Fabry's disease medical therapy

	Fabry's disease Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Fabry's disease from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
CT
MRI
Echocardiography or Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Fabry's disease medical therapy On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Fabry's disease medical therapy All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Fabry's disease medical therapy
CDC on Fabry's disease medical therapy
Fabry's disease medical therapy in the news
Blogs on Fabry's disease medical therapy
Directions to Hospitals Treating Fabry's disease
Risk calculators and risk factors for Fabry's disease medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ghazal Sanadgol, M.D.[2]

Overview

The mainstay of therapy for Fabry's disease is enzyme replacement by Agalsidases. Other treatment is increasing the enzyme activity by Migalastat. There are also some general treatments for Fabry's disease complications.

Medical Therapy

Specific Treatments

Enzyme replacement therapy (ERT):

Recombinant human enzymes
Indications:
- There are no specific guidelines for the timing of the treatment initiation
- One suggestion:
  - Symptomatic and asymptomatic males (homozygotes)
  - Symptomatic females or atypical males
Drugs:
- Agalsidase alfa (Replagal): 0.2mg/kg IV every two week^[1]^[2]
- Agalsidase beta (Fabrazyme): 1mgl/kg IV every two week^[3]^[4]

Increase the enzyme activity:

Stabilize the mutant form of the alpha-galactosidase enzyme and increase its activity.

Indication: Patient with amenable GLA gene variants
Drug:
- Migalastat: 123mg PO once every other day^[5]^[6]^[7]

Symptom and Complication Treatments

Kidney disease ^[8]

ACE inhibitors and ARBs: can reduce proteinuria and stable GFR in patients with hypertension and Fabry's disease.
Dialysis: in ESRD

Cardiovascular disease

Anti-anginal medications^[9]
Antiarrhythmic medications^[10]
Heart failure Medications^[11]

Neurological disease

Neuropathic pain^[12]
- Reduce by ERT
- Gabapentin
- Anti-convulsant drugs
Reduce the risk of stroke^[13]
- Antiplatelet (primary and secondary prevention)

References

↑ Ramaswami U, Parini R, Pintos-Morell G, Kalkum G, Kampmann C, Beck M; et al. (2012). "Fabry disease in children and response to enzyme replacement therapy: results from the Fabry Outcome Survey". Clin Genet. 81 (5): 485–90. doi:10.1111/j.1399-0004.2011.01671.x. PMID 21457233.
↑ Ries M, Clarke JT, Whybra C, Timmons M, Robinson C, Schlaggar BL; et al. (2006). "Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease". Pediatrics. 118 (3): 924–32. doi:10.1542/peds.2005-2895. PMID 16950982.
↑ Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S; et al. (2001). "Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease". N Engl J Med. 345 (1): 9–16. doi:10.1056/NEJM200107053450102. PMID 11439963.
↑ Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M; et al. (2007). "Agalsidase-beta therapy for advanced Fabry disease: a randomized trial". Ann Intern Med. 146 (2): 77–86. doi:10.7326/0003-4819-146-2-200701160-00148. PMID 17179052.
↑ Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR; et al. (2016). "Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat". N Engl J Med. 375 (6): 545–55. doi:10.1056/NEJMoa1510198. PMID 27509102.
↑ Mauer M, Sokolovskiy A, Barth JA, Castelli JP, Williams HN, Benjamin ER; et al. (2017). "Reduction of podocyte globotriaosylceramide content in adult male patients with Fabry disease with amenable GLA mutations following 6 months of migalastat treatment". J Med Genet. 54 (11): 781–786. doi:10.1136/jmedgenet-2017-104826. PMC 5740534. PMID 28756410.
↑ Germain DP, Nicholls K, Giugliani R, Bichet DG, Hughes DA, Barisoni LM; et al. (2019). "Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study". Genet Med. 21 (9): 1987–1997. doi:10.1038/s41436-019-0451-z. PMC 6752321 Check |pmc= value (help). PMID 30723321.
↑ Wanner C, Breunig F (2007). "Fabry nephropathy and the case for adjunctive renal therapy". J Am Soc Nephrol. 18 (9): 2426–8. doi:10.1681/ASN.2007070783. PMID 17699807.
↑ O'Mahony C, Elliott P (2010). "Anderson-Fabry disease and the heart". Prog Cardiovasc Dis. 52 (4): 326–35. doi:10.1016/j.pcad.2009.11.002. PMID 20109602.
↑ Weidemann F, Maier SK, Störk S, Brunner T, Liu D, Hu K; et al. (2016). "Usefulness of an Implantable Loop Recorder to Detect Clinically Relevant Arrhythmias in Patients With Advanced Fabry Cardiomyopathy". Am J Cardiol. 118 (2): 264–74. doi:10.1016/j.amjcard.2016.04.033. PMID 27265676.
↑ WRITING COMMITTEE MEMBERS. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE; et al. (2013). "2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines". Circulation. 128 (16): e240–327. doi:10.1161/CIR.0b013e31829e8776. PMID 23741058.
↑ Watson JC, Dyck PJ (2015). "Peripheral Neuropathy: A Practical Approach to Diagnosis and Symptom Management". Mayo Clin Proc. 90 (7): 940–51. doi:10.1016/j.mayocp.2015.05.004. PMID 26141332.
↑ Moore DF, Kaneski CR, Askari H, Schiffmann R (2007). "The cerebral vasculopathy of Fabry disease". J Neurol Sci. 257 (1–2): 258–63. doi:10.1016/j.jns.2007.01.053. PMID 17362993.

