Introduction

Down syndrome (DS) is a genetic condition with a very complex clinical picture of which cognitive deficit is a relevant aspect. The increase in life expectancy of people with DS has highlighted other co-morbidities, including a marked risk of developing Alzheimer’s-type dementia (AD) after 40 years of age. At present, there are no drugs approved for the treatment of intellectual disability or AD-type neurodegeneration in DS. The object of the invention is the repurposing of a drug already widely used in clinics (very safe) and proven to be effective in improving both intellectual disability and the development of neurodegeneration in DS.

Technical features

A substance shown to have a dual effect when administered in a mouse model of DS: correction of the known imbalance in the excitatory / inhibitory circuits in the brain, which is associated with a significant improvement in cognitive performance; marked reduction and therefore accumulation of neuropathological markers of Alzheimer’s disease. The activity is expressed through a completely new molecular mechanism that modulates an intracellular signalling pathway known to be involved in synaptic transmission and which is altered in DS due to the triplication of chromosome 21. The alteration of the aforementioned pathway has been observed only at cerebral level and consequently the delivery of the drug at the level of the central nervous system allows a site-specific activity, without promoting side effects / adverse effects at the peripheral level. There are no drugs available for the treatment of intellectual disability and the development of AD-type neurodegeneration in people with DS. Technology validated in relevant environment (TRL 5).

Possible Applications

• Treatment of intellectual disability;
• Development of neurodegeneration in subjects with DS.

Advantages

• Superior to the other molecules tested, specific and limited to the brain;
• Restoration of the balance between the activity of the excitatory and inhibitory circuits in the brain;
• Slowing of the progression of the neurodegenerative process;
• Prevention of AD and improvement of cognitive deficits.