The Battle Against Obesity Heats Up

May 2022

Patients suffering from obesity have had no safe options to turn to when diet and exercise fail. Until now

When humans first roamed the earth, our bodies’ natural heat production kept us warm and helped us survive while we hunted and gathered in freezing temperatures. Our world has developed so rapidly since then that our biology is now working against us. The luxuries of modern life have allowed us to live in warmer conditions, slowing down our natural heat processes and creating insulin resistance, which leads to weight gain. This renders the typical weight-loss admonitions (diet and exercise) inadequate for many patients. The result? Nearly half of the adults in the US suffer from obesity and metabolic syndrome, putting them at higher risk for disease and cancer, and costing the economy up to $1 trillion every year.

Besides diet and exercise, heat production by our bodies is the third mechanism that can be instrumental in losing weight. Microscopic cellular organelles called mitochondria generate heat as they burn nutrients that we consume with food. Currently, there are no FDA-approved drugs that can increase caloric burn rate through activation of mitochondrial heat production, and the alternatives on the market cause side effects like muscle atrophy or nausea. Patients suffering from metabolic disorders have no safe options to turn to when exercise and diet fail.

Luckily, we are very close to having a solution thanks to the work of Yuriy Kirichok, Ph.D., and Jonah Sinick, Ph.D. Their company, Equator Therapeutics, aims to unlock natural heat production mechanisms in mitochondria to reverse metabolic disorders. They have discovered the mitochondrial protein that activates heat production in cells, and their high throughput drug discovery platform is capable of identifying drug candidates to activate this protein safely, without side effects. While they are still in the early stages of development, Equator Therapeutics is going to be a game-changer for patients.

The company’s ethos is largely shaped by effective altruism, a philosophy centered around making systematic decisions to optimize collective wellbeing. It’s the very reason why Sinick, the CEO, decided to co-found Equator Therapeutics. Ideas from Effective Altruism influence every aspect of the company, he says, “from hiring to the selection of chemical compounds for experiments. We are oriented toward doing what gets the job done without being constrained by what is conventional.”

Sinick’s most fulfilling moment building the company came during his first pilot test run of their “screen” — one that would identify compounds that activate their target protein. What the screen returned was a summary of virtually everything known up until now about mitochondrial heat production activation. “It was then that I realized that we would soon far outstrip the current state of human knowledge,” Sinick recalls, “and that our program would be successful to the fullest extent that I could hope for.”