A patch made in Italy to treat the deadliest brain tumour

"The tumour cells that the surgeon is forced to leave behind are not a technical failure, but a biological and anatomical limitation".

To overcome this therapeutic obstacle, the NeuroMESH development line was born, coordinated by Riva in Humanitas and now funded with 2.7 million euros over five years by the Fondo Italiano per le Scienze Applicate (FISA) of the Italian Ministry of University and Research, which brings together the clinical and nanotechnological expertise of the Italian Institute of Technology IIT.

The project aims to take a biodegradable polymer film developed by the IIT - called μMESH - from preclinical testing to clinical application.

The approach itself is not new: methods of local administration without having to cross the blood-brain barrier have been experimented with over the past thirty years, including wafers - rigid discs impregnated with chemotherapy placed in the cavity at the end of the procedure - but have failed to substantially change clinical practice. The limitation of wafers is physical, rather than pharmacological: a rigid device does not adapt to the irregularities of brain tissue, leaving insufficient contact zones and uneven release.

μMESH starts with a different architecture: a thin, flexible film with an internal microstructure that conforms to the soft tissue and releases drugs in a controlled manner, over a period of weeks.

The technology has already reached a level of maturity (Technology Readiness Level - TRL 3) close to that required for clinical trials. "μMESH can be loaded with different combinations of chemotherapeutics and immunotherapeutics, releasing them locally," says Paolo Decuzzi, Senior Scientist at IIT and professor of oncology at Stanford, who heads the group that developed the technology. "The goal is to target residual tumour cells without exposing the rest of the body to the systemic toxicity of the drugs." I

IT produces the optimised μMESH configurations, which are tested by third-party clinical centres. In addition to Humanitas, which has a cell bank derived from operated patients, exploited for transplantation in mouse models, Stanford Medicine, the University of California San Francisco (UCSF), Harvard Medical School and MD Anderson Cancer Center in Houston are participating in the project, each with their own preclinical models and protocols. 'At a time when international scientific collaborations are under political pressure, this project demonstrates how Italia and the United States can work together efficiently,' notes Decuzzi.

During the five-year project, μMESH will be validated according to the requirements of the European (EMA), Italian (AIFA) and US (FDA) drug agencies. "We have the possibility to replicate in animal models the entire treatment protocol, including radiotherapy," Riva points out. "Phase 1 clinical trials on patients could start in this timeframe, while for a large-scale application the minimum is ten years." Just as with the experimental pipeline of a new drug, 'it is the patients of the future, and not those of today, that we are trying to help,' he concludes.