Abstract

ARTESUNATE RESTORES EXPRESSIVE SPEECH AND IMPROVES COGNITIVE FUNCTION IN A PROFOUNDLY DEAF CHILD WITH DOWN’S SYNDROME FEATURES: LITERATURE REVIEW AND A CASE REPORT

S. E. Oriaifo*, N. Oriaifo, M. O. Oriaifo and I. A. Oriaifo

ABSTRACT

There is a variable penetrance and severity of the resulting pathologies in the chromosomal disorder, John Langdon Down’s syndrome (DS). Down’s syndrome is the commonest human non-inheritable cause of mental disability and congenital malformations. Mitochondrial function including PI3K - Akt activation, which may be altered by the culprit genes such as nuclear receptor interacting protein-I (NRIPI), is essential for tissue patterning and the specification of neuronal fates by morphogens. It is also important for anti-oxidant defence and early embryogenesis of neural crest-derived elements such as the cranio-facial skeleton. Akt activators/mTOR inhibitors/GSK 3β inhibitors also increase nuclear residence of NFATc, opposing the negative effects of DSCRI/DYRKIA-NRIPI overexpression on mitochondrial function. The decreased antioxidant phenotype with resultant telomere attrition in DS is similar to that in Alzheimer’s disease (AD) and Hutchinson-Gilford progeria syndrome. Prospective therapies which include AMPK/PGC-Iα activators are now in the pipeline, not only to enhance learning and memory, but also to combat DS-associated AD. We report here a case of a 12-year-old Nigerian girl with DS features whose profound deafness and cognitive defect were reversed by low-dose artesunate therapy for 6 weeks. Child’s modified WeeFIM rating score improved from 74.60 ± 6.44 to 115.50 ± 8.56. Cognitive rating (MMSE) score improved from 8.30 ±1.24 to 18.45 ±3.22. Present evidence is that the anti-oxidant and AMPK activator, artesunate, deserves further trials in order to delineate its place as one of the important preventive and treatment remedies for DS.

Keywords: Down’s Syndrome, Phenotypic Facets, Culprit Genes, Expressive Speech, Cognition, Artesunate.