Neuron-targeted gene therapy rescues multiple phenotypes of STXBP1-related disorders in mice and is well tolerated in nonhuman primates.
Authors: Aeran R, Tanenhaus A, Sears SMS, Moerke NJ, Miller A, Artur C, Bouhlal Y, Bove PF, Diaz de Arce AJ, Shimizu S, Le J, Place K, Hoffelt D, Amarlkhagva T, Su J, Chen M, Babineau BA, McLaughlin J, Soe M, Macdonald W, Lin IW, Bole D, Valentine KM, Hallam E, Dhanota P, Liu S, Tan SA, Zhao B, Hosur R, Vila MC, Poda S, Belle A, Tagliatela S
Journal: Molecular therapy : the journal of the American Society of Gene Therapy
mental health
psychology
open access
Abstract
In neurodegenerative diseases with a long-term biological disease continuum such as in multiple sclerosis (MS) and Alzheimer’s dementia (AD), individuals already have ongoing disease-specific pathological changes, before clinical symptoms become evident. This key period corresponds to the presymptomatic phase in the course of neurodegenerative diseases. Although individuals do not have any clinical symptoms during the presymptomatic phase, this disease phase can reliably be evaluated and monitored in vivo by numerous biomarkers. With the use of biomarkers, the identification of neurodegenerative diseases in their presymptomatic phase is the ultimate goal in disease management. It results in early detection and evaluation of often subtle preclinical changes and abnormalities that are underway, forecasting future clinical onset and deterioration, serving as a canary in the coal mine. The evaluation of the presymptomatic phase may also enable better understanding of disease mechanisms, development of new treatment strategies and early intervention to modify the disease course and clinical outcomes. Exploring the influence of age and sex on presymptomatic phases of neurodegenerative diseases may further contribute to better disease management by strategically optimizing and individualizing patient care. Multiple sclerosis is the most common demyelinating disease of the central nervous system (CNS), and women are more frequently affected by MS than men. The current female-to-male ratio is increasing and ranges between 2:1 and 3:1 with a potential contribution of increase in female response to epigenetic and environmental changes.(–) In addition to sex differences in MS risk; disease activity, progression, and disability accumulation also differ between female and male patients.() Similar to sex, age plays a crucial role in MS disease course, impacting many aspects of the disease, including relapse frequency, relapse recovery, progression and disability accumulation.()