New Drug Could Become First to Treat “Untreatable” Childhood Brain Cancer

Could Also Help Patients With Stone Man Syndrome

A new type of drug targeting a genetic weakness in an untreatable childhood brain cancer could become the first-ever therapy engineered to target the disease.

The prototype treatment could also offer hope for patients with fibrodysplasia ossificans progressive, or stone man syndrome, a rare and devasting disease in which muscles and ligaments become bone.

An international team of scientists led by London’s Institute of Cancer Research, found that the new drug class can kill brain-cancer cells with mutations in the ACVR1 gene and shrink tumors in mice.

The new therapy targets the protein produced by mutated versions of ACVR1, which is found in the deadly diffuse intrinsic pontine glioma (DIPG). The team discovered that ACVR1 mutations occur in a quarter of DIPG cancers. Although relatively rare, DIPG is always fatal.

Mutations of the ACVR1 gene don’t exist in any other forms of cancer, but they do cause the inherited disease stone man syndrome, where damaged muscle turns into bone as it heals.

There are currently no life-extending treatments for DIPG, apart from radiotherapy, which is never curative. Following diagnosis, children are expected to live only nine to 12 months.

In the study, just published in Communications Biology, the team tested 11 prototype drugs with anti-ACVR1 activity on brain-cancer cells grown in the lab. Two prototypes proved especially effective at blocking signals sent out by ACVR1 and killing ACVR1-mutant cells, while having a very limited effect on healthy brain cells.

By transplanting human DIPG tumors into mice, the researchers found that the potential new drugs halted ACVR1 activity, shrunk the tumors, and extended survival by 25% (from 67 to 82 days).

The study shows that ACVR1-mutant cells respond inappropriately to the activin A molecule­­––present in high levels during brain development––ultimately bringing about tumor growth.

Patients with stone man syndrome are believed to experience a similar situation, where high activin A-levels arise during muscle inflammation and inappropriately trigger the formation of bone tissue in people born with ACVR1 mutations.

The company M4K Pharma is now in the process of developing the ACVR1 inhibitor drugs, and clinical trials in children with brain cancer are expected to begin in 2021.

Source: The Institute of Cancer Research, May 9, 2019