Biomarker-based analysis of preclinical progression in spinal and bulbar muscular atrophy
| Autor: | Takashi Tsuboi, Akihiro Hori, Keisuke Suzuki, Haruhiko Banno, Masahisa Katsuno, Yasuhiro Hijikata, Daisuke Ito, Makoto Hattori, Atsushi Hashizume, Tomonori Inagaki, Shinichiro Yamada, Gen Sobue, Naoki Atsuta, Akihiro Hirakawa |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Weakness Aspartate transaminase Disease Bulbo-Spinal Atrophy X-Linked Kaplan-Meier Estimate Gastroenterology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Trinucleotide Repeats Internal medicine medicine Humans Longitudinal Studies Amyotrophic lateral sclerosis Aged Retrospective Studies Creatinine biology business.industry Amyotrophic Lateral Sclerosis Parkinson Disease Middle Aged medicine.disease Spinal and bulbar muscular atrophy 030104 developmental biology chemistry Alanine transaminase Genetic Techniques Receptors Androgen biology.protein Disease Progression Biomarker (medicine) Female Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | Neurology. 90(17) |
| ISSN: | 1526-632X |
| Popis: | ObjectiveTo identify a candidate biomarker reflecting biological changes during the preclinical progression of spinal and bulbar muscular atrophy (SBMA).MethodsWe analyzed longitudinal changes in biochemical parameters obtained during health examinations before and after the diagnosis of SBMA. We estimated trajectories of clinical markers across years from the onset of weakness using linear mixed models and compared these trajectories with those estimated for male healthy controls and patients with amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD). Moreover, we examined the relationship between serum creatinine level and the onset of symptoms using Kaplan-Meier curves.ResultsBetween October 2014 and October 2017, we enrolled 40 patients with genetically confirmed SBMA, 48 healthy controls, 25 patients with ALS, and 20 patients with PD. In patients with SBMA, we evaluated the patients' data for a period of 17.3 ± 7.5 years, including 11.4 ± 7.1 years of preclinical phase. Decreases in serum creatinine occurred >10 years before the onset. The mean serum creatinine concentration was 0.56 mg/dL at the onset of weakness in patients with SBMA compared to 0.88 ± 0.10 mg/dL on final evaluation in healthy controls. Serum levels of alanine transaminase and aspartate transaminase showed tendencies to increase in preclinical SBMA. These preclinical changes of biomarkers were not observed in either ALS or PD.ConclusionsOur findings suggest that serum creatinine begins to decrease before the onset of clinical symptoms and is a biomarker for disease progression and the efficacy of therapeutics in preclinical SBMA. |
| Databáze: | OpenAIRE |
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