Crag News

L. Maria Lois obtains a PRODUCTE grant to advance on the lead development of a candidate drug for AML

The CSIC researcher at CRAG L. Maria Lois has recently obtained a 100.000€ PRODUCTE grant for the validation of candidate peptides as novel Acute Myeloid Leukemia (AML) treatments.

AML is type of cancer of the myeloid line of blood cells and is one of the most common types of leukemia in adults. AML constitutes and unmet medical need for elderly patients and for patients with relapsed AML. The standard treatment for AML continues to relay mainly on conventional cytotoxic agents, which show low efficiency and cause serious side effects. Some recent studies, though, have pointed out to a novel target for AML treatment: the inhibition of the SUMO (Small Ubiquitin Modifier) conjugation to proteins (SUMOylation). 

L.M. Lois, an international expert on SUMO activation in general and in plant SUMOylation system in particular, developed a molecular tool to modulate SUMO conjugation in vivo. She proposed a novel molecular target based on the disruption of the very specific protein-protein interactions between SUMO E1-E2 enzymes, which, at the same time, are essential for the conjugation of SUMO to proteins. With this idea, Lois assembled a team of collaborators with experts in AML, structural biology, medical oncology and entrepreneurs to start the SUMOblock project, aimed at providing a disruptive therapy for AML patients. 

The SUMOblock project −which has already received funding from the European Research Council (Proof-of-Concept grant), the Generalitat de Catalunya (Llavor Grant) and “la Caixa” Banking Foundation (CaixaImpulse Grant)− is currently in a technology readiness level (TRL) 3. Lois and her team have already identified two SUMOylation inhibitors candidates (iSUM1 and iSUM2), analysed structure-activity relationship, determined mechanism of action by crystallography and in silico modelling, and obtained preliminary data about their capacity to induced death in cancer cells. With the new PRODUCTE grant, the researchers plan to improve the efficacy of iSUM peptides in vitro and in cell lines through a molecular evolution process and perform preliminary toxicology assays (TRL5). This technical development will be accompanied by key activities for the creation of a spin-off biotech to develop the compounds further in the pre-clinical phase. 

The whole team is enthusiastic about the project. “Our drug candidates represent a disruptive approach in the AML treatment, since they would provide a treatment for patients suffering from any AML type, contrary to what happens with the current targeted treatments based on the inhibition of altered protein/enzyme that is present only in a fraction of AML tumors,” explains L.Maria Lois. 

The project “SUMOblock: lead development in the discovery of novel Acute Myeloide Leukemia treatments” (2018 PROD 00171) is financed by the Knowledge Industry Programme (Modality B: Producte Call), promoted by the Secretariat for Universities and Research of the Government of Catalonia (Ministry of Business and Knowledge). This call is co-funded by the European Union through the European Regional Development Fund (ERDF) in the framework of the ERDF Operational Programme Catalonia 2014-2020.