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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