Skip to main content

Tipp

Weitere Artikel dieser Ausgabe durch Wischen aufrufen

Erschienen in: Wiener Medizinische Wochenschrift 9-10/2017

01.06.2017 | main topic

Orphan diseases: state of the drug discovery art

verfasst von: PhD Claude-Henry Volmar, MD, PhD Claes Wahlestedt, PhD Shaun P. Brothers

Erschienen in: Wiener Medizinische Wochenschrift | Ausgabe 9-10/2017

Einloggen, um Zugang zu erhalten
share
TEILEN

Summary

Since 1983 more than 300 drugs have been developed and approved for orphan diseases. However, considering the development of novel diagnosis tools, the number of rare diseases vastly outpaces therapeutic discovery. Academic centers and nonprofit institutes are now at the forefront of rare disease R&D, partnering with pharmaceutical companies when academic researchers discover novel drugs or targets for specific diseases, thus reducing the failure risk and cost for pharmaceutical companies. Considerable progress has occurred in the art of orphan drug discovery, and a symbiotic relationship now exists between pharmaceutical industry, academia, and philanthropists that provides a useful framework for orphan disease therapeutic discovery. Here, the current state-of-the-art of drug discovery for orphan diseases is reviewed. Current technological approaches and challenges for drug discovery are considered, some of which can present somewhat unique challenges and opportunities in orphan diseases, including the potential for personalized medicine, gene therapy, and phenotypic screening.
Literatur
2.
Zurück zum Zitat Wästfelt M, Fadeel B, Henter J-I. A journey of hope: lessons learned from studies on rare diseases and orphan drugs. J Intern Med. 2006;260:1–10. CrossRefPubMed Wästfelt M, Fadeel B, Henter J-I. A journey of hope: lessons learned from studies on rare diseases and orphan drugs. J Intern Med. 2006;260:1–10. CrossRefPubMed
3.
Zurück zum Zitat Haffner ME, Whitley J, Moses M. Two decades of orphan product development. Nat Rev Drug Discov. 2002;1:821–5. CrossRefPubMed Haffner ME, Whitley J, Moses M. Two decades of orphan product development. Nat Rev Drug Discov. 2002;1:821–5. CrossRefPubMed
4.
Zurück zum Zitat Dolgin E. Big pharma moves from “blockbusters” to “niche busters”. Nat Med. 2010;16:837–7. Dolgin E. Big pharma moves from “blockbusters” to “niche busters”. Nat Med. 2010;16:837–7.
5.
Zurück zum Zitat Dunne S, Shannon B, Dunne C, Cullen W. A review of the differences and similarities between generic drugs and their originator counterparts, including economic benefits associated with usage of generic medicines, using Ireland as a case study. BMC Pharmacol Toxicol. 2013;14:1. CrossRefPubMedPubMedCentral Dunne S, Shannon B, Dunne C, Cullen W. A review of the differences and similarities between generic drugs and their originator counterparts, including economic benefits associated with usage of generic medicines, using Ireland as a case study. BMC Pharmacol Toxicol. 2013;14:1. CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Haffner ME, Torrent-Farnell J, Maher PD. Does orphan drug legislation really answer the needs of patients? Lancet. 2008;371:2041–4. CrossRefPubMed Haffner ME, Torrent-Farnell J, Maher PD. Does orphan drug legislation really answer the needs of patients? Lancet. 2008;371:2041–4. CrossRefPubMed
8.
