Most ebook files are in PDF format, so you can easily read them using various software such as Foxit Reader or directly on the Google Chrome browser.
Some ebook files are released by publishers in other formats such as .awz, .mobi, .epub, .fb2, etc. You may need to install specific software to read these formats on mobile/PC, such as Calibre.
Please read the tutorial at this link. https://ebooknice.com/page/post?id=faq
We offer FREE conversion to the popular formats you request; however, this may take some time. Therefore, right after payment, please email us, and we will try to provide the service as quickly as possible.
For some exceptional file formats or broken links (if any), please refrain from opening any disputes. Instead, email us first, and we will try to assist within a maximum of 6 hours.
EbookNice Team
Status:
Available4.4
37 reviewsSUMMARYC9orf72-associated amyotrophic lateral sclerosis (c9ALS) is caused by an intronic G4C2 repeat expansion that leads to toxic RNA transcripts and dipeptide repeat proteins (DPRs). A clinical trial using theantisense oligonucleotide (ASO) BIIB078 to target these transcripts was discontinued after failing to provide clinical benefit. Here, we determine the extent of target engagement in the central nervous system(CNS) and elucidate pharmacodynamic cerebrospinal fluid (CSF) biomarkers following treatment. CSFfrom BIIB078-treated cases showed reduced DPRs and sustained increases in inflammatory biomarkers,including C-C motif chemokine ligand 26 (CCL26). BIIB078 was widely distributed in postmortem CNStissue; however, DPRs and phosphorylated TDP-43 remained abundant. Proteomic signatures inc9ALS spinal cord were not altered with treatment, although a distinct increase in RNase T2 abundancethat correlated with BIIB078 concentration was observed. Thus, despite widespread distribution,BIIB078 did not significantly impact key CNS pathologies, emphasizing the need to identify pharmacodynamic biomarkers that reflect disease-relevant neuropathological changes in response to ASOtherapies.