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Journal of Neurorestoratology  2018, Vol. 6 Issue (1): 41-47    doi: 10.2147/JN.S158843
Original Research     
Monocyte-derived macrophages for treatment of cerebral palsy: a study of 57 cases
Elena Chernykh1, Ekaterina Shevela1, Marina Kafanova2, Lyudmila Sakhno1, Evgeny Polovnikov2, Alexandr Ostanin1
1Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia
2Department of Neurosurgery, Children’s City Clinical Hospital No 1, Novosibirsk, Russia
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Abstract  Objective:

Cell-based technologies are considered to be a new approach for the treatment of cerebral palsy (CP). Given the potent anti-inflammatory activity and high regenerative potential of M2 macrophages, these cells may be a promising source for cell transplantation. To evaluate the safety and efficacy of autologous M2 macrophages, we performed an open-label, Phase I/II, non-controlled clinical trial in children with severe CP.

Patients and methods:

Fifty-seven children with severe CP, including 33 boys and 24 girls, with a median age of 4 years were enrolled in the study. The patients were treated with intrathecal administration of autologous M2 macrophages. The primary outcome measure was safety, and the secondary outcome measure was functional improvement in neurologic scales, including the 66-item Gross Motor Function Measure test, Peabody Developmental Motor Scale-Fine Motor test, Ashworth scale, Medical Resarch Council scale, and an easy-to-understand unified questionnaire for evaluation of cognitive functions in our modification.

Results:

Intrathecal introduction of M2 cells in a median dose of 11.2×106 did not induce any serious adverse events either related with cell injection or during 5 years of follow-up. After 3 months, the Gross Motor Function Measure score increased from 19±4.5 to 77±7.8, the Peabody Developmental Motor Scale-Fine Motor test score improved from 0.9±0.23 to 4.4±0.51, and the Ashworth score decreased from 3.5±0.11 to 2.5±0.16. The assessment of cognitive functions revealed an increase from 1.22±0.24 to 3.98±0.95, and a reduction of seizure syndrome was registered. In addition, M2 injection was accompanied by an increased production of brain-derived neurotrophic factor (pU=0.015).

Conclusion:

The data obtained suggest that cell therapy based on M2 macrophages is safe, does not induce any severe cell-related reactions or long-term side effects and comorbidities, and is accompanied by significant neurologic improvements in severe CP patients.



Key wordscerebral palsy      clinical study      cell-based therapy      M2 macrophages      neurologic improvement     
Published: 26 June 2018
Corresponding Authors: Ekaterina Shevela   
About author: *These authors contributed equally to this work
Cite this article:

Elena Chernykh, Ekaterina Shevela, Marina Kafanova, Lyudmila Sakhno, Evgeny Polovnikov, Alexandr Ostanin. Monocyte-derived macrophages for treatment of cerebral palsy: a study of 57 cases. Journal of Neurorestoratology, 2018, 6: 41-47.

URL:

http://jnr.tsinghuajournals.com/10.2147/JN.S158843     OR     http://jnr.tsinghuajournals.com/Y2018/V6/I1/41

ParametersMean ± SEM (Me; LQ–UQ)
Age, years4.8±0.33 (4; 3–7)
Boys/girls33/24
Body weight, kg15.6±1.05 (13; 12–17)
CP type?
?Spastic quadriplegia24 (42.1%)
?Double hemiplegia26 (45.6%)
?Athetoid quadriplegia2 (3.5%)
?Mixed quadriplegia5 (8.8%)
GMFCS?
?Level III3 (5.3%)
?Level IV6 (10.5%)
?Level V48 (84.2%)
Seizures29/57 (50.8%)
GMFM19.4±4.47 (0; 0–28)
Ashworth scale3.5±0.11 (4; 3–4)
MRC scale1.28±0.14 (1; 0–2)
Fine motor, PDMS-FM0.9±0.23 (0; 0–0)
Cognition1.22±0.24 (0; 0–2)
Cell number, 10611.6±0.86 (11.2; 5.2–16.2)
Table 1Baseline characteristics of 57 patients
Figure 1The improvement in motor and mental activities in CP patients at 3 months after M2 macrophage treatment.
ScalesBefore M2 introductionAfter M2 introduction
GMFM-6619.4±4.47 (0; 0–28)73±7.8 (64; 8–124)**
Ashworth3.5±0.11 (4; 3–4)2.5±0.16 (2; 1–4)**
MRC1.28±0.14 (1; 0–2)2.5±0.15 (3; 2–3)*
Fine motor activity0.9±0.23 (0; 0–0)4.4±0.51 (3; 0–8)**
Cognition1.22±0.24 (0; 0–2)3.98±0.95 (4; 2.5–5.5)**
Table 2Neurologic examination of CP children (N=57) over a 3-month observation period after M2 macrophage introduction
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