Table 1 Baseline patient demographics and treatment phase outcomes.

From: Lentivirus-mediated gene therapy for Fabry disease

Parameter

Patient 1

Patient 2

Patient 3

Patient 4

Patient 5

Age (years)

48

39

39

37

29

GLA mutation

p.Gln321Arg

p.Ser345Pro

p.Ala143Pro

p.Ala143Pro

p.Tyr134Ser

Age at diagnosis (years)

36

29

0

4

14

Age started ET (years)

36

33

36

26

29

Fabry symptoms at baseline

Acroparesthesia

  

x

  

Angiokeratoma

x

x

 

x

x

Cardiomyopathy

x

 

x

x

 

Chronic kidney disease

 

x

   

Cold intolerance

 

x

   

Corneal verticillata

 

x

x

x

 

Gastrointestinal

x

x

 

x

x

Heat intolerance

 

x

   

Hypertension

   

x

x

Hypohidrosis

 

x

 

x

x

Headaches and migraines

    

x

Pain

   

x

x

Peripheral sensory neuropathy

 

x

   

Proteinuria

x

x

   

Tinnitus or hearing loss

  

x

x

x

Mobilization agents

G-CSF

G-CSF + plerixafor

G-CSF + plerixafor

G-CSF + plerixafor

G-CSF

Apheresis yield CD34+ cells ×106/kg

8.4

9.2

18.1

9.0

5.1

Drug product VCN (copies/genome)

0.68

1.43

0.81

1.37

1.13

Drug product infused: CD34+ cells ×106/kg

4.9

6.4

13.8

6.2

3.1

Colony PCRa

 Mock

0%

0%

0%

ND

ND

 LV-AGA (Drug Product)

52%

62%

54%

ND

ND

 Colony PCR on Day −2 BM samples

ND

0/86 (0%)

0/88 (0%)

0/92 (0%)

0/88 (0%)

 Colony PCR on Day 28 BM samples

10/28 (35.7%)

70/92 (76.1%)

63/90 (70.0%)

52/92 (56.5%)

56/88 (63.6%)

 Actual study day for colony PCR

Day 33

Day 28

Day 28

Day 28

Day 32

Day −2 BM α-gal A nmoles/hr/mg

0.3

1.0

1.6

1.0

0.8

Day 28 BM α-gal A nmoles/hr/mg

220

350

169

320

569

Time to engraftment (absolute neutrophil count >0.5 x 109 cells per L)b

Day 12

Day 13

Day 11

Day 11

Day 12

Time to engraftment (platelet count >20 x 109 per L)

Day 12

Day 12

Day 12

Day 11

Day 12

Day −2 BM VCN copies/genome

0.00

0.00

0.00

0.00

0.00

Day 28 BM VCNc copies/genome

0.47

0.89

0.33

1.10

1.21

Maximum PB VCN copies/genome

0.55

1.10

0.78

0.65

1.30

First Day Plasma α-Gal A activity observed

Day 8d

Day 7

Day 6

Day 6

Day 7

Days from Cell Infusion to ET withdrawal

+548

ND

−41e

+214

ND

  1. BM bone marrow, ET enzyme therapy, ND not done, PB peripheral blood, PCR polymerase chain reaction, VCN vector copy number.
  2. aTransduction efficiency—colony PCR assays.
  3. bRef. 35.
  4. cDay 28–33.
  5. dDefined by activity >2 times the average of pretransplant values.
  6. ePatient 3 discontinued ET prior to infusion and chose not to resume.
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