Neurology Central

Experimental drug could target IDH1 mutant gliomas, preclinical study indicates

Findings recently published in Cancer Cell have indicated that experimental cell metabolism altering drugs may be effective in the prevention of tumor growth in mice with mutations in the IDH1 gene. The findings could be relevant for up to a third of gliomas that are affected by this mutation.

The study, which was led by researchers at NYU Langone Medical Center (NY, USA), examined human cancer cells carrying the IDH1 mutations both in vitro and in vivo. Analysis of metabolic components highlighted that nicotinamide adenine dinucleotide (NAD) levels were unusually low in IDH1 mutant tumors.

When NAD levels were further lowered through the administration of Nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, the team discovered that the growth of an IDH1 mutant fibrosarcoma was halted. In mice, the administration of these inhibitors indicated no significant side effects and extended lifespan.

Mechanistically, the decrease in NAD levels resulted in a reduction in the cancer cell’s ability to convert sugars and nutrients into energy, resulting in cell death. Cancer cells without IDH1 mutations did not exhibit low levels of NAD and were therefore unharmed by the NAMPT inhibitors.

“Our study marks the first evidence tying IDH1 cancers, which involve a mutation that affects metabolism, with lower levels of a key cell metabolite NAD,” commented study co-senior investigator Andrew Chi (NYU Langone Medical Center). “Our findings raise the possibility that NAMPT inhibitors might be effective against such tumors, which are impervious to current anticancer drugs.”

Currently no cure exists for IDH1 mutant gliomas, which have low survival rates and are most common in individuals between 20 and 30 years of age. The use of NAMPT inhibitors therefore provides a potentially effective treatment for these cancers.

The team are now evaluating the relationship between IDH1 mutant cancers and drops in NAD levels more fully and in the long term hope to launch clinical trials of NAMPT inhibitors in cancer patients with IDH1 mutations.

Source: NYU Langone Medical Center press release