Efficacy Safety of Granulocyte Colony-stimulating Factor Treatment Children and Adolescents With Muscular Dystrophy

Efficacy Safety of Granulocyte Colony-stimulating Factor Treatment Children and Adolescents With Muscular Dystrophy

Efficacy and the Safety of Granulocyte Colony-stimulating Factor Treatment in Children and Adolescents With Muscular Dystrophy: An Open Study

Importance: Currently the gold standard treatment for ambulant patients is corticosteroids. Granulocyte colony-stimulating factor (G-CSF) has been reported to exert the proliferation of satellite cells, the regulation of myoblast proliferation, and the differentiation and promotion of muscle regeneration and repair. Objectives To evaluate the safety and efficacy of G-CSF in children and adolescents with muscular dystrophies Duchenne muscular dystrophy, Becker muscular dystrophy , Fascioscapulohumeral dystrophy. Design, Setting, and Participants: Patients aged 5-15 with diagnosed muscular dystrophies will be included in an open study. Patients wheelchair-bound and and mobile and self-independent can participate in the study. Patients also treated with steroids can participate in this study. Clinical examination and physiotherapeutic and laboratory tests will be perform. G-CSF (5mcg/kg/body/d) is given subcutaneously for five consecutive days during the 1st, 2nd, 3rd. 6th and 12th months. Manual muscle testing (Lovett test) of the upper and lower extremities, isometric force with the hand dynamometer, and the 6MWT (six minute walk test) are measured before and after therapy.

Importance: Currently the gold standard treatment for ambulant patients is corticosteroids. Granulocyte colony-stimulating factor (G-CSF) has been reported to exert the proliferation of satellite cells, the regulation of myoblast proliferation, and the differentiation and promotion of muscle regeneration and repair. Objectives To evaluate the safety and efficacy of G-CSF in children and adolescents with muscular dystrophies Duchenne muscular dystrophy, Becker muscular dystrophy , Fascioscapulohumeral dystrophy. Design, Setting, and Participants: Patients aged 5-15 with diagnosed muscular dystrophies will be included in an open study. Patients wheelchair-bound and and mobile and self-independent can participate in the study. Patients also treated with steroids can participate in this study. Clinical examination and physiotherapeutic and laboratory tests will be perform. G-CSF (5mcg/kg/body/d) is given subcutaneously for five consecutive days during the 1st, 2nd, 3rd. 6th and 12th months. Blood is sampled before G-CSF administration and on the 5th day of each treatment cycle. During each cycle of G-CSF administration physical therapy is also applied. Abdominal ultrasonography with a spleen assessment is performed before and after 7 days of G-CSF administration. Spirometry and electrocardiographic record are also performed. Side effects of G-CSF treatment will be assessed. Manual muscle testing (Lovett test) of the upper and lower extremities, isometric force with the hand dynamometer, and the 6MWT (six minute walk test) are measured before and after therapy. MRI of the gastrocnemius muscles will performed at the beginning and at the end of therapy.

Adverse events will be monitored and scored for severity and related to the Granulocyte Colony-Stimulating Factor administration.

The assessment of muscle strength of the upper and lower limbs by Lovett test. The evaluation isometric force of upper limbs with the hand dynamometer. Distance measurement in a 6-minute walk test (6MWT) by feet or wheelchair,6MWT before and after therapy.

Blood count: Red blood cells 10^6/µL; Hemoglobin g/dl, Leucocytes 10^3/µL, Platelets 10^3/µL; biochemistry CRP - C Reactive Protein - mg/L; creatinine - mg/dL; glucose mg/dL, electrolytes, AST- U/L; ALT - U/L; cholesterol mg/dL; fibrinogen - mg/dL, partial thromboplastin time - sec; prothrombin time - sec, creatine kinase - U/L

Abdominal ultrasonography with a spleen measurement will be done before and after G-CSF administration

Electrocardiographic records wiil ibe done in patients with muscular Dystrophy before and after G-CSF administration.

Inclusion Criteria: Muscular dystrophy - Duchenne muscular dystrophy, Becker muscular dystrophy, Fascioscapulohumeral dystrophy age 5-15 Exclusion Criteria: non- muscular dystrophy age below 5 years age over 15 years

Sienkiewicz D, Kulak W, Paszko-Patej G, Okurowska-Zawada B, Sienkiewicz J, Kulak P. Biochemical Changes in Blood of Patients with Duchenne Muscular Dystrophy Treated with Granulocyte-Colony Stimulating Factor. Biomed Res Int. 2019 Mar 13;2019:4789101. doi: 10.1155/2019/4789101. eCollection 2019.

Sienkiewicz D, Kulak W, Okurowska-Zawada B, Paszko-Patej G, Wojtkowski J, Sochon K, Kalinowska A, Okulczyk K, Sienkiewicz J, McEachern E. Efficacy and the Safety of Granulocyte Colony-Stimulating Factor Treatment in Patients with Muscular Dystrophy: A Non-Randomized Clinical Trial. Front Neurol. 2017 Oct 26;8:566. doi: 10.3389/fneur.2017.00566. eCollection 2017.

Eljaszewicz A, Sienkiewicz D, Grubczak K, Okurowska-Zawada B, Paszko-Patej G, Miklasz P, Singh P, Radzikowska U, Kulak W, Moniuszko M. Effect of Periodic Granulocyte Colony-Stimulating Factor Administration on Endothelial Progenitor Cells and Different Monocyte Subsets in Pediatric Patients with Muscular Dystrophies. Stem Cells Int. 2016;2016:2650849. doi: 10.1155/2016/2650849. Epub 2015 Dec 6.