Zurück zum Zitat Hershfield MS, Buckley RH, Greenberg ML, Melton AL, Schiff R, Hatem C, et al. Treatment of adenosine deaminase deficiency with polyethylene glycol–modified adenosine deaminase. N Engl J Med. 1987;316:589–96. CrossRefPubMed Hershfield MS, Buckley RH, Greenberg ML, Melton AL, Schiff R, Hatem C, et al. Treatment of adenosine deaminase deficiency with polyethylene glycol–modified adenosine deaminase. N Engl J Med. 1987;316:589–96. CrossRefPubMed
9.
11.
Zurück zum Zitat Brewer GJ. Drug development for orphan diseases in the context of personalized medicine. Transl Res 2009;154:314–22. CrossRefPubMed Brewer GJ. Drug development for orphan diseases in the context of personalized medicine. Transl Res 2009;154:314–22. CrossRefPubMed
12.
Zurück zum Zitat Futerman AH, van Meer G. The cell biology of lysosomal storage disorders. Nat Rev Mol Cell Biol. 2004;5:554–65. CrossRefPubMed Futerman AH, van Meer G. The cell biology of lysosomal storage disorders. Nat Rev Mol Cell Biol. 2004;5:554–65. CrossRefPubMed
13.
Zurück zum Zitat Platt FM, Boland B, van der Spoel AC. Lysosomal storage disorders: the cellular impact of lysosomal dysfunction. J Cell Biol. 2012;199:723–34. CrossRefPubMedPubMedCentral Platt FM, Boland B, van der Spoel AC. Lysosomal storage disorders: the cellular impact of lysosomal dysfunction. J Cell Biol. 2012;199:723–34. CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Parenti G, Andria G, Ballabio A. Lysosomal storage diseases: from pathophysiology to therapy. Annu Rev Med. 2015;66:471–86. CrossRefPubMed Parenti G, Andria G, Ballabio A. Lysosomal storage diseases: from pathophysiology to therapy. Annu Rev Med. 2015;66:471–86. CrossRefPubMed
15.
Zurück zum Zitat Xu K, Coté TR. Database identifies FDA-approved drugs with potential to be repurposed for treatment of orphan diseases. Brief Bioinform. 2011. doi: 10.​1093/​bib/​bbr006. Xu K, Coté TR. Database identifies FDA-approved drugs with potential to be repurposed for treatment of orphan diseases. Brief Bioinform. 2011. doi: 10.​1093/​bib/​bbr006.
16.
18.
Zurück zum Zitat Janovick JA, Brothers SP, Cornea A, Bush E, Goulet MT, Ashton WT, et al. Refolding of misfolded mutant GPCR: post-translational pharmacoperone action in vitro. Mol Cell Endocrinol. 2007;272:77–85. CrossRefPubMedPubMedCentral Janovick JA, Brothers SP, Cornea A, Bush E, Goulet MT, Ashton WT, et al. Refolding of misfolded mutant GPCR: post-translational pharmacoperone action in vitro. Mol Cell Endocrinol. 2007;272:77–85. CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Hanrahan JW, Sampson HM, Thomas DY. Novel pharmacological strategies to treat cystic fibrosis. Trends Pharmacol Sci. 2013;34:119–25. CrossRefPubMed Hanrahan JW, Sampson HM, Thomas DY. Novel pharmacological strategies to treat cystic fibrosis. Trends Pharmacol Sci. 2013;34:119–25. CrossRefPubMed
20.
Zurück zum Zitat Wang G-N, Reinkensmeier G, Zhang S-W, Zhou J, Zhang L-R, Zhang L-H, et al. Rational design and synthesis of highly potent pharmacological chaperones for treatment of N370S mutant Gaucher disease. J Med Chem. 2009;52:3146–9. CrossRefPubMed Wang G-N, Reinkensmeier G, Zhang S-W, Zhou J, Zhang L-R, Zhang L-H, et al. Rational design and synthesis of highly potent pharmacological chaperones for treatment of N370S mutant Gaucher disease. J Med Chem. 2009;52:3146–9. CrossRefPubMed
21.
Zurück zum Zitat Brothers SP, Janovick JA, Conn PM. Calnexin regulated gonadotropin-releasing hormone receptor plasma membrane expression. J Mol Endocrinol. 2006;37:479–88. CrossRefPubMed Brothers SP, Janovick JA, Conn PM. Calnexin regulated gonadotropin-releasing hormone receptor plasma membrane expression. J Mol Endocrinol. 2006;37:479–88. CrossRefPubMed
22.
