Biomedical subjects

Carolyn M Tyler

Publications and source records attributed to Carolyn M Tyler.

3 recordsLinked to original sources

PubMed2006

HSV amplicons: neuro applications.

Strategies that employ HSV amplicon vectors in the prevention and/or amelioration of pathogenic states afflicting the central nervous system (CNS) have been extensively documented in preclinical disease models. The versatility of the HSV amplicon platform allows for the implementation of therapeutic approaches that require expression of genes exhibiting neuroprotective or neuroplastic activities, or even applications that necessitate the elaboration of antigen-specific immune responses to pathogenic proteins/structures harbored within the CNS. This discourse highlights the successes and challenges encountered using HSV amplicon vectors as tools for the dissection of neural network function and as therapeutics directed against a variety of neurologic disorders.

Animals↗

PubMed2006

CNS gene therapy and a nexus of complexity: systems and biology at a crossroads.

Gene therapy is a potentially promising new treatment for neurodegenerative disorders such as Alzheimer's disease (AD), which has been difficult to treat with conventional therapeutics. Viral vector-mediated somatic gene therapy is a rapidly developing methodology for providing never before achieved capability to deliver specific genes to the CNS in a highly localized and controlled manner. With the advent and refinements of this technology one focus is directed to which genes are the most appropriate to select for specific disease indications. Nerve growth factor (NGF), a potent survival factor for critical cell populations that degenerate in AD, has been chosen already for clinical gene therapy trials in human AD patients. Much knowledge about the pathophysiological underpinnings of AD is still lacking to make clear which patients may benefit from a gene therapy approach. Moreover, a detailed understanding of sustained NGF action in the normal and diseased CNS needs to be resolved before conclusions can be drawn regarding the utility of NGF gene therapy. Systematic efforts to acquire this new knowledge should compel clinically and biologically sophisticated efforts to advance gene therapy for neurodegenerative diseases.

Alzheimer Disease↗

PubMed2003

Cognitive fatigue during a test requiring sustained attention: a pilot study.

BACKGROUND: Fatigue is common in multiple sclerosis (MS), but difficulty quantifying fatigue severity has impeded studies of its characteristics, mechanisms, and therapeutics. Motor fatigue can be objectively measured as the decline in strength occurring during sustained contractions. Analogous declines in cognitive performance occur during tasks requiring sustained attention. OBJECTIVE: To objectively measure cognitive fatigue as a decline in performance during tests requiring sustained attention. DESIGN/METHODS: Patients with clinically stable MS (n = 20) and healthy controls (n = 21) with comparable age, gender, and education completed the Paced Auditory Serial Addition Test (PASAT) and the Digit Ordering Test (DOT) at two identical test sessions separated by 4-10 days, within a month after two practice sessions. Cognitive fatigue was quantified with two pre-specified methods for each test. The reliability of cognitive fatigue assessments was evaluated with intraclass correlation coefficients (ICCs) and construct validity was evaluated using correlations with measures of self-reported fatigue, cognition, and overall impairment/disability. RESULTS: MS patients had an average of 18.7 items correct on the first 20 items of the PASATand 17.8 correct on the last 20 items, quantified as 5.3-5.8% declines in performance using the different measurement methods (P = 0.01, rejecting the null hypothesis of zero mean decline). Although MS patients as a group demonstrated a similar decline at both sessions, ICCs were relatively low. Control patients did not demonstrate significant declines in performance during PASAT administration, but tests comparing declines in MS patients and controls did not demonstrate significant differences. Fatigue was not demonstrated using the DOT, and test-retest reliability was very poor. CONCLUSIONS: MS patients have objectively measurable cognitive fatigue during administration of the PASAT.

Adolescent↗