To evaluate specific characteristics of phenotype, immune status, molecular and genetic as well as morphological characteristics of adult patients with limb-girdle muscular dystrophy R2 in various regions of the Russian Federation.
A single-center, cohort clinical study. Subjects of both sexes aged 18 to 65 inclusive with genetically confirmed diagnosis of limb-girdle muscular dystrophy type R2, who have signed the written informed consent form for this study. The control and case groups should be age- and gender-matched. Study Objectives: * To evaluate a clinical status of a subject (MMT score; 6-minute walk test; North Star Assessment for dysferlinopathy (NSAD)); * To assess blood biochemistry; * To characterize muscle involvement based on MRI results; * To evaluate the progression of muscle involvement based on repeated MRI; * To assess cardiac function with ECG, EchoCG and MRI; * To determine a gait pattern and balance characteristics in patients with limb-girdle muscular dystrophy using electrophysiological techniques (Neurosoft Gait Assessment System Steadys; stabilometrics and plantography with "SIDAS"); * To characterize changes in subpopulation compositions of T- and B-lymphocytes, phagocytic activity of leukocytes (a phagocytic index, a phagocyte number, an index of phagocytosis completeness, lysosomal-cation and NBT tests); * To assess average blood cytokine levels in subjects with limb-girdle muscular dystrophy (type R2) in various regions of the Russian Federation; * To assess average blood cytokine levels in healthy subjects from various regions of the RF; * To analyze the relationship between blood cytokine levels and the presence of a mutation in the dysferlin gene; * To study the expression (immunohistochemistry and western-blotting) and distribution of dysferlin in impaired muscles of subjects with LGMDR2. The clinical study includes the stages as follows: 1. Subject enrollment - 24 months 2. Data collection and analysis - 12 months 3. Study Report - 30 days.
Study Type
OBSERVATIONAL
Enrollment
100
Human Stem Cells Institute
Moscow, Russia
Сlinical status of patients with dysferlinopathy (MMT score)
Muscle strength will be assessed using MMT and will be expressed in points for each of the muscle groups assessed.
Time frame: Through study completion at 24 months
Сlinical status of patients with dysferlinopathy ( North Star Assessment for dysferlinopathy)
North Star Assessment for Dysferlinopathy (NSAD) is a functional scale that will be used to measure motor performance in individuals with dysferlinopathy (includes 29 items).
Time frame: Through study completion at 24 months
Сlinical status of patients with dysferlinopathy (Hand Held Dynamometry).
Hand held dynamometry using the MicroFET2 myometer will be utilized to capture isometric muscle strength. Maximum strength in kilograms will be reported for each muscle group.
Time frame: Through study completion at 24 months
Сlinical status of patients with dysferlinopathy (6-minute walk test)
The participant will be asked to complete maximal distance in 6 minet as quickly as safely possible and the time in seconds is recorded.
Time frame: Through study completion at 24 months
Clinical blood test (level of hemoglobin)
Level of hemoglobin is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Clinical blood test. Level of hematocrit
Level of hematocrit (%) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Clinical blood test. Level of RBC
Level of RBC is planned to be assessed in patients with dysferlinopathy.
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Time frame: Through study completion at 24 months.
Clinical blood test. Level of WBC
Level of WBC is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Clinical blood test. Levels of ESR
Levels of ESR (mm/h) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Clinical blood test. Level of platelets
Level of platelets is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Biochemical blood test.
Levels of potassium (mmol/l) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months
Biochemical blood test. Level of sodium
Level of sodium (mmol/l) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Biochemical blood test. Level of calcium
Level of calcium (mmol/l) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Biochemical blood test. Level of creatinine
Level of creatinine (μmol/l) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Biochemical blood test. Level of glucose
Level of glucose (mmol/l) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Biochemical blood test. Level of uric acid
Level of uric acid (μmol/l) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Biochemical blood test. Level of urea
Level of urea (mmol/l) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Biochemical blood test. Level of ALT
Level of ALT (U/l) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Biochemical blood test. Level of AST
Level of AST (U/l) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Biochemical blood test. Level of total protein
Level of total protein (g/l) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Biochemical blood test. Level of CPK
Level of CPK (U/l) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Biochemical blood test. Level of triglycerides
Level of triglycerides (mmol/l) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Biochemical blood test. Level of CRP
Level of CRP (mg/l) is planned to be assessed in patients with dysferlinopathy.
Time frame: Through study completion at 24 months.
Blood cytokine levels in subjects with dysferlinopathy and healthy volunteers.
