COGNITIVE AND LINGUISTIC FACTORS OF READING ARABIC: THE ROLE OF MORPHOLOGICAL AWARENESS IN READING

Scientific reading research has produced substantial evidence linking specific reading components to a range of constructs including phonological awareness (PA), morphological awareness, orthographic processing (OP), rapid automatized naming, working memory and vocabulary. There is a paucity of research on Arabic, although 420 million people around the world (Gordon, 2005) speak Arabic. As a Semitic language, Arabic differs in many ways from Indo-European languages. Over the past three decades, literacy research has begun to elucidate the importance of morphological awareness (MA) in reading. Morphology is a salient aspect of Arabic word structure. This study was designed to (a) examine the dimensions underlying MA in Arabic; (b) determine how well MA predicts reading; (c) investigate the role of the standard predictors in different reading outcomes; and (d) investigate the construct of reading in Arabic. This study was undertaken in two phases. In Phase I, 10 MA measures and two reading measures were developed, and tested in a sample of 102 Grade 3 Arabic-speaking children. Factor analysis of the 10 MA tasks yielded one predominant factor supporting the construct validity of MA in Arabic. Hierarchical regression analyses, controlling for age and gender, indicated that the MA factor solution accounted for 41– 43% of the variance in reading. In Phase II, the widely studied predictor measures were developed for PA and OP in addition to one additional measure of MA (root awareness), and three reading measures In Phase II, all measures were administered to another sample of 201 Grade 3 Arabic-speaking children. The construct of reading in Arabic was examined using factor analysis. The joint and unique effects of all standard predictors were examined using different sets of hierarchical regression analyses. Results of Phase II showed that: (a) all five reading measures loaded on one factor; (b) MA consistently accounted for unique variance in reading, particularly in comprehension, above and beyond the standard predictors; and (c) the standard predictors had differential contributions. These findings underscore the contribution of MA to all components of Arabic reading. The need for more emphasis on including morphology in Arabic reading instruction and assessment is discussed.

Enhancement of a novel gene therapy approach for Sandhoff disease through complimentary drug therapy

GM2 gangliosidoses is a family of severe, neurodegenerative disorders resulting from a deficiency in the β-hexosaminidase A (Hex A) enzyme. This disorder is typically caused by a mutation to either the HEXA gene, causing Tay Sachs disease, or a mutation to the HEXB gene, causing Sandhoff disease. The HEXA and HEXB genes are required to produce the α and β subunits of the Hex A enzyme respectively. Using a Sandhoff disease (SD) mouse model (Hexb-/-) we tested the potential of a low dose of systemically delivered single stranded adeno-associated virus 9 (ssAAV9) expressing human HEXB and human HEXA cDNA under the control of a single promoter through the use of a bicistronic vector design with a P2A linker to correct the neurological phenotype. Neonatal mice were injected with either this ssAAV9-HexB-P2A-HexA vector (HexB-HexA) or a vehicle solution via the superficial temporal vein. HexB-HexA treatment alone conferred an increase in survival of 56% compared to vehicle-injected controls and biochemical analysis of the brain tissue and serum revealed an increase in HexA activity and a decrease in brain GM2 ganglioside buildup. Additionally, treatments with the non-steroidal anti-inflammatory drug indomethacin (Indo), the histone deactylase inhibitor ITF2357 (ITF) and the pharmacological chaperone pyrimethamine (Pyr) were tested. The anti-inflammatory treatments of Indo and ITF conferred an increase in survival of 12% and 8% respectively while causing no alteration in the HexA activity or GM2 ganglioside buildup. Pyr had no observable effect on disease progression. Lastly HexB-HexA treatment was tested in conjunction with Indo, ITF and Pyr individually. Additive increases in survival and behavioural testing results were observed with Indo and ITF treatments while no additional benefit to HexA activity or GM2 ganglioside levels in the brain tissue was observed. This indicates the two treatments slowed the progression of the disease through a different mechanism than the reduction of the GM2 ganglioside substrate. Pyr treatment was shown to have no effect when combined with HexB-HexA treatment. This study demonstrates the potential amelioration of SD with a novel AAV9 gene therapy approach as well as helped to identify the additive potential of anti-inflammatory treatments in gene therapy of GM2 gangliosidoses.