[pmid21457233-1] Ramaswami U, Parini R, Pintos-Morell G, Kalkum G, Kampmann C, Beck M; et al. (2012). "Fabry disease in children and response to enzyme replacement therapy: results from the Fabry Outcome Survey". Clin Genet. 81 (5): 485–90. doi:10.1111/j.1399-0004.2011.01671.x. PMID 21457233.

[pmid16950982-2] Ries M, Clarke JT, Whybra C, Timmons M, Robinson C, Schlaggar BL; et al. (2006). "Enzyme-replacement therapy with agalsidase alfa in children with Fabry disease". Pediatrics. 118 (3): 924–32. doi:10.1542/peds.2005-2895. PMID 16950982.

[pmid11439963-3] Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S; et al. (2001). "Safety and efficacy of recombinant human alpha-galactosidase A replacement therapy in Fabry's disease". N Engl J Med. 345 (1): 9–16. doi:10.1056/NEJM200107053450102. PMID 11439963.

[pmid17179052-4] Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M; et al. (2007). "Agalsidase-beta therapy for advanced Fabry disease: a randomized trial". Ann Intern Med. 146 (2): 77–86. doi:10.7326/0003-4819-146-2-200701160-00148. PMID 17179052.

[pmid27509102-5] Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR; et al. (2016). "Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat". N Engl J Med. 375 (6): 545–55. doi:10.1056/NEJMoa1510198. PMID 27509102.

[pmid28756410-6] Mauer M, Sokolovskiy A, Barth JA, Castelli JP, Williams HN, Benjamin ER; et al. (2017). "Reduction of podocyte globotriaosylceramide content in adult male patients with Fabry disease with amenable GLA mutations following 6 months of migalastat treatment". J Med Genet. 54 (11): 781–786. doi:10.1136/jmedgenet-2017-104826. PMC 5740534. PMID 28756410.

[pmid30723321-7] Germain DP, Nicholls K, Giugliani R, Bichet DG, Hughes DA, Barisoni LM; et al. (2019). "Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study". Genet Med. 21 (9): 1987–1997. doi:10.1038/s41436-019-0451-z. PMC 6752321 Check |pmc= value (help). PMID 30723321.

[pmid17699807-8] Wanner C, Breunig F (2007). "Fabry nephropathy and the case for adjunctive renal therapy". J Am Soc Nephrol. 18 (9): 2426–8. doi:10.1681/ASN.2007070783. PMID 17699807.

[pmid20109602-9] O'Mahony C, Elliott P (2010). "Anderson-Fabry disease and the heart". Prog Cardiovasc Dis. 52 (4): 326–35. doi:10.1016/j.pcad.2009.11.002. PMID 20109602.

[pmid27265676-10] Weidemann F, Maier SK, Störk S, Brunner T, Liu D, Hu K; et al. (2016). "Usefulness of an Implantable Loop Recorder to Detect Clinically Relevant Arrhythmias in Patients With Advanced Fabry Cardiomyopathy". Am J Cardiol. 118 (2): 264–74. doi:10.1016/j.amjcard.2016.04.033. PMID 27265676.

[pmid23741058-11] WRITING COMMITTEE MEMBERS. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE; et al. (2013). "2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines". Circulation. 128 (16): e240–327. doi:10.1161/CIR.0b013e31829e8776. PMID 23741058.

[pmid26141332-12] Watson JC, Dyck PJ (2015). "Peripheral Neuropathy: A Practical Approach to Diagnosis and Symptom Management". Mayo Clin Proc. 90 (7): 940–51. doi:10.1016/j.mayocp.2015.05.004. PMID 26141332.

[pmid17362993-13] Moore DF, Kaneski CR, Askari H, Schiffmann R (2007). "The cerebral vasculopathy of Fabry disease". J Neurol Sci. 257 (1–2): 258–63. doi:10.1016/j.jns.2007.01.053. PMID 17362993.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]