Proof of Concept Grant for Thomas Carell

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Professor Thomas Carell, Chair for Organic Chemistry and member of LMU’s Institute of Chemical Epigenetics – Munich (ICE-M), has been in receipt of a lucrative Advanced Grant from the European Research Council (ERC) since 2016. Now the chemist has been awarded a Proof of Concept Grant to build on this research. With this program, the ERC helps researchers translate their research results into practice.

Thomas Carell investigates why and how the body chemically modifies nucleic acids like DNA and RNA. One such modification is the nucleoside 5-methylcytidine, which is formed by addition of a methyl group to the canonical nucleoside cytidine by enzymes known as methyltransferases. Methylation is important for the regulation of gene activity, but can also be involved in the development of cancer. So-called hypomethylating agents specifically inhibit methyltransferases and are regularly used to treat diseases of the hematopoietic system such as AML (acute myeloid leukemia) and MDS (myelodysplastic syndrome) in older patients whose general state of health is poor.

A promising candidate

However, treatment options are currently constrained by the instability of these agents. Despite research into alternative therapeutic approaches, the need for a mild treatment option with high success rates in this patient population remains unmet. This is where Thomas Carell comes in, who has managed to develop a more stable agent in the form of the compound Carbacitabin (CAB), which demonstrated improved efficacy and reduced toxicity in AML mouse models compared to previous therapeutics. This makes CAB a promising candidate for treating leukemia in high-risk patients.

In his new project leuCAB (Preclinical development of new nucleoside-based drug against leukemia), Carell now wants to take essential preclinical steps toward fully realizing the potential of CAB. This includes further optimization of the structure of the agent and thorough preclinical studies to evaluate the safety and efficacy of CAB. Additionally, the synthesis of CAB is to be scaled up to cover the demand for preclinical and subsequent clinical trials. To carry out clinical studies, Carell plans to establish a spin-off company and will engage with essential stakeholders to this end. “This comprehensive approach will ensure the effective translation of CAB from bench to bedside, bringing new hope to patients, especially those battling AML and MDS,” says Carell.

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