Introduction

L-Asparaginases are used as first line drugs for paediatric Acute Lymphoblastic Leukaemia (ALL) treatment. Yet they are characterized by high in vivo instability, short half-life and the requirement of several administrations. A new E. coli ASNase variant called N24S which tackles these issues has been patented, thus becoming an alternative treatment to successfully address the current challenges of ALL treatment. Preclinical trials in progress.

Technical features

The patented asparaginase N24S variant has improved characteristics in terms of increased in vivo stability, longer half-life, reduced sensitivity to specific proteases that are over-expressed by resistant leukaemia lymphoblasts, and overcomes drug activity and pharmacokinetics of classical asparaginase.

This characteristics render it an alternative treatment to reduce the number of administrations and to successfully address the current challenges of Acute Lymphatic Leukemia treatment.

The fact that the molecule carries only one point mutation compared to the natural one, maintaining the enzymatic activity unaltered and, indeed, presenting further useful aspects, represents a great advantage that drastically reduces both the time and the costs of its introduction into the clinic. Preclinical trials in progress.

Possible Applications

• First line drugs for paediatric Acute Lymphoblastic Leukaemia;
• Treatment of patients resistant to classical asparaginase therapy;
• Treatment of relapsing patients;
• Potential treatment of solid tumors.

Advantages

• Preserved asparaginase and glutaminase activities;
• Long-term storage stability;
• Improved thermal parameters;
• Outstanding resistance to proteases derived from leukaemia cells.