Proof of Concept Grant for Thomas Carell

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Professor Thomas Carell, Head of the Institute of Chemical Epigenetics at LMU, has been funded by the European Research Council (ERC) since 2016 with a highly endowed ERC Advanced Grant. The chemist has now been awarded a Proof of Concept Grant to build on this. With this program, the ERC supports researchers in transferring their results from research into practice.

Thomas Carell is researching how and why the organism chemically modifies nucleic acids such as the genetic molecules DNA and RNA. One such modification is the insertion of methyl groups by enzymes known as methyltransferases. Methylation is important for the regulation of gene activity, but it 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 with poor general health.

Promising Candidate

However, treatment options are currently limited due to the instability of these active substances. Despite research into alternative therapeutic approaches, there is therefore a considerable need for mild treatment options with high success rates for this patient group. This is where Carell comes in. With the active substance carbacitabine (CAB), he was able to develop a more stable active substance that showed better efficacy and lower toxicity than previous therapeutic agents in the AML mouse model. CAB is therefore a promising candidate for the treatment of leukemia in high-risk patients.

In his new project leuCAB (Preclinical Development of new nucleoside-based drug against leukemia), Carell now wants to drive forward key preclinical steps in order to exploit the potential of CAB. This includes further optimization of the structure of the active substance and comprehensive preclinical studies to evaluate the safety and efficacy of CAB. In addition, CAB synthesis is to be increased in order to meet the demand for preclinical and clinical studies. In order to conduct clinical trials, Carell intends to drive forward the establishment of a spin-off company and involve various key stakeholders. "This comprehensive approach will ensure the effective translation of CAB from the laboratory to the clinic and give new hope to patients, especially those struggling with AML and MDS," says Carell.