The aim of this invention is the use of myelin nanovesicles (MyVes) in multiple sclerosis (MS) or in Central Nervous System (CNS) diseases. In particular, MyVes could be relevant for myelin repair and/or drug delivery system to the CNS and/or in the development of immunotolerance.
The extrapolated data provided an estimated annual direct cost per patient of about 20,000 euros. Considering also the indirect costs, this value can increase up to triple according to the severity/disability level of the disease.
To date, the market for drugs for MS has reached exorbitant figures, reaching 500 million euros in 2017 alone in Italy.
The main reference market is, therefore, the pharmaceutical one, and thanks to the convergence between technology and health, and ever-deeper penetration of new treatment models and biological drugs based on cellular, subcellular, and vesicle therapies is expected.
MyVes are obtained with simple, reproducible protocols and with minimal production costs. Furthermore, the vesicles are stable at room temperature. These characteristics make them a potential innovative biotechnological drug with high relevance in the pharmaceutical sector. A further innovation would be the possibility of administering these vesicles by nasal spray.
"Patients would finally have a new therapeutic option available that would represent the first nasal treatment for multiple sclerosis"
The demyelinating diseases form a wide group of pathologies characterized by an impairment of the myelin that covering nerve cells. The demyelinated axons are sensitive to damage, degeneration, and death causing devastating disability. Among these pathologies, the best known is multiple sclerosis (MS), an autoimmune pathology. Recently, vesicles or nanoparticles have been proposed as a valuable tool for drug delivery or as drugs themselves. However, the use of nanocarriers/drug myelin-made is not still present in the medical landscape.
The goal of this study is the production of myelin nanovesicles (MyVes) that can be relevant for myelin repair, as a drug delivery system to the nervous system and for immune tolerance effect. This innovative approach is therefore based on multiple potentials that, in a single or synergistic way, could lead to the identification of an innovative therapeutic approach against demyelinating diseases. In the world, there are more than 2.2 million people with MS. In Italy, there are more than 118 thousand and it affects people aged between 20 and 40 to a greater extent, determining a high socio-economic impact for patients, for families, and for the national health system.
Current Technology Limitations
In recent decades, a better understanding of the mechanisms of relapsing-remitting MS has led to the development of several disease-modifying therapies, through the modulation/suppression of the immune system, without however developing a definitive cure. In contrast, current treatment options for progressive MS remain relatively disappointing. These approaches, while mitigating the aggression to the myelin layer, also inhibit the functions of the immune system, leading to high risk and serious side effects.
Furthermore, treatments aimed at promoting myelin repair and reconstitution (thus preventing subsequent neurodegeneration and disability), or treatments that reprogram the immune system making it tolerant to the presence of myelin, are not yet available.
MyVes represent a new and potential innovative approach since their potential action is based on multiple aspects and therefore could:
replenish the damaged myelin layer by intervening on the damage, restoring lost functions (disability);
make the immune system tolerant to the presence of myelin; be used as a carrier of drugs for the central nervous system.
myelin nanoparticles/vesicles for demyelinating diseases such as MS.
The interest is aimed at pharmaceutical companies, in particular in the nanomedicine sector, in order to develop an innovative biotechnological drug with significant economic implications on a global scale.
Our team is developing several ideas related to a concrete application by developing functional activity tests of MyVes on animal systems by nasal or intravenous administration.
Our Technology and solutions
A protocol for the MyVes production was been developed. MyVes produced, were been characterized, from the chemical-physical point of view, in terms of size (˂100 nm), morphology (spheroidal), zeta potential (-37mV), stability ( > three months), and the presence of a phospholipid bilayer and proteins (20%).
MyVes vesicles have been partially characterized from a biological point of view, in fact they are cytocompatible following administration in neuronal cells and are able to interact with them. Finally, MyVes do not show a cytotoxic or activating effect on microglial cells.
The peptides present in the vesicles may be able to direct the vesicle to the target site (interacting with the proteins exposed in the demyelinated neurons) and / or interact with the immune system and induce immunotolerant responses.
Thanks to their nature and chemical-physical and biological characteristics, we foresee that the Myves can counteract the demyelinating pathologies of the CNS, and we foresee a direct action on the CNS through the intranasal route (nasal spray), less invasive or intravenously crossing the blood brain barrier.
Myelin nano-vesicles could represent a new and innovative valuable tool for effective therapy against MS or other demyelinating diseases,
presenting the following advantages:
reduced production costs;
possible non-invasive administration;
minimal adverse effects due to their biological nature.
While the physico-chemical properties of MYVes have been well characterized, the biological-functional properties have not been well explored. To this end the following steps will be:
to analyze the ability of these vesicles to repair demyelinating areas in the MS mouse model system, where the ability to reduce sclerosis and monitor motor deficits through different routes of administration will be evaluated;
evaluate the possibility of loading MyVes with pharmacological molecules with remyelinating and/or anti-inflammatory effect for brain drug delivery;
analyze the immune tolerance effect of MyVes in MS.
Collaboration with a biotechnology company would be necessary to carry out these phases.
After the experimentation on animal models, the possibility of planning a clinical trial will be evaluated, for this purpose some hospitals could be involved.
MyVes were produced using highly reproducible protocols and are in the medium / advanced phase of physico-chemical and biological characterization. The characteristics found make myelin nanovesicles a suitable potential tool for the biomedical applications for which they were created. Furthermore, the absence of cytotoxicity was tested, although in a preliminary way, by means of tests on neuronal and microglial cell cultures. Given its potential and its applications, the patent filed in Italy could be extended on an international scale.