Preclinical pharmacology and safety studies to support an AAV9 NGLY1 gene therapy clinical trial for the treatment of NGLY1 deficiency.

GS-100 is an AAV9 gene replacement therapy for the treatment of N-glycanase 1 (NGLY1) deficiency, an ultra-rare, recessive disorder characterized by developmental delay, intellectual disability, hyperkinetic movement disorder, elevated liver enzymes, (hypo)alacrima, and peripheral neuropathy. In pharmacology studies using rats, intracerebroventricular (i.c.

The STING pathway drives noninflammatory neurodegeneration in NGLY1 deficiency.

The STING pathway is increasingly recognized as a key regulator of neuroinflammation in neurodegenerative disease, but its role in noninflammatory conditions remains unclear. We generated a postnatal inducible whole-body Ngly1 knockout mouse (iNgly1-/-) to model NGLY1 deficiency, an early-onset neurodegenerative disorder. iNgly1-/- mice exhibit progressive motor deficits, Purkinje cell loss, and shortened lifespan without evidence of gliosis or immune activation.

Outcome-associated factors in a molecularly defined cohort of central neurocytoma.

Central neurocytomas (CN) are intraventricular brain tumors predominantly occurring in young adults. Although prognosis is usually favorable, tumor recurrence is common, particularly following subtotal resection (STR). Currently, the risk of progression is evaluated using atypical features and an elevated Ki67 proliferation index.

Advancing CNS tumor diagnostics with expanded DNA methylation-based classification.

DNA methylation-based classification is integral to contemporary neuro-oncological diagnostics, as highlighted by the current World Health Organization (WHO) classification of central nervous system (CNS) tumors. We introduce the Heidelberg CNS Tumor Methylation Classifier version 12.8 (v12.

Predicting memory decline from left temporal lobe epilepsy surgery using preoperative fMRI: a multicenter study.

Objective: While fMRI language laterality has been used to predict verbal memory after epilepsy surgery, supporting evidence is not yet definitive. The FMRI in Anterior Temporal Epilepsy Surgery (FATES) project was a prospective observational cohort study at 10 US epilepsy centers, performed to determine whether a multivariable model including fMRI language laterality can predict verbal memory outcome 6 months after left temporal lobe epilepsy surgery.

Methods: This analysis includes 70 adults who underwent left temporal lobe epilepsy surgeries including hippocampal resection for treatment of epilepsy.