The findings offer promising support for progressing ADPO-002NP treatment to first-in-human Phase I clinical trials.
Adipo Therapeutics LLC, a late-stage preclinical biopharmaceutical company focused on developing treatments for obesity and related metabolic disorders, recently presented findings from two studies at The Obesity Society’s annual meeting in San Antonio.
The studies were designed to evaluate the impact of Adipo’s active ingredient ADPO-002 on key browning markers for mitochondrial biogenesis, mitochondrial activation, and adipocyte browning in human fat cells and fat tissues.
The increases in PGC1⍺, PRDM16 and Uncoupling Protein 1 (UCP1) in these studies support ADPO-002’s mechanism of action for mitochondrial biogenesis, activation and browning of human white adipose tissue, and the potential for the translation of Adipo’s treatment to humans.
Why brown adipose tissue matters
Obesity is a significant public health crisis. According to the National Institutes of Health, by 2030 nearly half of U.S. adults will be obese. People who are overweight or are affected by obesity are at increased risk for many serious diseases and health conditions including Type 2 diabetes, fatty liver and gallbladder diseases, high blood pressure, dyslipidemia, cardiovascular diseases, sleep apnea, breathing disorders, osteoarthritis, mental illness, and some cancers.
Excess energy-storing white adipose tissue is associated with obesity, Type 2 diabetes mellitus, and cardiovascular disease whereas energy-burning brown adipose tissue plays a beneficial role in overall metabolic health. Brown adipose tissue has a high number of mitochondria, increases energy expenditure, and is associated with improved insulin sensitivity and decreased risks for Type 2 diabetes and cardiovascular disease, according to a 2021 published article in Nature Medicine titled “Brown adipose tissue is associated with cardiometabolic health.”
Adipo’s lead product ADPO-002NP has a unique mechanism of action that has the potential to be a stand-alone treatment or a complementary product to existing weight loss and diabetes drugs given its ability to increase energy expenditure and improve insulin resistance by browning white adipose tissue.
“While weight loss can be achieved through decreasing calorie intake and/or increasing energy expenditure, the newer therapies on the market are focused primarily on appetite suppression to reduce a person’s daily caloric intake,” said Adipo CEO Karen Wurster. “There is a need for new weight-loss products that work by increasing energy expenditure without requiring calorie restriction. Adipo’s treatment has the potential to increase energy expenditure by creating healthier, energy-burning, metabolically beneficial subcutaneous fat.”
Results of the studies
The first study examined the effect of ADPO-002 and ADPO-002NP on differentiated human white adipocytes obtained from the Pennington Biomedical Research Center in Baton Rouge, Louisiana, in collaboration with Shihuan Kuang, who was previously a professor and researcher at Purdue. The study demonstrated a significant increase in PGC1⍺ and inhibition of Notch target gene Hes1.
The second study examined the effect of ADPO-002 on subcutaneous and omental adipose tissue explants obtained from bariatric surgery patients who provided consent. The human adipose tissue explants study was conducted by Adipo Therapeutics in collaboration with Robert Considine, professor of medicine in the Division of Endocrinology at Indiana University School of Medicine in Indianapolis and Ascension St. Vincent Hospital Carmel. It demonstrated a significant increase in critical browning marker genes PGC1⍺ and PRDM16 following seven days of treatment. It also showed an upregulation of UCP1, a key regulator of thermogenesis in both subcutaneous and omental tissue following treatment.
The changes observed in these studies support Adipo’s mechanism of action for mitochondrial biogenesis and browning of human white adipose tissue.
“Inhibition of Notch signaling has been shown to promote adipocyte browning in our previous animal studies. Our findings from these studies with human adipocytes and adipose tissue explants provide important encouraging evidence for the translational potential of this novel mechanism of action,” said Adipo founder Meng Deng, associate professor in Purdue University’s Department of Agricultural and Biological Engineering, Weldon School of Biomedical Engineering and School of Materials Engineering.
Deng disclosed his research to the Purdue Innovates Office of Technology Commercialization, which applied for patents to protect the intellectual property. It licensed the technology to Adipo for development and commercialization.
Adipo is currently raising $8 million in additional funding to move this breakthrough product to first-in-human Phase I clinical trials, which are designed to demonstrate safety and clinical proof of concept in people. The capital will enable the team to continue its efficient execution to advance ADPO-002NP including good manufacturing practices, preclinical toxicology studies and regulatory approval to begin the Phase I clinical development.
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2 Comments
As a now an eighty year old lay American male victim, investigator, experimenter and discoverer with a forty-three year history of externally imposed chronic illness briefly browsing all of the SciTechDaily dot com medical articles this morning of 11/12/24, I find they all have causal similarities to what I’ve been writing about for nineteen years and counting, beginning with the US FDA (with replies) about my early lay findings of connections between food (minimally) allergy reactions, added MSG, chronic disease and obesity in October of 2005 (obviously, now, in-vain).
Simply put, most of global mainstream medicine is still ignorant and incompetent of my kind of food allergies, officially approved food poisoning and excessive related/resultant medical errors. And, no medical study that fails to factor-in those is even worth the time it takes to read it. Government and science have already failed to improve upon nature, replacing evolution with devolution. What most of us really only need to be healthy, starting with pre-conception parents, is to know what allergens (if any) to avoid, alternate and or rotate, as pure, safe and natural commercially prepared food products as are possible and properly educated healthcare professionals we can afford and trust. There will be exceptions to the rule, of course, but they should be the minority, not the majority. More details on my non-monetary video channel “About” page: https://odysee.com/@charlesgshaver:d?view=about
I disliked the article for being a commercial. It used phrases like “active ingredient” and “mechanism of action” to hide what it is and what it does. A university like Perdue shouldn’t be hiding knowledge.
The drug alpo002 thing is dibenzazepine (via Bioworld), the basis of drugs like oxcarbazepine or carbamazepine used to treat epilepsy, or depramine used as an antidepressant. The NP seems to denote “NanoParticles”, of PLGA (via Adipotheraputics), polylactic glycolic acid, a polymer. They can inject the polymer once a week, which degrades in the body, giving off a constant dose of dibenzazepine. This apparently signals the nearby white fat to turn brown, using more calories, or that’s their hope.
They only tested the drug on some fat cells in test tubes. Since it’s not even in a Phase 1 trial yet, this is all completely hypothetical and there is no treatment here, yet. Maybe it works, maybe it doesn’t, maybe it does nothing, maybe patients grow wings and fly away. The article is beyond optimistic. Anyone overweight wanting to be injected with antidepressant plastic shouldn’t hold their breath for the decade it’ll take to test this.