Therapeutic Potential of Intracerebroventricular Replacement of Modified Human β-Hexosaminidase B for GM2 Gangliosidosis

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB

Development of Training Games of Physical Posture for People with Developmental Disorders

Abstract—This paper describes two prototypes of training games of physical posture adaptive for people with developmental disorders. Two types of games are developed and their prototypes are produced. One is a game for exercise user’s body posture control. The other is a simulator of holding some object horizontally. Though it is said that ASD people generally have resistance against new, inexperienced items, all of the ASD subjects are interested in the games without refusal. This fact is considered to be an effective utilization of attraction and diffusing potential that games have.

Improvement of Training Games of Physical Posture for People with Developmental Disorders

Abstract—This paper describes improvements for training game of physical posture adaptive for people with developmental disorders, which is developed and already reported by the authors. The Game is a game for exercise user’s body posture control. Though it is said that ASD people generally have resistance against new, inexperienced items, all of the ASD subjects are interested in the games without refusal. This fact is considered to be an effective utilization of attraction and diffusing potential that games have. Through this improvement, the Game has been improved to the level that it can be used in the classes of schools by teachers