Behavioural efficacy of intravenous intracerebroventricular and intranasal enzyme replacement therapy in mouse models of alfa-mannosidosis and metachromatic leukodystrophy, human lysosomal storage disorders.

The first objective is to execute a more in-depth study of the behavioural abnormalities in alfa-mannosidosis mice. The focus will be especially on cognitive and emotional protocols, considering the fact that these types of impairments remained unaltered in previous therapeutic attempts. More elaborate knowledge on which functions are intact/impaired will increase the chance to detect significant benefit from therapeutic approaches and to relate the phenotype to brain region-specific pathologies. Secondly, we intend to evaluate the feasibility of ICV ERT in alfa-mannosidosis mice during this project (Second objective) and examine the behavioural efficacy of this treatment. For this purpose we will make use of continuous enzyme infusion via osmotic miniature pumps. Objective 3 includes the exploration of the benefits of intranasal enzyme administration in the mouse models of alfa-mannosidosis and metachromatic leukodystrophy. The fourth and last objective will include the determination of additional value that could be achieved through combinatory ERT approaches.

Keywords:Intracerebroventricular, Intranasal, Alpha-mannosidosis, metachromatic Leukod, bBhavior, Enzyme replacement therapy

Disciplines:Psychiatry and psychotherapy, Nursing, Other paramedical sciences, Clinical and counselling psychology, Other psychology and cognitive sciences