Biomaterial Database

Blood-derived biomarkers correlate with clinical progression in Duchenne muscular dystrophy. 2020

Kristin Strandberg, and Burcu Ayoglu, and Andreas Roos, and Mojgan Reza, and Erik Niks, and Mirko Signorelli, and Erik Fasterius, and Fredrik Pontén, and Hanns Lochmüller, and Joana Domingos, and Pierpaolo Ala, and Francesco Muntoni, and Annemieke Aartsma-Rus, and Pietro Spitali, and Peter Nilsson, and Cristina Al-Khalili Szigyarto

Department of Protein Science, School of Chemistry, Biotechnology and Health, KTH-Royal Institute of Technology, Stockholm, Sweden.

BACKGROUND Duchenne Muscular Dystrophy is a severe, incurable disorder caused by mutations in the dystrophin gene. The disease is characterized by decreased muscle function, impaired muscle regeneration and increased inflammation. In a clinical context, muscle deterioration, is evaluated using physical tests and analysis of muscle biopsies, which fail to accurately monitor the disease progression. OBJECTIVE This study aims to confirm and asses the value of blood protein biomarkers as disease progression markers using one of the largest longitudinal collection of samples. METHODS A total of 560 samples, both serum and plasma, collected at three clinical sites are analyzed using a suspension bead array platform to assess 118 proteins targeted by 250 antibodies in microliter amount of samples. RESULTS Nine proteins are confirmed as disease progression biomarkers in both plasma and serum. Abundance of these biomarkers decreases as the disease progresses but follows different trajectories. While carbonic anhydrase 3, microtubule associated protein 4 and collagen type I alpha 1 chain decline rather constantly over time, myosin light chain 3, electron transfer flavoprotein A, troponin T, malate dehydrogenase 2, lactate dehydrogenase B and nestin plateaus in early teens. Electron transfer flavoprotein A, correlates with the outcome of 6-minutes-walking-test whereas malate dehydrogenase 2 together with myosin light chain 3, carbonic anhydrase 3 and nestin correlate with respiratory capacity. CONCLUSIONS Nine biomarkers have been identified that correlate with disease milestones, functional tests and respiratory capacity. Together these biomarkers recapitulate different stages of the disorder that, if validated can improve disease progression monitoring.

UI	MeSH Term	Description	Entries
D008137	Longitudinal Studies	Studies in which variables relating to an individual or group of individuals are assessed over a period of time.	Bogalusa Heart Study,California Teachers Study,Framingham Heart Study,Jackson Heart Study,Longitudinal Survey,Tuskegee Syphilis Study,Bogalusa Heart Studies,California Teachers Studies,Framingham Heart Studies,Heart Studies, Bogalusa,Heart Studies, Framingham,Heart Studies, Jackson,Heart Study, Bogalusa,Heart Study, Framingham,Heart Study, Jackson,Jackson Heart Studies,Longitudinal Study,Longitudinal Surveys,Studies, Bogalusa Heart,Studies, California Teachers,Studies, Jackson Heart,Studies, Longitudinal,Study, Bogalusa Heart,Study, California Teachers,Study, Longitudinal,Survey, Longitudinal,Surveys, Longitudinal,Syphilis Studies, Tuskegee,Syphilis Study, Tuskegee,Teachers Studies, California,Teachers Study, California,Tuskegee Syphilis Studies
D008297	Male		Males
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000090602	Collagen Type I, alpha 1 Chain	A fibrillar collagen found predominantly in BONE and SKIN.	COL1A1 Protein,Collagen Type I, alpha 1 Subunit,Collagen alpha 1 (I),Pro alpha 1 Collagen,Pro-alpha1(I) Collagen,Procollagen alpha1(I),Type I Collagen alpha 1,Protein, COL1A1
D000293	Adolescent	A person 13 to 18 years of age.	Adolescence,Youth,Adolescents,Adolescents, Female,Adolescents, Male,Teenagers,Teens,Adolescent, Female,Adolescent, Male,Female Adolescent,Female Adolescents,Male Adolescent,Male Adolescents,Teen,Teenager,Youths
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D015415	Biomarkers	Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, ENVIRONMENTAL EXPOSURE and its effects, disease diagnosis; METABOLIC PROCESSES; SUBSTANCE ABUSE; PREGNANCY; cell line development; EPIDEMIOLOGIC STUDIES; etc.	Biochemical Markers,Biological Markers,Biomarker,Clinical Markers,Immunologic Markers,Laboratory Markers,Markers, Biochemical,Markers, Biological,Markers, Clinical,Markers, Immunologic,Markers, Laboratory,Markers, Serum,Markers, Surrogate,Markers, Viral,Serum Markers,Surrogate Markers,Viral Markers,Biochemical Marker,Biologic Marker,Biologic Markers,Clinical Marker,Immune Marker,Immune Markers,Immunologic Marker,Laboratory Marker,Marker, Biochemical,Marker, Biological,Marker, Clinical,Marker, Immunologic,Marker, Laboratory,Marker, Serum,Marker, Surrogate,Serum Marker,Surrogate End Point,Surrogate End Points,Surrogate Endpoint,Surrogate Endpoints,Surrogate Marker,Viral Marker,Biological Marker,End Point, Surrogate,End Points, Surrogate,Endpoint, Surrogate,Endpoints, Surrogate,Marker, Biologic,Marker, Immune,Marker, Viral,Markers, Biologic,Markers, Immune
D055815	Young Adult	A person between 19 and 24 years of age.	Adult, Young,Adults, Young,Young Adults
D018450	Disease Progression	The worsening and general progression of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.	Clinical Course,Clinical Progression,Disease Exacerbation,Exacerbation, Disease,Progression, Clinical,Progression, Disease
D020388	Muscular Dystrophy, Duchenne	An X-linked recessive muscle disease caused by an inability to synthesize DYSTROPHIN, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, cardiomyopathy (see MYOCARDIAL DISEASES), and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course. (Adams et al., Principles of Neurology, 6th ed, p1415)	Becker Muscular Dystrophy,Duchenne Muscular Dystrophy,Muscular Dystrophy, Becker,Muscular Dystrophy, Pseudohypertrophic,Becker's Muscular Dystrophy,Cardiomyopathy, Dilated, 3B,Cardiomyopathy, Dilated, X-Linked,Childhood Muscular Dystrophy, Pseudohypertrophic,Childhood Pseudohypertrophic Muscular Dystrophy,Duchenne and Becker Muscular Dystrophy,Duchenne-Becker Muscular Dystrophy,Duchenne-Type Progressive Muscular Dystrophy,Muscular Dystrophy Pseudohypertrophic Progressive, Becker Type,Muscular Dystrophy, Becker Type,Muscular Dystrophy, Childhood, Pseudohypertrophic,Muscular Dystrophy, Duchenne Type,Muscular Dystrophy, Duchenne and Becker Types,Muscular Dystrophy, Pseudohypertrophic Progressive, Becker Type,Muscular Dystrophy, Pseudohypertrophic Progressive, Duchenne Type,Muscular Dystrophy, Pseudohypertrophic, Childhood,Progressive Muscular Dystrophy, Duchenne Type,Pseudohypertrophic Childhood Muscular Dystrophy,Pseudohypertrophic Muscular Dystrophy, Childhood,Duchenne Becker Muscular Dystrophy,Duchenne Type Progressive Muscular Dystrophy,Muscular Dystrophy, Becker's,Muscular Dystrophy, Duchenne-Becker,Pseudohypertrophic Muscular Dystrophy