Current Research

There are currently several options being investigated that aim to target the underlying pathology of Fabry disease. They include:

  • Gene therapy
  • Small molecule approaches

Gene therapy

Gene therapy for Fabry disease is in the early stages of investigation. Research has identified two different approaches:

  • Direct delivery of the α-galactosidase A (α-GAL) gene using modified adenoviral and adeno-associated viral vectors in order to genetically modify the liver, lung, or muscle of the patient and use these organs as internal sources of α-GAL.1, 2
  • Genetic alteration of hematopoietic stem cells from Fabry disease patients to produce α-GAL and restoration of the altered cells to the patient through bone marrow transplantation.3, 4

Both methods have shown potential promise in murine model pre-clinical studies.2, 5

Small molecule approaches

Research has also identified two approaches involving “small molecules”. Both of these require some residual α-galactosidase A (α-GAL) activity to be effective, and could potentially be used in conjunction with either gene therapy or enzyme replacement therapy.

The first approach involves substrate inhibition therapy to reduce cellular synthesis of glycosphingolipids.6 Two potentially promising small molecules are N-butyldeoxynojirimycin and D-threo-1-ethylendioxyphenyl-2-palmitoylamino-3-pyrrolidino-propanol (D-t-EtDO-P4).6, 7

A second approach, commonly referred to as "chaperone therapy", involves use of a competitive inhibitor of α-GAL to increase the activity of residual enzyme. In animal studies, oral administration of small doses of 1-deoxy-galactonojirinmycin increased the transport and maturation of mutant α-GAL, and increased α-GAL activity in some organs.8


1. Ohsugi K, Kobayashi K, Itoh K, Sakuraba H, Sakuragawa N. Enzymatic corrections for cells derived from Fabry disease patients by a recombinant adenovirus vector. J Hum Genet. 2000;45:1-5.

2. Ziegler RJ, Yew NS, Li C, et al. Correction of enzymatic and lysosomal storage defects in Fabry mice by adenovirus-mediated gene transfer. Hum Gene Ther. 1999;10:1667-1682.

3. Takiyama N, Dunigan JT, Vallor MJ, Kase R, Sakuraba H, Barranger JA. Retrovirus-mediated transfer of human α-galactosidase A gene to human CD34+ hematopoietic progenitor cells. Hum Gene Ther. 1999;10:2881-2889.

4. Takenaka T, Hendrickson CS, Tworek DM, et al. Enzymatic and functional correction along with long-term enzyme secretion from transduced bone marrow hematopoietic stem/progenitor and stromal cells derived from patients with Fabry disease. Exp Hematol. 1999;27:1149-1159.

5. Takenaka T, Murray GJ, Qin G, et al. Long-term enzyme correction and lipid reduction in multiple organs of primary and secondary transplanted Fabry mice receiving transduced bone marrow cells. Proc Natl Acad Sci U S A. 2000;97:7515-7520.

6. Platt FM, Butters TD. New therapeutic prospects for the glycosphingolipid lysosomal storage diseases. Biochem Pharmacol. 1998;56:421-430.

7. Abe A, Gregory S, Lee L, et al. Reduction of globotriaosylceramide in Fabry disease mice by substrate deprivation. J Clin Invest. 2000;105:1563-1571.

8. Fan J-Q, Ishi S, Asano N, Suzuki Y. Accelerated transport and maturation of lysosomal α-galactosidase A in Fabry lymphoblasts by an enzyme inhibitor. Nat Med. 1999;5:112-115.