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Macrocyclic molecules targeting specific protein-protein interaction in the adipocyte to restore function
AdipoPharma targets type 2 diabetes, a metabolic disorder characterized by a high level of glucose in blood lasting over a long period known as hyperglycemia. This multifactorial disease combines both the inability of the pancreas β-cells to compensate insulin needs in the organism and insulin resistance in tissues. Hyperglycemia leads to devastating complications such as cardiovascular disease, liver disease, blindness and kidney disease.
About 537 million people worldwide are affected by diabetes according to IDF. The total number is predicted to rise to 643 million by 2030 and to 783 million by 2045. Approximately 6.7 million adults are estimated to have died as a result of diabetes, or its complications in 2021. Our lead product PATAS, this first-in-class insulin sensitizing drug to treat type 2 diabetes and its associated comorbidities at the root.
The Adipocyte
The Adipocyte
The (white) adipocyte is a fascinating cell in myriad ways. It has been scientifically neglected for decades and was usually considered a mere storage tissue for excess caloric intake.
The adipocyte biology, however, is one of a kind with its transilient ciliated status during adipogenesis (Marion et al., PNAS 2009), which ultimately define the insulin sensitivity of the mature adipose tissue (Marion et al., Cell Metabolism 2012); scientific discoveries made by the study of human rare genetic disorders.
Nowadays, the adipocyte and its resident matrix — the adipose tissue — is recognized as essential for overall metabolic fitness as characterized by its high metabolic and endocrine activities.
Although the adipose tissue has garnered a high level of scientific attention due to the spiraling obesity pandemic, increasing insulin resistance in susceptible populations, and rising prevalence of type 2 diabetes, there is more than meets the eye when it comes to the adipocyte, best evidenced by the following observations:
- The adipose tissue absorbs only 10 % to 15 % of the overall circulating glucose, so has traditionally been regarded a minor player in driving type 2 diabetes (See figure).
- Obesity has been considered the main driver of insulin resistance in humans, but on the opposite side of the spectrum lipodystrophic patients and animal models, a condition where individuals lack adipose tissue, reproduce the exact clinical traits of insulin resistance, type 2 diabetes, and related comorbidities as those observed ine obese patients.
Hence, the adipocyte’s glucose absorption governs whole-body metabolic fitness, thus preventing insulin resistance, type 2 diabetes, and the associated deadly complications. Therefore, metabolic health is not dependent on the quantity of glucose absorbed but rather on the quality of the downstream products synthesized from the 10 % glucose.
AdipoPharma is harnessing the deep knowledge of adipocyte biology (Geberhiwot et al., Diabetes 2021) to design and develop a new class of therapeutic agents, for targeting the adipocyte (Schreyer et al., Diabetes 2022), thereby treating insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disorders, fibrosis, and other metabolic disorders.
AdipoPharma is harnessing the deep knowledge of adipocyte biology (Geberhiwot et al., Diabetes 2021) to design and develop a new class of therapeutic agents, for targeting the adipocyte (Schreyer et al., Diabetes 2022), thereby treating insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disorders, fibrosis and other metabolic disorders.
