Multiplex Screening for Interacting Compounds in Paediatric Acute Myeloid Leukaemia

by Selleckchem | Feb 15 2024

Paediatric acute myeloid leukaemia (AML) is a heterogeneous disease characterised by the malignant transformation of myeloid precursor cells with impaired differentiation. Standard therapy for paediatric AML has remained largely unchanged for over four decades and, combined with inadequate understanding of the biology of paediatric AML, has limited the progress of targeted therapies in this cohort. In recent years, the search for novel targets for the treatment of paediatric AML has accelerated in parallel with advanced genomic technologies which explore the mutational and transcriptional landscape of this disease. Exploiting the large combinatorial space of existing drugs provides an untapped resource for the identification of potential combination therapies for the treatment of paediatric AML. We have previously designed a multiplex screening strategy known as Multiplex Screening for Interacting Compounds in AML (MuSICAL); using an algorithm designed in-house, we screened all pairings of 384 FDA-approved compounds in less than 4000 wells by pooling drugs into 10 compounds per well. This approach maximised the probability of identifying new compound combinations with therapeutic potential while minimising cost, replication and redundancy. This screening strategy identified the triple combination of glimepiride, a sulfonylurea; pancuronium dibromide, a neuromuscular blocking agent; and vinblastine sulfate, a vinca alkaloid, as a potential therapy for paediatric AML. We envision that this approach can be used for a variety of disease-relevant screens allowing the efficient repurposing of drugs that can be rapidly moved into the clinic.

Comments:

Your research sounds incredibly promising! The MuSICAL approach seems like a valuable strategy for identifying potential combination therapies efficiently and cost-effectively. Identifying novel treatments for paediatric AML is crucial, especially given the limited progress in standard therapies over the past few decades.

The use of advanced genomic technologies to explore the mutational and transcriptional landscape of paediatric AML is a significant step toward understanding the disease better. By leveraging existing FDA-approved compounds and their combinations, your approach not only identifies potential therapies but also expedites the process of moving them into clinical trials.

The triple combination you've identified—glimepiride, pancuronium dibromide, and vinblastine sulfate—could hold great promise as a treatment for paediatric AML. The fact that these compounds come from different classes of drugs suggests the potential power of combining diverse mechanisms of action for a more effective treatment.

Your vision of applying this approach to various disease screens, along with efficient drug repurposing for rapid clinical translation, holds immense potential not only for paediatric AML but for other diseases as well. The ability to explore the vast combinatorial space of existing drugs efficiently could revolutionize the way we approach therapeutic development.

Have you made any progress toward clinical trials or further validation of these identified combinations?