* To assess average blood cytokine levels in subjects with dysferlinopathy in various regions of the Russian Federation; * To assess average blood cytokine levels in healthy subjects. Blood serum cytokine profiling will be performed with the use of the multiparameter fluorescent diagnostic system Luminex 200 and the Bio-Plex Pro Human 27-Plex Panel (Bio-Rad, Hercules, USA) in accordance with the manufacturer's instructions. The data obtained will be processed with the use of MasterPlex CT control and MasterPlex QT analysis software (Hitachi Software, San Bruno, USA). The following cytokine Levels will be assessed in the study:FGF2, Eotaxin,G-CSF, GM-CSF, IFN-γ, IL-1β, 1IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 p70, IL-13, IL-15, IL-17, IP-10, MCP-1/MCAF, MIP-1α, MIP-1β,PDGF-BB, RANTES, TNF-α, VEGF.
Time frame: Through study completion at 24 months
Autoantibodies in patients with dysferlinopathy.
Assessment of antibodу level against skeletal muscle antigens; an antinuclear factor (ANA), an extractable nuclear antigen.
Time frame: Through study completion at 24 months
Muscle MRI in patients with dysferlinopathy.
* To characterize muscle involvement based on MRI results; * To evaluate the progression of muscle involvement based on repeated MRI once year;
Time frame: Through study completion at 24 months.
Subpopulation compositions of T-lymphocytes in subjects with dysferlinopathy.
• To characterize changes in subpopulation compositions of T-lymphocytes in %.
Time frame: Through study completion at 24 months
Subpopulation compositions of B-lymphocytes in subjects with dysferlinopathy.
• To characterize changes in subpopulation compositions of B-lymphocytes in %.
Time frame: Through study completion at 24 months
Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy (NBT test)
• To characterize changes in phagocytic activity of leukocytes (NBT test in CU).
Time frame: Through study completion at 24 months
Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy.
• To characterize changes in phagocytic activity of leukocytes (a phagocyte number in CU).
Time frame: Through study completion at 24 months
Subpopulation compositions of phagocytic activity of leukocytes in subjects with dysferlinopathy (lysosomal-cation test).
• To characterize changes in phagocytic activity of leukocytes (lysosomal-cation test in CU).
Time frame: Through study completion at 24 months
Subpopulation compositions of phagocytic activity of leukocytes (a phagocytic index) in subjects with dysferlinopathy.
• To characterize changes in phagocytic activity of leukocytes (a phagocytic index).
Time frame: Through study completion at 24 months
Gait pattern and balance characteristics in patients with limb-girdle muscular dystrophy R2.
To determine a gait pattern characteristics in patients with limb-girdle muscular dystrophy R2 using electrophysiological techniques (Neurosoft Gait Assessment System "STEDIS").
Time frame: Through study completion at 24 months.
Cardiac function (assessed by Echocardiography). LV
The absolute and relative sizes of the left ventricle (LV) index will be determined.
Time frame: Through study completion at 24 months.
Cardiac function (assessed by Echocardiography). LV mass
The absolute and relative sizes of the LV mass index will be determined.
Time frame: Through study completion at 24 months.
Cardiac function (assessed by Echocardiography). Myocardium mass
The absolute and relative sizes of the myocardium mass index will be determined.
Time frame: Through study completion at 24 months.
Cardiac function (assessed by Echocardiography). RV
The absolute and relative sizes of the right ventricle (RV) index will be determined.
Time frame: Through study completion at 24 months.
Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent). Volumetric evaluation of LV mass
Volumetric evaluation of LV mass by manual tracing will be perform. An MRI of the heart will assess fibrosis.
Time frame: Through study completion at 24 months.
Cardiac function (assessed by Echocardiography). LA
The absolute and relative sizes of the left atrium (LA) index will be determined
Time frame: Through study completion at 24 months.
Cardiac function (assessed by Electrocardiography). Outcome 13
To assess rhythm characteristic, P-wave, QRS, T-wave duration; PR, RR, QT intervals; PR, ST segments.
Time frame: Through study completion at 24 months.
Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent). Volumetric evaluation of EF
Volumetric evaluation of EF by manual tracing will be performed.
Time frame: Through study completion at 24 months.
Cardiac function (assessed by MRI scan with a gadolinium-based contrast agent).
Volumetric evaluation of volume by manual tracing will be performed.
Time frame: Through study completion at 24 months.
Morphological muscle study
If it was necessary to confirm the causation of mutations in the dysferlin gene, the patients underwent muscle biopsy. To study the expression (immunohistochemistry and western-blotting) and distribution of dysferlin in impaired muscles of subjects with LGMDR2.
Time frame: Through study completion at 24 months.