Phenotyping Personalizes Obesity Treatment

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ARTICLE SUMMARY:

The most impactful innovation in obesity right now is a diagnostic, not a GLP-1 drug. Excerpted from our recent interview with Phenomix Sciences founder Andres Acosta.

As of April 2024, Phenomix Sciences has launched three out of four phenotyping tests in its MyPhenome platform, which has been developed to help clinicians determine their patient’s particular obesity syndrome, so they can deliver targeted treatments across any class of obesity therapy, be it drug, diet, endoscopic device, or surgery. (These are simple, saliva-based tests that require a cheek swab; they’re as easy to administer as a consumer ancestry test, but they deliver all the biomarkers necessary to type a patient’s obesity.

Andres Acosta, MD, PhD, a gastroenterologist and director of the Precision Medicine Obesity Program and associate professor of medicine at the Mayo Clinic, says he co-founded Phenomix Sciences (along with Michael Camilleri, MD, also of the Mayo Clinic, where he is a full professor of medicine) to address what he calls the “rule of thirds” in obesity care. Acosta jokes that working in mouse models, he cured obesity three times. But when he dug into the human literature, “I noticed that for every single intervention, whatever diet is trending, drugs, bariatric surgery, and everything in between, a third of patients do great, a third just so-so, and a third don’t respond. The question we wanted to answer is, ‘Why?’”

To solve that problem, the Mayo Clinic researchers spent 12 years exhaustively studying patients from a genetic and physiological standpoint to understand what drives variability in obesity treatment response. The MyPhenome biomarker test was ultimately developed using AI to create a machine-learning polygenic risk score of gene variants from 22 genes and selected demographics. 

Acosta and Camilleri found four subtypes of obesity: Hungry Gut, which describes patients with abnormal satiety, who, because they experience accelerated gastric emptying, feel hungry again shortly after eating; Hungry Brain, which applies to patients who consume excess calories without feeling full; Emotional Hunger, that is, the situation where people eat for a reward or in response to emotional triggers; and Slow Burn, where a patient’s low rate of energy expenditure facilitates weight gain.

The first three tests have been launched as MyPhenome, which allows clinicians to test for all three phenotypes, also revealing if patients have more than one of the phenotypes, which, the company’s research suggests, calls for more aggressive management (according to an article published in Nature’s International Journal of Obesity in February 2024; Acosta is a co-author.) Acosta and other researchers continue to study the links between obesity phenotypes and the likelihood of response to specific therapies, with a goal of personalizing therapy to maximize weight loss. MyPhenome helps personalize bariatric device therapies as well as drugs; Acosta says researchers working with the company’s platform have published several studies to this effect.

MyPhenome tests helps debunk the “personal responsibility” myth (the simplistic view that to lose weight, people just need to “eat less, and move more”) that has resulted in such poor outcomes to date. Obesity phenotyping enables a doctor-patient conversation that empowers patients. Patients will now understand their genetic propensity to patterns leading to obesity, and why they should engage with specific interventions. Equally important, precision obesity is cost-effective. When clinicians can match patients with a therapy that operates on the physiological (or cognitive) mechanism underlying their syndrome, outcomes improve, and time and money spent on interventions unlikely to work for patients is spared. Going back to Acosta’s rule of thirds, today, two-thirds of the obesity healthcare that we are paying for is ineffective.

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