Developing Therapeutic Antibodies for Neurodegenerative Disease

The central nervous system has been considered off-limits to antibody therapeutics. However, recent advances in preclinical and clinical drug development suggest that antibodies can cross the blood–brain barrier in limited quantities and act centrally to mediate their effects. In particular, immunotherapy for Alzheimer’s disease has shown that targeting beta amyloid with antibodies can reduce pathology in both mouse models and the human brain, with strong evidence supporting a central mechanism of action. These findings have fueled substantial efforts to raise antibodies against other central nervous system targets, particularly neurodegenerative targets, such as tau, beta-secretase, and alpha-synuclein. Nevertheless, it is also apparent that antibody penetration across the blood–brain barrier is limited, with an estimated 0.1–0.2 % of circulating antibodies found in brain at steady-state concentrations. Thus, technologies designed to improve antibody uptake in brain are receiving increased attention and are likely going to represent the future of antibody therapy for neurologic diseases, if proven safe and effective. Herein we review briefly the progress and limitations of traditional antibody drug development for neurodegenerative diseases, with a focus on passive immunotherapy. We also take a more in-depth look at new technologies for improved delivery of antibodies to the brain.     

Challenges to recovery following early psychosis: Nursing implications of recovery rate and timing

Early intervention in first episode psychosis is based on an indicated prevention approach that has early illness identification and timely recovery as primary goals. Nurses are instrumental in helping individuals and families achieve both aims. To better understand recovery following a first episode, a prospective cohort of 260 individuals participating in a three-year early intervention program was monitored for achievement of recovery outcomes. Two outcome measures were used to examine the recovery rate and timing of the cohort: (1) partial recovery was comprised of two criteria: (a) symptom control (psychosis and mania), and (b) daily functioning, and 2) comprehensive recovery was measured by three criteria: (a) symptom control; (b) daily functioning; and, (c) quality of life. Survival analysis, including the Kaplan-Meier statistic, and Cox hazard regression were used to examine the cohort's rate and timing for both measures. One hundred and seventy-four individuals attained partial recovery with half (51.1%) reaching the target within nine months. Comprehensive recovery was achieved by 59 individuals (22.7%), primarily in year two and three of treatment. Issues impacting quality of life delayed recovery for the majority of program participants. The gap between psychosis remission and satisfaction/fulfillment with one's everyday life is troubling, but could be improved with stronger nursing support and influence. Sharing the recovery experience with individuals and families that supports their life goals and the discovery of meaning, hope and purpose in the face of illness is the work of nurses. Suggestions for strengthening nursing's impact are considered.     

DSM-5-Based ASD Models: Assessing the Latent Structural Relations with Functionality in War-Exposed Individuals

Psychiatric Quarterly - There is a dearth of studies investigating the latent structure of Acute Stress Disorder (ASD) following the changes in the fifth edition of the Diagnostic and Statistical...