Dental sealants have been shown to be effective in preventing caries in permanent molars. Targeting schools for sealants based on free and reduced-cost lunch participation has been shown to be ...cost-effective. Estimating the cost, including personnel, portable units, and disposable supplies, to meet the Healthy People 2010 objective for sealants in Colorado was undertaken. This information would be used to provide state policy makers with information to set priorities for oral health prevention strategies. Utilizing data from the Colorado Chopper Topper school-based sealant program, which serves the five-county Metro Denver Area, the average program costs were determined. The Chopper Topper program is estimated to serve 32% of eligible schools and 1,500 children in the target area yearly. In 2002, the prevalence of dental sealants in first permanent molars among third graders in Colorado was determined using a convenience sample of 19 counties and estimating the prevalence of sealants statewide. Twenty-nine percent of third graders were found to have at least one sealant, significantly less than the desired Healthy People 2010 objective and Maternal Child Health National Oral Health performance measure. By analyzing these data, the overall dental utilization rates and restoration sequelae over a lifetime obtained from Delta Dental Plan of Colorado, and the societal costs of lost productivity, the cost savings of averted caries through the expansion of the Chopper Topper Sealant Program, by initiating similar programs throughout the state, was projected. The results indicate that the state could easily be divided into target regions served by teams of dental hygienists who would, in most cases, share portable dental units and serve second-grade children in all 276 eligible elementary schools. If all targeted schools agreed to participate and 85% of children received sealants, the percentage of Colorado third graders with at least one sealant would exceed the Healthy People 2010 objective of 50%.
Sandhoff disease (SD) is a fatal neurodegenerative disease caused by a mutation in the enzyme β-N-acetylhexosaminidase. Children with infantile onset SD develop seizures, loss of motor tone and ...swallowing problems, eventually reaching a vegetative state with death typically by 4years of age. Other symptoms include vertebral gibbus and cardiac abnormalities strikingly similar to those of the mucopolysaccharidoses. Isolated fibroblasts from SD patients have impaired catabolism of glycosaminoglycans (GAGs). To evaluate mucopolysaccharidosis-like features of the feline SD model, we utilized radiography, MRI, echocardiography, histopathology and GAG quantification of both central nervous system and peripheral tissues/fluids. The feline SD model exhibits cardiac valvular and structural abnormalities, skeletal changes and spinal cord compression that are consistent with accumulation of GAGs, but are much less prominent than the severe neurologic disease that defines the humane endpoint (4.5±0.5months). Sixteen weeks after intracranial AAV gene therapy, GAG storage was cleared in the SD cat cerebral cortex and liver, but not in the heart, lung, skeletal muscle, kidney, spleen, pancreas, small intestine, skin, or urine. GAG storage worsens with time and therefore may become a significant source of pathology in humans whose lives are substantially lengthened by gene therapy or other novel treatments for the primary, neurologic disease.
•SD cats exhibit cardiac and bony changes, GAG storage and excretion similar to MPS.•Bony changes are present in growth plate and in bone trabeculae.•Cardiac abnormalities include GAG storage in valves.•Intracranial AAV gene therapy corrects GAG storage in the brain and liver.
The GM2 gangliosidoses, Tay–Sachs disease (TSD) and Sandhoff disease (SD), are progressive neurodegenerative disorders that are caused by a mutation in the enzyme β-N-acetylhexosaminidase (Hex). Due ...to the recent emergence of novel experimental treatments, biomarker development has become particularly relevant in GM2 gangliosidosis as an objective means to measure therapeutic efficacy. Here we describe blood, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), and electrodiagnostic methods for evaluating disease progression in the feline SD model and application of these approaches to assess AAV-mediated gene therapy. SD cats were treated by intracranial injections of the thalami combined with either the deep cerebellar nuclei or a single lateral ventricle using AAVrh8 vectors encoding feline Hex. Significantly altered in untreated SD cats, blood and CSF based biomarkers were largely normalized after AAV gene therapy. Also reduced after treatment were expansion of the lysosomal compartment in peripheral blood mononuclear cells and elevated activity of secondary lysosomal enzymes. MRI changes characteristic of the gangliosidoses were documented in SD cats and normalized after AAV gene therapy. The minimally invasive biomarkers reported herein should be useful to assess disease progression of untreated SD patients and those in future clinical trials.
•Clinically relevant biomarkers objectively evaluate feline Sandhoff disease.•Blood, CSF, liver, MRI and electro-diagnostics are utilized to track disease.•Intracranial AAV mediated gene therapy normalizes many of these objective measures.•Minimally invasive biomarkers will inform future human clinical trials.
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