Regeneron Discovers GPR75 Gene Mutations Can Protect Against Obesity, Begins Search For New Drugs

  • A team at Regeneron Pharmaceuticals Inc's REGN Genetics Center has discovered mutations in the gene GPR75 that protect against obesity.
  • Now, drug developers at Regeneron will use its VelocImmune technology, which generates antibodies from humanized mice, to find drugs that can mimic the protective properties of the GPR75 variants.
  • Regeneron's researchers started by sequencing the exomes (protein-coding regions of genomes) from around 650,000 people.
  • As reported in Science, the Regeneron team found 16 genes strongly associated with body mass index (BMI). 
  • Five of those encode G protein-coupled receptors (GPCRs) are expressed in the brain and central nervous system.
  • Of the five, GPR75 had the most significant effect on protection against obesity. 
  • People with at least one inactive copy of GPR75 were 12 pounds lighter and faced a 54% lower risk of obesity than did people without the gene abnormality. 
  • These protective "loss-of-function mutations" were found in one out of every 3,000 people studied.
  • To further probe GPR75's role, researchers fed a high-fat diet to mice engineered to lack either one or two copies of the gene and mice with two functioning copies. 
  • The normal mice doubled their weight in 14 weeks. Mice with just one functioning copy of GPR75 gained 25% less body weight, while those that lacked both copies of the gene gained 44% less. 
  • Glucose tolerance and insulin sensitivity also improved in mice engineered to lack either one or two gene copies.
  • Regeneron will investigate several different alternatives for targeting the gene in obesity, including gene-silencing drugs, antibodies, and small molecules. 
  • Price Action: REGN shares closed at $574.6 on Thursday.
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