| Autor: |
Andrés-Benito P; Neurologic Diseases and Neurogenetics Group, Institute of Biomedical Research (IDIBELL), 08907 Barcelona, Spain.; CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, 08907 Barcelona, Spain., Vázquez-Costa JF; Neuromuscular Unit and ERN-NMD Group, Department of Neurology, Hospital Universitario y Politécnico La Fe and IIS La Fe, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 46026 Valencia, Spain.; Department of Medicine, University of Valencia, 46021 Valencia, Spain., Ñungo Garzón NC; Neuromuscular Unit and ERN-NMD Group, Department of Neurology, Hospital Universitario y Politécnico La Fe and IIS La Fe, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 46026 Valencia, Spain., Colomina MJ; Anesthesia and Critical Care Department, Bellvitge University Hospital-University of Barcelona, 08907 Barcelona, Spain., Marco C; Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Department of Neurology, Bellvitge University Hospital, 08907 Barcelona, Spain., González L; Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Department of Neurology, Bellvitge University Hospital, 08907 Barcelona, Spain., Terrafeta C; Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Department of Neurology, Bellvitge University Hospital, 08907 Barcelona, Spain., Domínguez R; Neurologic Diseases and Neurogenetics Group, Institute of Biomedical Research (IDIBELL), 08907 Barcelona, Spain.; CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, 08907 Barcelona, Spain.; Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Department of Neurology, Bellvitge University Hospital, 08907 Barcelona, Spain., Ferrer I; CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, 08907 Barcelona, Spain.; Neuropathology Group, Institute of Biomedical Research (IDIBELL), 08907 Barcelona, Spain.; Department of Pathology and Experimental Therapeutics, University of Barcelona, 08907 Barcelona, Spain., Povedano M; Neurologic Diseases and Neurogenetics Group, Institute of Biomedical Research (IDIBELL), 08907 Barcelona, Spain.; CIBERNED (Network Centre of Biomedical Research of Neurodegenerative Diseases), Institute of Health Carlos III, 08907 Barcelona, Spain.; Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Department of Neurology, Bellvitge University Hospital, 08907 Barcelona, Spain. |
| Abstrakt: |
The objective of this study is to evaluate biomarkers for neurodegenerative disorders in adult SMA patients and their potential for monitoring the response to nusinersen. Biomarkers for neurodegenerative disorders were assessed in plasma and CSF samples obtained from a total of 30 healthy older adult controls and 31 patients with adult SMA type 2 and 3. The samples were collected before and during nusinersen treatment at various time points, approximately at 2, 6, 10, and 22 months. Using ELISA technology, the levels of total tau, pNF-H, NF-L, sAPPβ, Aβ40, Aβ42, and YKL-40 were evaluated in CSF samples. Additionally, plasma samples were used to measure NF-L and total tau levels using SIMOA technology. SMA patients showed improvements in clinical outcomes after nusinersen treatment, which were statistically significant only in walkers, in RULM ( p = 0.04) and HFMSE ( p = 0.05) at 24 months. A reduction in sAPPβ levels was found after nusinersen treatment, but these levels did not correlate with clinical outcomes. Other neurodegeneration biomarkers (NF-L, pNF-H, total tau, YKL-40, Aβ40, and Aβ42) were not found consistently changed with nusinersen treatment. The slow progression rate and mild treatment response of adult SMA types 2 and 3 may not lead to detectable changes in common markers of axonal degradation, inflammation, or neurodegeneration, since it does not involve large pools of damaged neurons as observed in pediatric forms. However, changes in biomarkers associated with the APP processing pathway might be linked to treatment administration. Further studies are warranted to better understand these findings. |
