Emerging therapies in hereditary ataxias.

Recent investigations have defined the pathophysiological basis of many hereditary ataxias (HAs), including loss-of-function as well as gain-of-function mechanisms at either the RNA or protein level. Preclinical studies have assessed gene editing, gene and protein replacement, gene enhancement, and gene knockdown strategies. Methodologies include viral vector delivery of genes, oligonucleotide therapies, cell-penetrating peptides, synthetic transcription factors, and technologies to deliver therapies to defined targets.

A discontinuous Galerkin method for the three-dimensional heterodimer model with application to prion-like proteins' dynamics.

Neurocognitive disorders, such as Alzheimer's and Parkinson's, have a wide social impact. These proteinopathies involve misfolded proteins accumulating into neurotoxic aggregates. Mathematical and computational models describing the prion-like dynamics offer an analytical basis to study the diseases' evolution and a computational framework for exploring potential therapies.

Exploring tau protein and amyloid-beta propagation: a sensitivity analysis of mathematical models based on biological data.

Alzheimer's disease is the most common dementia worldwide. Its pathological development is well known to be connected with the accumulation of two toxic proteins: tau protein and amyloid-$\beta$. Mathematical models and numerical simulations can predict the spreading patterns of misfolded proteins in this context.

B cell focused transient immune suppression protocol for efficient AAV readministration to the liver.

Adeno-associated virus (AAV) vectors are used for correcting multiple genetic disorders. Although the goal is to achieve lifelong correction with a single vector administration, the ability to redose would enable the extension of therapy in cases in which initial gene transfer is insufficient to achieve a lasting cure, episomal vector forms are lost in growing organs of pediatric patients, or transgene expression is diminished over time. However, AAV typically induces potent and long-lasting neutralizing antibodies (NAbs) against capsid that prevents re-administration.