There are more than 7000 known rare diseases today, with an overall prevalence of 3.5-5.9%, which equates to 263-446 million people affected globally. The prevalence of neurological symptoms is estimated at 70%.
In this area, enzyme replacement therapies (ERTs) are emerging as promising therapies and to date, 17 ERTs have been approved for lysosomal storage disorders.
However, the development of these biologic drugs is hampered by biological limitations and formulation difficulties related to their properties. Moreover, one of the major challenges is to achieve their targeted and controlled release in the central nervous system (CNS), overcoming the blood-brain barrier (BBB).
The response to this need today is the use of advanced nanomedicine-based delivery systems (NMed) capable of protecting these biological drugs, promoting their controlled release, and determining specificity of action by overcoming biological barriers that are virtually inaccessible for these types of drugs.
However, despite an established experimental literature, there are still difficulties at various levels for their large-scale production. In parallel with formulation development, it is also necessary to have a fast and efficient flow of certified safety analyses.
N2ERT develops a technology platform for the prototyping of therapeutic protein delivery solutions by means of nanoparticles, designed to protect biological activity and reach the CNS. These will be tested for the restoration of biological function in cellular and animal models of disease, using ERTs approved for rare neurometabolic diseases by lysosomal accumulation as platform pivots.
The alpha-mannosidase and sphingomyelinase enzymes supplied by Chiesi Farmaceutici will be used, producing the new NMeds with FDA/EMA approved materials for human use. These will be tested on cell systems based on primary cultures derived from transgenic mice and patient-derived cells to study efficacy and safety in the GLP (Good Laboratory Practice, TransMed Research company) environment.