Background: The antisense oligonucleotide Nusinersen recently became the first approved drug against spinal muscular atrophy (SMA). It was approved for all ages, albeit the clinical trials were conducted exclusively on children. Hence, clinical data on adults being treated with Nusinersen is scarce. In this case series, we report on drug application, organizational demands, and preliminary effects during the first 10 months of treatment with Nusinersen in seven adult patients. Methods: All patients received intrathecal injections with Nusinersen. In cases with severe spinal deformities, we performed computed tomography (CT)-guided applications. We conducted a total of 40 administrations of Nusinersen. We evaluated the patients with motor, pulmonary, and laboratory assessments, and tracked patient-reported outcome. Results: Intrathecal administration of Nusinersen was successful in most patients, even though access to the lumbar intrathecal space in adults with SMA is often challenging. No severe adverse events occurred. Six of the seven patients reported stabilization of motor function or reduction in symptom severity. The changes in the assessed scores did not reach a significant level within this short time period. Conclusions: Treating adult SMA patients with Nusinersen is feasible and most patients consider it beneficial. It demands a complex organizational and interdisciplinary effort. Due to the slowly decreasing motor functions in adult SMA patients, long observation phases for this recently approved treatment are needed to allow conclusions about effectiveness of Nusinersen in adults.
Insufficient binding
selectivity of chemosensors often renders
biorelevant metabolites indistinguishable by the widely used indicator
displacement assay. Array-based chemosensing methods are a common
workaround but require additional effort for synthesizing a chemosensor
library and setting up a sensing array. Moreover, it can be very challenging
to tune the inherent binding preference of macrocyclic systems such
as cucurbit[n]urils (CBn) by synthetic
means. Using a novel cucurbit[7]uril-dye conjugate that undergoes
salt-induced adaptation, we now succeeded in distinguishing 14 bioorganic
analytes from each other through the facile stepwise addition of salts.
The salt-specific concentration-resolved emission provides additional
information about the system at a low synthetic effort. We present
a data-driven approach to translate the human-visible curve differences
into intuitive pairwise difference measures. Ion mobility experiments
combined with density functional theory calculations gave further
insights into the binding mechanism and uncovered an unprecedented
ternary complex geometry for CB7. TThis work introduces the non-selectively
binding, salt-adaptive cucurbit[n]uril system for
sensing applications in biofluids such as urine, saliva, and blood
serum.
Sources of MRI phase contrast include magnetic susceptibility, chemical exchange, and tissue microstructure. The novel DEEPOLE QUASAR method disentangles frequency sources and yields separate maps for magnetic susceptibility and non-susceptibility frequency shifts. In this work, we validated the method in vivo and performed the first quantitative study of non-susceptibility frequency in the human brain. We found substantial non-susceptibility contributions in WM and GM. The quantification of non-susceptibility in the human brain provides new ground for theories on the origins of frequency contrast.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.