Table 1 Overview of in vitro models of Fabry disease

Q279E

 < 2 nmol/mg/h

Yes (patient fibroblast)

DGJ and galactostatin bisulfide increased α-Gal A activity

[26]

Unknown

Not measured

Yes (patient fibroblast)

Not tested

[38]

Unknown

Not measured

Yes

Clearance of Gb3 deposits upon ERT and influences in pain associated membrane channel

[39]

p.Q280K, p.R342Q, c.801ins36, c.delEx2

 < 0.1 nmol/mg/h

Yes

Clearance of Gb3 deposits upon ERT

[40]

Deletion on exon 3 and 4 on patient cell line, testes plasmids with p.C56Y, p.L300F, p.D244H, p.V269M, p.Q280K, p.A230Tand p.E341D

 < 1 nmol/mg/h

Yes

Acetylsalicylic acid raises α-Gal A activity together with DGJ in amenable mutations

[42]

Unknown

 < 12 nmol/mg/h

Yes (patient fibroblast)

Gene therapy reduced up to 90% of gb3 deposits

[44]

Unknown

Not measured

Induced accumulation

Not tested

[45]

Unknown

Not measured

Induced accumulation

Not tested

[46]

Unknown

Not measured

Induced accumulation

Pentosan polysulfate reduced production of IL-1β and TNF-α

[47]

c.159C > G p.(Asn53Lys), c.400 T > C p.(Tyr134His), c.680G > C (p.Arg227Pro), c.815A > T p.(Asn272Ile), c.907A > T p.(Ile303Phe) and c.1163_1165delTCC (p.Leu388del)

0—53 nmol/mg/h

Yes

Up to 67% rescue with DGJ chaperone

[49]

R112H

 < 20 nmol/mg/h

Yes

Reduction of lysosomal deposits with 24 h of recombinant α-Gal A enzyme

[50]

c.109G > A (p.Ala37Thr, A37T), c.730G > C (p.Asp244His, D244H), c.898C > T (p.Leu300Phe, L300F), c.838C > A (p.Gln280Lys, Q280K), and c.805G > A (p.Val269Met, V269M)

 < 15 nmol/mg/h

Yes

Curcumin treatment increased α-Gal A activity from 1,4 to 2,twofold

[51]

p.N215S and p.L294S

 < 11% of wild type levels

Yes

Increase α-Gal A activity and reduction of Gb3 deposits for p.N215S, but not for p.L294S using DGJ

[52]

c.280 T > C, p.Cys94Arg

40% of wild type levels

Yes

Not tested

[53]

M296I, N263S, G360D, R301Q, D165V, A288D and R100T

0%, 5% and 15% of wild type levels

Not checked

Not tested

[54]

Frame shift from exon 1

0% of wild type (HEK model)

Yes (patient fibroblast)

Proteasome inhibitor increased rhα-Gal A by twofold and 30% increase of Gb3 clearance in patient fibroblasts

[55]

c.898C > T p.L300F; c.838C > A, p.Q280K; c.730G > C, p.D244H; c.902G > C, p.R301P

10% of wild type in L300F

Not mentioned

DGJ helps to stabilize enzyme in different pHs

[56]

None

Not checked

Induced accumulation

High concentrations of DGL to inhibit function

[57]

Not specified

Not checked

Yes (patient cells)

ERT reduced Gb3 accumulation in patient cells

[58]

None

70–80% reduction upon cloroquine treatment

Yes

Not tested

[59]

Disruption of exon 1

Not detectable on knock down or knock-out model

Not mentioned

α-Gal A and eliglustat did not significantly decreased vWF

[60]

Unknown

Less than 2% of wild type

Yes (lyso-gb3)

Improvement of glycocalyx thickness upon ERT or migalastat

[61]

None, GLA shRNA knockdown

45% and 15% of control

Yes

Not tested

[63]

None, GLA shRNA knockdown

Around 4% of control

Yes

Clearance of Gb3 deposits upon ERT combined with DGJ, but not reversal of other signaling disturbances

[64]

Insertion/deletion on exon 1

Less than 2% of wild type

Yes

ERT reverses Gb3 deposits, but not cellular injury

[65]

None, GLA siRNA knockdown

Not directly measured

Not mentioned

Not tested

[66]

None, gla shRNA knockdown

 < 30% of control

Yes

Not tested

[67]

W162X

Not measured

Yes

Not tested

[70]

c.959A > T

Not measured

Yes

Not tested

[71]

IVS4 + 919G > A

 < 20 µg/mg/h (cardiomyocytes)

Yes

Early α-Gal A administration reduced cardiomyocyte hypertrophy

[72]

c.803_806del, p.L268fs*1; c.658C > T, p.Arg220*; c.334C > T, p.Arg112Cys; c.1045 T > C, p.Trp349Arg

 < 1 µmol/mg/h

Yes

aberrant angiogenic function even upon α-Gal A

[73]

Corrected IVS4 + 919G > A

Restored to wild type levels

No

Gene correction led to functional enzyme

[74]

Deletion on exon 1

Not measured

Yes

Glutathione treatment reduced oxidative stress in Fabry kidney organoids, ERT does not fully reverse damage

[75]

c.779G > C

 < 5 nmol/mg/h on mutant and > 15 on normal clone

Yes

Not tested

[76]

IVS4 + 919G > A

 < 10 nmol/mg/h

Yes

ERT led to Gb3 clearance but did not rescue energy metabolism

[77]

c.485G > A, W162X; c.658C > T, R220X

Not detectable

Yes

Treatment with glucosylceramide synthase prevent accumulation and cleared gb3 deposits

[78]

IVS4 + 919G > A

 < 1 µmol/µg/h

Yes

Lower lyso-Gb3 levels and reduction in cardiomyocyte size, potentiated by IL-18 neutralizing antibody

[79]

c.458G > A and c.658C > T

 < 1% of wild type

Yes

Not tested

[80]

c1096C > T, c.568delG, c.708G > C

 < 0.6 nmol/mg/h in all lines

Yes

Gb3 deposits were cleaved up to 27% upon 24h α-Gal A treatment

[81]

Exon 1 deletion

Not detectable

Yes

Not tested

[85]

IVS4 + 919G > A

 < 10 nmol/mg/h

Yes

Non-viral gene correction

[86]

c.969delC, p.Leu324Trpfs ∗ 24; c.263A > G, p.Tyr88Cys

4,6 × 10^3 and 4,9 × 10^4 pmol/mg/h

Yes

not tested

[89]

c.901C > T, p.Arg301X*

Knock out: 3,9 × 10^3; GLA and A4GALT-KO: 1,6 × 10^4; fabry patient 6,2 × 10^3; fabry patient with A4GALT lnock out: 5,9 × 10^3

Yes (fabry patient line and knock-out)

Suppression of A4GALT decreased Gb3 accumulation

[91]