FFC#9/2018

Therapeutic potential of a long-acting lung-specific DNase (DNase2b) for the treatment of CF

FFC#9/2018

Therapeutic potential of a long-acting lung-specific DNase (DNase2b) for the treatment of CF

PRINCIPAL INVESTIGATOR

Gianfranco Pasut (Università degli Studi di Padova, Dip. Scienze Farmaceutiche e Farmacologiche)

Partner

Riccardo Percudani (Università degli Studi di Parma, Dip. Scienze Chimiche, della Vita, e della Sostenibilità ambientale)

RESEARCHERS

9

CATEGORY

AREA 1 Therapies to correct the underlying defect

DURATION

2 years

GOAL

€ 40.000 €

RESULTS

The researchers report the results of modification applied to DNAse, already used as a treatment to thin mucus. Human DNAse has been modified through the addition of a polyethylene glycol (PEG) chain generating different conjugates, whose activity has been tested. After optimization of the conjugates synthesis and purification, the efficiency of the modified DNAse was measured with in vitro experiments by evaluating their ability to degrade DNA, thin the artificial mucus and maintain functionality in the presence of the actin, that acts as a natural DNAse inhibitor.
Several human DNAases were considered, including commercially available rhDNAse I (Pulmozyme by Roche), in addition to DNAse2b and DNAse1L2. Among the synthesized and characterized PEGhylated DNAses, DNase1L2 showed good fluidifying capacity on mucus and resistance to actin and the conjugate PEG20kDa-DNase is the most promising in reducing the viscosity of artificial mucus.

OTHER RESULTS

FFC#1/2023

Tezacaftor, one of the components of Kaftrio, induces an accumulation of dihydroceramides both in vitro and in vivo in animal models

FFC#4/2023

Pseudopaline–aztreonam conjugates exhibited enhanced antimicrobial activity against Pseudomonas aeruginosa compared to aztreonam alone

FFC#10/2023

Several drugs already approved for human use inhibit the growth of P. aeruginosa, its virulence, or its ability to form biofilms in vitro