Nanotechnology and Alzheimer disease

New science for an old problem

ALZHEIMER’S DISEASE (AD) is characterised by progressive memory and cognitive dysfunction, due to an irreversible degeneration of neurons that leads to total loss of autonomy and eventually to death. AD currently affects more than 30 million people worldwide, with a forecast of 60 million by 2050. However, despite the high number of people who suffer from this disease, both therapy and diagnosis of AD are underdeveloped.

Assessing strategies

Concerning therapy, there is no cure for AD. The treatments available only provide symptomatic relief, temporarily improving cognitive function, but are unable to slow the long-term progression of the disorder. To date, scientists have mainly focused on the protein fragment Aß when attempting to create AD treatments. This is because two detectable, abnormal structures in the brain of AD patients – senile plaques and neurofibrillary tangles – are intrinsically tied to Aß. Senile plaques former are deposits of the protein, while neurofibrillary tangles are considered a consequence of neuron exposure to it. Many treatment strategies attempt to remove Aß or use enzymatic machinery to degrade it; however, drugs that appeared promising in animal studies have faced problems and, even failure, in human clinical trials, creating an urgent need to develop stratagems either based on new drugs or on new molecular targets to avert a financially overwhelming public health problem.

Concerning diagnostics, though microscopic changes occur in the brain long before the first signs of memory loss, this condition is currently not detectable. Early diagnostics could allow future treatments to target the disease in its initial stages, before irreversible brain damage or mental decline has occurred. Therefore, research on new strategies for earlier diagnosis is among the most active areas in AD research.

Nanotechnology to the rescue

At the forefront of these new strategies is nanotechnology. In particular, nanoparticles (NPs), engineered tuneable devices with the size in the order of a billionth of a meter, are being considered as a useful alternative to treat and diagnose neurodegenerative diseases. By way of treatment, NPs are intriguing candidates for this purpose because of their potential for multi-functionalisation, enabling them to mimic the physiological mechanisms of transport across the blood-brain barrier (BBB). This barrier is an important physical fence made of cells protecting brain from potential hazardous substances in the blood flow; however, it also prevents the passage of 98 per cent of available neuropharmaceuticals and diagnostics. Scientists have synthesised NPs able to convey conventional pharmaceutics and biologicals, such as genes, siRNa, antibodies or contrast agents, to the brain in vitro and in vivo. As an evolution of this approach, in the project ‘Nanoparticles for Therapy and Diagnosis of Alzheimer Disease – NAD’, our group has synthesised nanoparticles able to cross the BBB to reach and eliminate the Aß burden.

Reaching for remedies

However, this research is not yet enough, because brain delivery from nano-carried drugs does not reach the level required to make NPs a viable solution for pharmacological purposes. New and improved strategies are therefore required. Nanotechnology can significantly contribute to these strategies in several ways. For example, scientists have the possibility to design ‘intelligent’ NPs made of a variety of materials that are simultaneously able to cross the BBB and focus on a specific target. Additionally, with increased efficiency and kinetics of brain targeting, nanotechnology could contribute to in vivo diagnostic imaging of brain diseases such as brain ischaemia, stroke, brain tumours and neuro-inflammation. Finally, a significant contribution is envisaged for in vitro diagnostics through the creation of nano-biosensors with unprecedented sensitivity to detect early biomarkers identifying the subject predestined to evolve to AD.

Article published by professors Massimo Masserini and Francesca Re from the Department of Health Sciences at University Milano-Bicocca, to illuminate the potential for nanomedicine to improve the diagnostics and therapy of Alzheimer’s disease. Article available in the publication ‘International Innovation’