Nome del progetto:
Test attraverso metodiche di immunoistochimica su sezioni di tessuto celebrale – siero pazienti con sospette malattie neufrologiche autoimmuni o paraneoplastiche

Principal Investigator: Dr Bruno Giometto

Inizio progetto – Fine progetto: 15/02/2016 – 14/08/2017

Budget: 40.000 €

Staff: Piera De Gaspari

 

Finanziamenti:

   IRP

Abstract:

a) Background:

THE CLINICAL PROBLEM: it has been estimated that 30-60% of drugs are administered without clinical benefits (1). One reason is that “one drug dose does not fit all” and inter-individual pharmacokinetic variability are at risk for drug interactions, and are not devoid of toxicity. GENERAL CHALLENGES: In the past the use of therapeutic drug monitoring (TDM) in paediatrics was severely limited by the need to take large volumes of blood, required to achieve an adequate analytical sensitivity.

TDM is a cue point for personalized therapy of cancer patients treated with traditional chemotherapeutic agents or with new “targeted” therapeutic agents.
Furthermore, TDM is shortly used in clinical setting due to the complexity of this analysis, which is time consuming, costly and needs dedicated recourses. The possibility to perform TDM in a simple way at the bedside of patients will potentially change the management of antineoplastic treatments: reducing toxic adverse effect, increasing efficacy and ultimately decreasing costs for the National Health Service. Finally, the acquired know-how will give new opportunities for spin off development.

THE NEW TECHNOLOGY APPROACHES: this proposal aims to generate an innovative nanotechnology-based high throughput platform to carry out new strategies for hand-friendly, highly sensitive, and inexpensive drug dosage in cancer patients. We will measure the drug concentration with standard methods and with our innovative tools directly in the blood samples of cancer patients enrolled in clinical trials under Good Clinical Practice procedures. On this ground, an Italian and American multidisciplinary network has been setup to work closely together to shorten the time necessary for the effective transfer of knowledge from the laboratory to the clinical practice.

b) Description of the project.

To reach the goal of our proposal, we have organized the interactive network: research-clinical groups (Agostini group-IRP Proteomics facility -CNR-ISTM, Padova, CRO Aviano, Italy ) and Science & Technology-oriented research groups (Agostini- Tasciotti-IRP, Padova Italy, TMHRI, Houston, TX, USA).

Our working hypothesis is that the availability of new and innovative method for the selection and harvest of low molecular weight compounds such as drug and metabolites can expand the potential of LC-MS/MS and MALDI-TOF analytical approaches. The improvement in term of sensitivity and time analysis using small biological samples size offered by this new devices can improve the application of TDM platforms in clinical setting.

c) Specific aim and expected results.

Our working hypothesis is that a fast, sensitive, inexpensive, multiplexed, real-time TDM would

constitute a device step with a significant impact on cancer therapy allowing:
i) new insights for the personalization of drug dosage and the dose adjustment in real time.
ii) to complete the tests without involving traditional central laboratories, thus improving the effectiveness of the process and decreasing the costs.
iii) nanotechnology offers unprecedented opportunities to exploit new tools for the management of cancer treatment and TDM: increase therapeutic efficacy; 2) decrease side effects; 3) improve drugs approach and the choice of the best therapy.