieved 2010-03-01.
  9. ^ "New York Magazine: Best Doctors 2009". Retrieved 2010-03-01.
  10. ^ "Directory – Institute of Medicine". Retrieved 2010-03-01.
  11. ^ "Mount Sinai Hospital – Doctor profile". Retrieved 2015-04-09.
  12. ^ "Awards, Appointments, Announcements". Journal of the National Cancer Institute. 96 (22): 1658. 2004-11-17. doi:10.1093/jnci/96.22.1658.
  13. ^ a b "ResearchCrossroads". Archived from the original on July 27, 2011. Retrieved 2010-03-01.
  14. ^ "MyNewsdesk". Retrieved 2010-03-01.[dead link‍]
  15. ^ "Trustee List". ASCSA.
  16. ^ "Alumni Award Recipients". alumni.icahn.mssm.edu. Retrieved 2019-03-13.
  17. ^ "Distinguished Alumni Award". Medical School – University of Minnesota. 11 November 2014. Retrieved April 29, 2016.
  18. ^ "Two Mount Sinai Researchers Named "Inventors of the Year" by the New York Intellectual Property Law Association | Mount Sinai Innovation Partners". 28 June 2013. Retrieved 2019-03-13.
  19. ^ "Dr. Robert J. Desnick, MD, Ph.D - 2017 Rare Impact Award Honoree". NORD (National Organization for Rare Disorders). 2017-03-15. Retrieved 2019-03-13.
  20. ^ "CBS Recognizes Three Outstanding Alumni | College of Biological Sciences". cbs.umn.edu. Retrieved 2019-03-13.
  21. ^ US 5356804, Desnick, Robert J.; Bishop, David F. & Ioannou, Yiannis A., "Cloning and expression of biologically active human alpha-galactosidase A", published 1994-10-18, assigned to Mount Sinai School of Medicine of New York University 
  22. ^ US 5382524, Desnick, Robert J.; Bishop, David F. & Ioannou, Yiannis A. et al., "Cloning and expression of biologically active α-N-acetylgalactosaminidase", published 1995-01-17, assigned to Mount Sinai School of Medicine of New York University 
  23. ^ US 5401650, Desnick, Robert J.; Bishop, David F. & Ioannou, Yiannis A., "Cloning and expression of biologically active α-galactosidase A", published 1995-03-28, assigned to Mount Sinai School of Medicine of New York University 
  24. ^ US 5491075, Desnick, Robert J.; Bishop, David F. & Ioannou, Yiannis A. et al., "Cloning and expression of biologically active alpha N-acetylgalactosaminidase", published 1996-02-13, assigned to Mount Sinai School of Medicine of New York University 
  25. ^ US 5580757, Gelb, Bruce D.; Chapman, Harold & Desnick, Robert J., "Cloning and expression of biologically active α-galactosidase A as a fusion protein", published 1996-12-03, assigned to Mount Sinai School of Medicine of New York University 
  26. ^ US 5686240, Schuchman, Edward H. & Desnick, Robert J., "Acid sphingomyelinase gene and diagnosis of Niemann-Pick disease", published 1997-11-11, assigned to Mount Sinai School of Medicine of New York University 
  27. ^ US 5773278, Schuchman, Edward H. & Desnick, Robert J., "Acid sphingomyelinase gene", published 1998-06-30, assigned to Mount Sinai School of Medicine of New York University 
  28. ^ US 5830850, Gelb, Bruce D.; Chapman, Harold & Desnick, Robert J., "Methods for the treatment of bone resorption disorders, including osteoporosis", published 1998-11-03, assigned to Mount Sinai School of Medicine of New York University and Brigham and Women's Hospital 
  29. ^ US 5840578, Desnick, Robert J. & Wetmur, James G., "Methods for determining susceptibility to lead poisoning", published 1998-11-24, assigned to Mount Sinai School of Medicine of New York University 
  30. ^ US 6455037, Ioannou, Yiannis; Desnick, Robert J. & Sandrin, Mauro S. et al., "Cells expressing an αGalA nucleic acid and methods of xenotransplantation", published 2002-09-24, assigned to Mount Sinai School of Medicine of New York University and The Austin Research Institute 
  31. ^ US 6541218, Schuchman, Edward H. & Desnick, Robert J., "Acid sphingomyelinase protein and methods of treating type B Niemann-Pick disease", published 2003-04-01, assigned to Mount Sinai School of Medicine of New York University 
  32. ^ US 6583158, Fan, Jian-Qiang; Ishii, Satoshi & Asano, Naoki et al., "Method for enhancing mutant enzyme activities in lysosomal storage disorders", published 2003-06-24, assigned to Mount Sinai School of Medicine of New York University 
  33. ^ US 7750050, Schuchman, Edward H. & Desnick, Robert J., "Chaperone-based therapy for Niemann-Pick disease", published 2010-07-06, assigned to Mount Sinai School of Medicine of New York University 
  34. ^ US 8349319, Schuchman, Edward H.; Desnick, Robert J. & Cox, Gerald F. et al., "Dose escalation enzyme replacement therapy for treating acid sphingomyelinase deficiency", published 2013-01-08, assigned to Icahn School of Medicine at Mount Sinai and Genzyme Corp. 
