Background
Methods
Protocol approval, patient screening and cell manufacturing
Clinical and neuropsychological assessment
Neuroimaging
Biomechanical evaluation
Cell administration
Results
Case 1 (PSP01) | Case 2 (PSP02) | Case 3 (PSP06) | Case 4 (PSP08) | Case 5 (PSP09) | |
---|---|---|---|---|---|
Demographic data and cell dose | |||||
Gender | M | F | F | F | F |
Age (years) | 60 | 66 | 65 | 65 | 68 |
Disease duration (years) | 8 | 7 | 4 | 6 | 5 |
Cell dose (×106/kg) | 1.4 | 1.7 | 2 | 1.8 | 1.2 |
MMSE | |||||
Baseline | 27.49 | 28.27 | 25.49 | 24.27 | 25.53 |
1-month | 27.49 | 25.27 | 26.49 | 24.27 | 28.53 |
12-month | 26.49 | 25.03 | na | 21.27 | na |
H&Y | |||||
Baseline | 4/5 | 4/5 | 4/5 | 4/5 | 4/5 |
1-month | 4/5 | 4/5 | 4/5 | 4/5 | 4/5 |
3-month | 4/5 | 4/5 | 4/5 | 4/5 | 4/5 |
6-month | 4/5 | 4/5 | na | 4/5 | na |
12-month | 4/5 | 4/5 | na | 4/5 | na |
UPDRS III | |||||
Baseline | 47 | 38 | 47 | 31 | 42 |
1-month | 45 (−4 %) | 37 (−3 %) | 36 (−23 %) | 31 (0 %) | 48 (+14 %) |
3-month | 47 (0 %) | 49 (+29 %) | 48 (+2 %) | 39 (+26 %) | 48 (+14 %) |
6-month | 45 (−4 %) | 51 (+34 %) | na | 40 (+29 %) | na |
12-month | 47 (0 %) | 47 (+24 %) | na | 40 (+29 %) | na |
PSP-RS | |||||
Baseline | 37 | 53 | 52 | 36 | 57 |
1-month | 41 (+11 %) | 40 (−25 %) | 46 (−12 %) | 39 (+8 %) | n.a. |
3-month | 44 (+19 %) | 39 (−26 %) | 43 (−17 %) | 46 (+28 %) | 51 (−11 %) |
6-month | 47 (+27 %) | 63 (+19 %) | na | 52 (+44 %) | na |
12-month | 47 (+27 %) | 57 (+8 %) | na | 53 (+47 %) | na |
Baseline | 12-month | |
---|---|---|
Case 1 (PSP01) | R striatum = 0.16 | R striatum = 0.19 |
L striatum = 0.14 | L striatum = 0.16 | |
R caudate nucleus = 0.27 | R caudate nucleus = 0.10 | |
L caudate nucleus = 0.17 | L caudate nucleus = 0.23 | |
R putamen = 0.08 | R putamen = 0.27 | |
L putamen = 0.10 | L putamen = 0.09 | |
Case 2 (PSP02) | R striatum = 0.49 | R striatum = 0.34 |
L striatum = 0.35 | L striatum = 0.21 | |
R caudate nucleus = 0.59 | R caudate nucleus = 0.48 | |
L caudate nucleus = 0.39 | L caudate nucleus = 0.33 | |
R putamen = 0.42 | R putamen = 0.1 | |
L putamen = 0.35 | L putamen = 0.01 | |
Case 3 (PSP06) | R striatum = 0.42 | na |
L striatum = 0.60 | ||
R caudate nucleus = 0.54 | ||
L caudate nucleus = 0.73 | ||
R putamen = 0.30 | ||
L putamen = 0.43 | ||
Case 4 (PSP08) | R striatum = 1.00 | R striatum = 0.61 |
L striatum = 1.15 | L striatum = 0.72 | |
R caudate nucleus = 1.30 | R caudate nucleus = 0.67 | |
L caudate nucleus = 1.46 | L caudate nucleus = 0.72 | |
R putamen = 0.79 | R putamen = 0.55 | |
L putamen = 0.86 | L putamen = 0.65 | |
Case 5 (PSP09) | R striatum = 0.37 | na |
L striatum = 0.46 | ||
R caudate nucleus = 0.37 | ||
L caudate nucleus = 0.55 | ||
R putamen = 0.36 | ||
L putamen = 0.39 |
(A) | Normal values | Case 1 (PSP01) | Case 4 (PSP08) | ||||
---|---|---|---|---|---|---|---|
(10°–90° percentile) | Basal | 6-month | 12-month | Basal | 6-month | 12-month | |
Standing
| |||||||
Ellipse area (mm2) %BA | 0.06–0.66 | 0.08 | 0.33 | 0.18 | 0.34 | 0.55 | 0.18 |
Ellipse eccentricity | 0.62–0.97 | 0.97 | 0.92 | 0.8 | 0.98 | 0.99 | 0.80 |