Zurück zum Zitat Swinney DC, Anthony J. How were new medicines discovered? Nat Rev Drug Discov. 2011;10:507–19. CrossRefPubMed Swinney DC, Anthony J. How were new medicines discovered? Nat Rev Drug Discov. 2011;10:507–19. CrossRefPubMed
23.
Zurück zum Zitat Moffat JG, Rudolph J, Bailey D. Phenotypic screening in cancer drug discovery—past, present and future. Nat Rev Drug Discov. 2014;13:588–602. CrossRefPubMed Moffat JG, Rudolph J, Bailey D. Phenotypic screening in cancer drug discovery—past, present and future. Nat Rev Drug Discov. 2014;13:588–602. CrossRefPubMed
24.
Zurück zum Zitat Marks PA, Breslow R. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol. 2007;25:84–90. CrossRefPubMed Marks PA, Breslow R. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol. 2007;25:84–90. CrossRefPubMed
25.
Zurück zum Zitat Ferlini A, Scotton C, Novelli G. Biomarkers in rare diseases. Public Health Genomics. 2013;16:313–21. CrossRefPubMed Ferlini A, Scotton C, Novelli G. Biomarkers in rare diseases. Public Health Genomics. 2013;16:313–21. CrossRefPubMed
27.
Zurück zum Zitat Kesselheim AS, Gagne JJ. Strategies for postmarketing surveillance of drugs for rare diseases. Clin Pharmacol Ther. 2014;95:265–8. CrossRefPubMed Kesselheim AS, Gagne JJ. Strategies for postmarketing surveillance of drugs for rare diseases. Clin Pharmacol Ther. 2014;95:265–8. CrossRefPubMed
29.
Zurück zum Zitat Griggs RC, Batshaw M, Dunkle M, Gopal-Srivastava R, Kaye E, Krischer J, et al. Clinical research for rare disease: opportunities, challenges, and solutions. Mol Genet Metab. 2009;96:20–6. CrossRefPubMed Griggs RC, Batshaw M, Dunkle M, Gopal-Srivastava R, Kaye E, Krischer J, et al. Clinical research for rare disease: opportunities, challenges, and solutions. Mol Genet Metab. 2009;96:20–6. CrossRefPubMed
30.
Zurück zum Zitat Volmar C-H, Brothers S, Wahlestedt C. Development of personalized small molecule modulator screening strategies: upregulation of alpha-L-iduronidase in Mucopolysaccharidosis Type I (MPSI) patient cells. Neuropsychopharmacology. 2012;38:S79–197 (M96). CrossRef Volmar C-H, Brothers S, Wahlestedt C. Development of personalized small molecule modulator screening strategies: upregulation of alpha-L-iduronidase in Mucopolysaccharidosis Type I (MPSI) patient cells. Neuropsychopharmacology. 2012;38:S79–197 (M96). CrossRef
31.
Zurück zum Zitat Avila AM, Burnett BG, Taye AA, Gabanella F, Knight MA, Hartenstein P, et al. Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy. J Clin Invest. 2007;117:659–71. CrossRefPubMedPubMedCentral Avila AM, Burnett BG, Taye AA, Gabanella F, Knight MA, Hartenstein P, et al. Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy. J Clin Invest. 2007;117:659–71. CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat Coles LD, Cloyd JC. The role of academic institutions in the development of drugs for rare and neglected diseases. Clin Pharmacol Ther. 2012;92:193–202. CrossRefPubMed Coles LD, Cloyd JC. The role of academic institutions in the development of drugs for rare and neglected diseases. Clin Pharmacol Ther. 2012;92:193–202. CrossRefPubMed
Metadaten
Titel
Orphan diseases: state of the drug discovery art
verfasst von
PhD Claude-Henry Volmar
MD, PhD Claes Wahlestedt
PhD Shaun P. Brothers
Publikationsdatum
01.06.2017
Verlag
Springer Vienna
Erschienen in
Wiener Medizinische Wochenschrift / Ausgabe 9-10/2017
Print ISSN: 0043-5341
Elektronische ISSN: 1563-258X
DOI
https://doi.org/10.1007/s10354-015-0423-0

Weitere Artikel der Ausgabe 9-10/2017

Wiener Medizinische Wochenschrift 9-10/2017 Zur Ausgabe