  35. ^ US 8658162, Schuchman, Edward H.; Desnick, Robert J. & Cox, Gerald F. et al., "Dose escalation enzyme replacement therapy for treating acid sphingomyelinase deficiency", published 2014-02-25, assigned to Icahn School of Medicine at Mount Sinai and Genzyme Corp. 
  36. ^ US 8709408, Schuchman, Edward H.; Desnick, Robert J. & Cox, Gerald F. et al., "Dose escalation enzyme replacement therapy for treating acid sphingomyelinase deficiency", published 2014-04-29, assigned to Icahn School of Medicine at Mount Sinai and Genzyme Corp. 
  37. ^ US 9133461, Bettencourt, Brian; Fitzgerald, Kevin & Querbes, William et al., "Compositions and methods for inhibiting expression of the ALAS1 gene", published 2015-09-15, assigned to Alnylam Pharmaceuticals Inc. and Icahn School of Medicine at Mount Sinai 
  38. ^ US 5639607, Desnick, Robert J. & Wetmur, James G., "Method and kits for detecting a polymorphism in δ-aminolevulinate dehydratase gene which is associated with an altered susceptibility to lead poisoning", published 1997-06-17, assigned to Mount Sinai School of Medicine of New York University 
  39. ^ US 9655954, Schuchman, Edward H.; Desnick, Robert J. & Cox, Gerald F. et al., "Dose escalation enzyme replacement therapy for treating acid sphingomyelinase deficiency", published 2017-05-23, assigned to Icahn School of Medicine at Mount Sinai and Genzyme Corp. 
  40. ^ US 9631193, Bettencourt, Brian; Fitzgerald, Kevin & Querbes, William et al., "Compositions and methods for inhibiting expression of the ALAS1 gene", published 2017-04-25, assigned to Alnylam Pharmaceuticals Inc. and Icahn School of Medicine at Mount Sinai 
  41. ^ US 9655954, Schuchman, Edward H.; Desnick, Robert J. & Cox, Gerald F. et al., "Dose escalation enzyme replacement therapy for treating acid sphingomyelinase deficiency", published 2017-05-23, assigned to Icahn School of Medicine at Mount Sinai and Genzyme Corp. 
  42. ^ US 9994898, Edelmann, Lisa & Desnick, Robert J., "Materials and methods for identifying spinal muscular atrophy carriers", published 2018-06-12, assigned to Icahn School of Medicine at Mount Sinai 
  43. ^ US 10119143, Bettencourt, Brian; Fitzgerald, Kevin & Querbes, William et al., "Compositions and methods for inhibiting expression of the ALAS1 gene", published 2018-11-06, assigned to Alnylam Pharmaceuticals Inc. and Icahn School of Medicine at Mount Sinai 
  44. ^ US 10125364, Bettencourt, Brian; Fitzgerald, Kevin & Querbes, William et al., "Compositions and methods for inhibiting expression of the ALAS1 gene", published 2018-11-13, assigned to Alnylam Pharmaceuticals Inc. and Icahn School of Medicine at Mount Sinai 
  45. ^ US 10188705, Schuchman, Edward H.; Desnick, Robert J. & Cox, Gerald F et al., "Dose escalation enzyme replacement therapy for treating acid sphingomyelinase deficiency", published 2019-01-29, assigned to Icahn School of Medicine at Mount Sinai and Genzyme Corp. 
  46. ^ US 11028392, Bettencourt, Brian; Fitzgerald, Kevin & Querbes, William et al., "Compositions and methods for inhibiting expression of the ALAS1 gene", published 2021-06-08, assigned to Alnylam Pharmaceuticals Inc. and Icahn School of Medicine at Mount Sinai 
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