Axis length AP avg. (mm) %FL | 0.20–8.86 | 3.05 | 4.21 | 3.35 | 9.27a
| 3.73 | 3.35 |
Axis length ML avg. (mm) %FL | 0.12–3.66 | 2.37 | 2.35 | 1.21 | 0.12 | 1.54 | 1.21 |
Sway path (CoP) velocity avg. (mm/s) | 6.5–18.11 | 7.26 | 7.62 | 6.57 | 9.41 | 19.43 | 6.58 |
Gait initiation
| |||||||
Imbalance phase | |||||||
Duration (s) | 0.29–0.53 | 0.61a
| 0.84a
| 0.49 | 0.36 | 0.43 | 0.36 |
AP avg. (mm) %FL | 9.58–17.26 | 0.86a
| 2.14a
| 1.04a
| 4.48a
| 1.73a
| 0.32a
|
AP vel. avg. (mm/s) | 58.83–112.61 | 3.32a
| 13.68a
| 2.78a
| 22.33a
| 8.31a
| 1.01a
|
ML avg. (mm) %FL | 4.6–19.21 | 5.13 | 6.61 | 3.55a
| 4.12a
| 3.18a
| 3.78a
|
ML vel. avg. (mm/s) | 32.15–144.77 | 17.55a
| 43.53 | 23.1 | 24.78a
| 15.71a
| 27.22a
|
Sway path (CoP) velocity avg. (mm/s) | 96.34–178.07 | 19.38a
| 46.99a
| 26.25a
| 36.17a
| 29.45a
| 28.74a
|
Sway path (CoP) length (mm) | 36.73–63.60 | 14.29a
| 18.75a
| 11.69a
| 16.04a
| 11.12a
| 10.35a
|
Unloading phase | |||||||
Duration (s) | 0.23–0.47 | 1.45a
| 0.83a
| 1.29a
| 1.09a
| 0.76a
| 1.36a
|
AP avg. (mm) %FL | 3.9–14.44 | 7.94 | 8.73 | 8.79 | 11.48 | 12.28 | 8.21 |
AP vel. avg. (mm/s) | 7.1–92.4 | 11.31 | 61.16 | 14.38 | 19.00a
| 37.42 | 10.71 |
ML avg. (mm) %FL | 29.15–61.84 | 33.1 | 43.08 | 36.68 | 54.34 | 45.05 | 37.47 |
ML vel. avg. (mm/s) | 265.14–481.64 | 78.31a
| 143.24a
| 85.81a
| 150.63a
| 151.28a
| 85.31a
|
Sway path (CoP) velocity avg. (mm/s) | 269.18–510.98 | 108.73a
| 150.99a
| 95.58a
| 160.86a
| 163.10a
| 95.63a
|
Sway path (CoP) length (mm) | 79.6–169.24 | 99.07 | 119.54 | 111.61 | 138.33 | 113.69 | 115.61 |
Step phase | |||||||
First step peak velocity (mm/s) | 1475.4–1874.1 | 486.52a
| 783.05a
| 604.83a
| 714.70a
| 498.68a
| 566.64a
|
First step length (%BH) | 26.27–33.63 | 21.04a
| 24.44a
| 17.08a
| 14.34a
| 8.21a
| 16.92a
|
(B) | Normal values | Case 3 (PSP06) | Case 5 (PSP09) |
---|---|---|---|
(10°–90° percentile) | Basal | Basal | |
Standing
| |||
Ellipse area (mm2) %BA | 0.06–0.66 | 0.49 | 329.68a
|
Ellipse eccentricity | 0.62–0.97 | 0.98 | 0.91 |
Axis length AP avg. (mm) %FL | 0.20–8.86 | 6.78 | 5.16 |
Axis length ML avg. (mm) %FL | 0.12–3.66 | 4.31a
| 4.13a
|
Sway path (CoP) velocity avg. (mm/s) | 6.5–18.11 | 133.81a
| 12.69 |
Gait initiation
| |||
Imbalance phase | |||
Duration (s) | 0.29–0.53 | ne | 0.77a
|
AP avg. (mm) %FL | 9.58–17.26 | ne | 6.01 |
AP vel. avg. (mm/s) | 58.83–112.61 | ne | 16.70a
|
ML avg. (mm) %FL | 4.6–19.21 | ne | 5.15 |
ML vel. avg. (mm/s) | 32.15–144.77 | ne | 20.02a
|
Sway path (CoP) velocity avg. (mm/s) | 96.34–178.07 | ne | 31.29a
|
Sway path (CoP) length (mm) | 36.73–63.60 | ne | 22.06a
|
Unloading phase | |||
Duration (s) | 0.23–0.47 | ne | 1.00a
|
AP avg. (mm) %FL | 3.9–14.44 | ne | 5.63 |
AP vel. avg. (mm/s) | 7.1–92.4 | ne | 8.63 |
ML avg. (mm) %FL | 29.15–61.84 | ne | 54.85 |
ML vel. avg. (mm/s) | 265.14–481.64 | ne | 129.37a
|
Sway path (CoP) velocity avg. (mm/s) | 269.18–510.98 | ne | 132.25a
|
Sway path (CoP) length (mm) | 79.6–169.24 | ne | 129.71 |
Step Phase | |||
First step peak velocity (mm/s) | 1475.4–1874.1 | ne | 596.99a
|
First step length (%BH) | 26.27–33.63 | ne | 12.78a
|