Efficacy of Adeno-Associated Virus Serotype 9-Mediated Gene Therapy for AB-Variant GM2 Gangliosidosis.

GM2 gangliosidoses are a group of neurodegenerative lysosomal storage disorders that are characterized by the accumulation of GM2 gangliosides (GM2), leading to rapid neurological decline and death. The hydrolysis of GM2 requires the specific synthesis, processing, and combination of products of three genes-HEXA, HEXB, and GM2A-within the cell's lysosomes. Mutations in these genes result in Tay-Sachs disease, Sandhoff disease, or AB-variant GM2 gangliosidosis (ABGM2), respectively. ABGM2, the rarest of the three types, is characterized by a mutation in the GM2A gene, which encodes the GM2 activator (GM2A) protein. Being a monogenic disease, gene therapy is a plausible and likely effective method of treatment for ABGM2. This study aimed at assessing the effects of administering a one-time intravenous treatment of single-stranded Adeno-associated virus serotype 9 (ssAAV9)-GM2A viral vector at a dose of 1 × 1014 vector genomes (vg) per kilogram per mouse in an ABGM2 mouse model (Gm2a-/-). ssAAV9-GM2A was administered at 1-day (neonatal) or 6-weeks of age (adult-stage). The results demonstrated that, in comparison to Gm2a-/- mice that received a vehicle injection, the treated mice had reduced GM2 accumulation within the central nervous system and had long-term persistence of vector genomes in the brain and liver. This proof-of-concept study is a step forward towards the development of a clinically therapeutic approach for the treatment of patients with ABGM2.

Reduction of Need for Treatment and Length of Hospital Stay Following Institution of a Neonatal Abstinence Syndrome Rooming-In Program in Ontario, Canada.

PURPOSE: To assess the impact of a rooming-in program for babies at risk of Neonatal Abstinence Syndrome (NAS) in one community hospital centre, in Belleville, Ontario. DESIGN AND METHODS: This retrospective chart review was conducted at Belleville General Hospital. The hospital developed a rooming-in program for newborns at risk of NAS in July 2015. Charts on all infants born to mothers using opioids in the 24 months prior to and after the implementation of our program, who met the inclusion criteria, were examined. RESULTS: The study consisted of 15 babies in the Special Care Nursery (SCN) group and 19 babies in the rooming-in group. Rooming-in is associated with a reduction in the need for treatment with morphine [rooming-in group (1/19, 5.3%), SCN group (14/15, 93.3%), p < 0.01], shorter length of stay in hospital [rooming-in group (days = 5), SCN group (days = 20), p < 0.01], improved exclusive breast and/or breast milk-feeding rates [rooming-in group (17/19,89.5%), SCN group (1/15,6.7%), p < 0.01] and lower total hospital cost [rooming-in group ($6458.00), SCN group ($17,851.00), p < 0.01]. CONCLUSION: Our study demonstrates that rooming-in programs for babies born to mothers using opioids has benefits in terms of quality of care and health care resource utilization. PRACTICAL IMPLICATIONS: These findings show that rooming-in can be successfully implemented in a community hospital.

Battery of Behavioral Tests Assessing General Locomotion, Muscular Strength, and Coordination in Mice.

Behavioral testing is used in pre-clinical trials to assess the phenotypic effects and outcomes that a particular disease or treatment has on the animal's wellbeing and health. There are numerous behavioral tests that may be applied. We selected a test for general locomotion, the open field test (OFT); a test for muscular strength, the mesh test (MT); and a test for coordination, the rotarod test (RR). Testing can be accomplished on a weekly or monthly basis. As a test for general locomotion, the OFT works by objectively monitoring movement parameters while the mouse is in an open field apparatus. The field is generally a 2' x 2' box, and the movements are recorded through laser sensing or through video capture. The mouse is placed in the center of the open field and allowed to move freely for the test. The MT uses the latency for a mouse to fall off an inverted screen as a measure of muscular strength. A mouse is placed on a screen, which is inverted over a clear box, and is timed for their latency to fall. Three trials are performed, with the best of the three trials scored for that day. A score of 60 s is the maximum time a mouse is left inverted. Mice are given a 5-min rest period between mesh test trials. Lastly, an accelerated protocol on the RR assesses motor coordination and endurance. During a trial, a mouse walks on a rotating rod as it increases in speed from 4 rpm to 40 rpm over 5 min. The trial ends when the mouse touches the magnetized pressure sensor upon falling. Each mouse undergoes three trials, and the best trial is scored for that day. This combined behavioral data allows for the global assessment of mobility, coordination, strength, and movement of the test animals. At least two out of the three behavioral testing measures must show improvement for an animal to qualify as having overall improved motor function.