NEutron Capture-enhanced Treatment of neurotoxic Amyloid aggRegates

ended

NECTAR proposes an alternative and revolutionary strategy to address AD (Alzheimer’s Disease) treatment, suggesting and investigating a therapy based mainly on nuclear physics principles and phenomena, i.e. neutron capture nuclear reactions and structural damage of AD Aβ aggregates induced by ionizing radiations (IRs). AD is the most common cause of dementia. There is no cure and no new FDA medication has been approved since 2002. NECTAR aims to develop, test and prove the feasibility, safety and effectiveness of a Capture-Enhanced Neutron Irradiation of Aβ aggregates exploiting the synergy between an external beam of low energy neutrons which irradiate the whole brain and specifically engineered radiation enhancers capable of increasing the administered dose only in the Aβ aggregate site. NECTAR will develop: 1) biocompatible probes containing Gd/B-enriched molecules able to cross the BBB and target selectively the Aβ aggregates; 2) a detailed modelling, validate by innovative dosimetric measurements, of the secondary radiations set in motion at μm and nm scales and related to: (a) the different types of Aβ aggregates and to their radio-induced structural modifications which further relate to neurotoxicity and biological effects, (b) the macroscopic irradiation of the brain and the compatibility with its tolerance assuming a prolonged, highly fractionated low energy neutron irradiation protocol. NECTAR brings an interdisciplinary network of research teams from 7 academics: UNIPV (neutron irradiation), UNITO (probes preparation and testing), MNEGRI (AD mouse models), SU (cellular effects of IRs at low doses and low dose rates), IRSN (IRs metrology), UKESSEN (AD clinics), UKJ (clinical radiotherapy, including advanced particle radiotherapy) and an innovative start-up Raylab (n-spectrometry and miniaturised dosimeters). The positive completion of NECTAR would open the route for the application of IRs-based treatments to other forms of amyloidosis and proteinopathies