Fabry disease

A pharmacological chaperone on the horizon

For more than a decade, enzyme replacement therapy represented the only treatment option for patients with Fabry disease. New findings suggest that a pharmacological chaperone can induce renal substrate clearance, decrease left ventricular mass and improve gastrointestinal symptoms in patients with specific mutations in GLA.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Mechanism of action of migalastat.


  1. 1

    Clarke, J. T. Narrative review: Fabry disease. Ann. Intern. Med. 146, 425–433 (2007).

    Article  Google Scholar 

  2. 2

    Mehta, A. et al. Enzyme replacement therapy in Fabry disease: comparison of agalsidase alfa and agalsidase beta. Mol. Genet. Metab. 95, 114–115 (2008).

    CAS  Article  Google Scholar 

  3. 3

    Mehta, A. B. Fabry disease: is there a role for enzyme replacement therapy? J. Intern. Med. 274, 329–330 (2013).

    CAS  Article  Google Scholar 

  4. 4

    Markham, A. Migalastat: first global approval. Drugs 76, 1147–1152 (2016).

    Article  Google Scholar 

  5. 5

    Germain, D. P. et al. Safety and pharmacodynamic effects of a pharmacological chaperone on α-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies. Orphanet J. Rare Dis. 7, 91 (2012).

    Article  Google Scholar 

  6. 6

    Germain, D. P. et al. Treatment of Fabry's disease with the pharmacologic chaperone migalastat. N. Engl. J. Med. 375, 545–555 (2016).

    CAS  Article  Google Scholar 

  7. 7

    Hughes, D. et al. Long-term efficacy and safety of migalastat compared to enzyme replacement therapy in Fabry disease: phase 3 study results. Mol. Genet. Metab. 114, S57 (2015).

    Article  Google Scholar 

  8. 8

    Warnock, D. G. et al. Oral migalastat HCl leads to greater systemic exposure and tissue levels of active α-galactosidase A in Fabry patients when co-administered with infused agalsidase. PLoS ONE 10, e0134341 (2015).

    Article  Google Scholar 

  9. 9

    Lenders, M. et al. Serum-mediated inhibition of enzyme replacement therapy in Fabry disease. J. Am. Soc. Nephrol. 27, 256–264 (2016).

    CAS  Article  Google Scholar 

  10. 10

    Sanchez-Fernandez, E. M., Garcia Fernandez, J. M. & Mellet, C. O. Glycomimetic-based pharmacological chaperones for lysosomal storage disorders: lessons from Gaucher, GM1-gangliosidosis and Fabry diseases. Chem. Commun. 52, 5497–5515 (2016).

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding authors

Correspondence to Martina Gaggl or Gere Sunder-Plassmann.

Ethics declarations

Competing interests

M.G. has received a travel grant from Shire HGT. G.S.-P. has received funding from Amicus, Sanofi-Genzyme, and Shire HGT. G.S.-P. and M.G. are investigators of the ATTRACT trial.

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Gaggl, M., Sunder-Plassmann, G. A pharmacological chaperone on the horizon. Nat Rev Nephrol 12, 653–654 (2016). https://doi.org/10.1038/nrneph.2016.138

Download citation

Further reading


Sign up for the Nature Briefing newsletter for a daily update on COVID-19 science.
Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing