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Therapeutic effect of soluble factors of M2 phenotype macrophages in children with language impairments

https://doi.org/10.15789/1563-0625-TEO-2224

Abstract

The aim of the present study was to assess safety and clinical efficacy of inhalation immunotherapy based on intranasal administration of bioactive factors produced by the M2 phenotype macrophages in children with language impairments, as well as to study the effect of inhalation immunotherapy on the cytokine profile in the patients' blood serum. The study was carried out according to the NCT04689282 protocol (www.ClinicalTrials.gov) and included 14 children (9 boys / 5 girls), aged 3 to 8 years, with language impairments associated with perinatal or postnatal CNS lesions of various origin. The children recruited into the study were assessed by a neurologist and speech therapist before the therapy, at the end of the course (1 month), and 6 months later. Serum samples for cytokine analysis were obtained before and 1 month after therapy. The course of intranasal inhalations by the conditioned M2 media (2 ml one time per day for 28-30 days) was safe and well tolerated. None of the 14 treated children had significant adverse reactions and severe undesirable events. Intranasal immunotherapy led to a decrease in the severity of language problems, which manifested by improved speech understanding by 45%; the sensorimotor level of speech, by 51%; word formation skills, by 72%, as well as a twofold increase in general and fine motor skills. In children with signs of autism spectrum disorders, along with a language improvement, a decrease in the severity of autistic symptoms was registered, as evidenced by statistically significant decrease in the CARS score from 42.5 to 38.5 after 1 month, and to 33 points after 6 months (p < 0.05). The clinical effect was revealed rather soon, i.e., within a month after the first procedure, being maintained or intensified during a follow-up for 6 months. At the same time, two-thirds of the children showed a clear clinical improvement, with insignificant effect in the rest of patients. Comparative analysis of the serum cytokine levels in these subgroups showed that children with a pronounced positive response to inhaled immunotherapy differed in the following parameters: (1) initially higher level of VEGF and IGF-1, and (2) decrease the level of TNFα in response to intranasal immunotherapy. In summary, we first tested a fundamentally new approach based on the use of soluble factors from M2-type macrophages and intranasal route of their administration in order to treat the children with severe language impairments, demonstrating safety and obtained preliminary data on effectiveness of such approach.

About the Authors

E. Ya. Shevela
Research Institute of Fundamental and Clinical Immunology
Russian Federation

Ekaterina Ya. Shevela - PhD, MD (Medicine), Leading Research Associate, Laboratory of Cellular Immunotherapy, Institute of Fundamental and Clinical Immunology.

630099, Novosibirsk, Yadrintsevskaya str., 14.

Phone: 7 (383) 236-03-29.

Fax: 7 (383) 222-70-28.


Competing Interests:

No



V. G. Degtyareva
Medical Center “Sineglazka”
Russian Federation

Valentina G. Degtyareva - PhD (Medicine), Clinical Neurologist, Honored Doctor of Russian Federation, Head, Medical Center “Sineglazka”.

Novosibirsk.


Competing Interests:

No



A. V. Sosnovskaya
Medical Center “Sineglazka”
Russian Federation

Anastasiya V. Sosnovskaya - Speech Therapist, Medical Center “Sineglazka”.

Novosibirsk.


Competing Interests:

No



E. V. Voronova
Medical Center “Sineglazka”
Russian Federation

Elena V. Voronova - Functional Diagnostics Physician, Medical Center “Sineglazka”.

Novosibirsk.


Competing Interests:

No



M. Yu. Kafanova
Pediatric City Clinical Hospital No. 1
Russian Federation

Marina Yu. Kafanova - PhD (Medicine), Neurosurgeon, Pediatric City Clinical Hospital No. 1.

Novosibirsk.


Competing Interests:

No



I. M. Rashchupkin
Research Institute of Fundamental and Clinical Immunology
Russian Federation

Ivan M. Rashchupkin - Postgraduate Student, Laboratory of Cellular Immunotherapy, Institute of Fundamental and Clinical Immunology.

Novosibirsk.


Competing Interests:

No



A. A. Ostanin
Research Institute of Fundamental and Clinical Immunology
Russian Federation

Aleksandr A. Ostanin - PhD, MD (Medicine), Professor, Chief Research Associate, Laboratory of Cellular Immunotherapy, Institute of Fundamental and Clinical Immunology.

Novosibirsk.


Competing Interests:

No



E. R. Chernykh
Research Institute of Fundamental and Clinical Immunology
Russian Federation

Elena R. Chernykh - PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Head, Laboratory of Cellular Immunotherapy, Institute of Fundamental and Clinical Immunology.

Novosibirsk.


Competing Interests:

Нет



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Shevela E.Ya., Degtyareva V.G., Sosnovskaya A.V., Voronova E.V., Kafanova M.Yu., Rashchupkin I.M., Ostanin A.A., Chernykh E.R. Therapeutic effect of soluble factors of M2 phenotype macrophages in children with language impairments. Medical Immunology (Russia). 2021;23(5):1137-1150. (In Russ.) https://doi.org/10.15789/1563-0625-TEO-2224

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