Across disciplines, therapeutic areas and even continents, Pfizer scientists have been working to advance understanding of – and potential treatments for – cachexia, a complex metabolic condition associated with certain chronic conditions, such as cancer and characterized by severe weight loss, decreased appetite, fatigue and muscle wasting. Its symptoms can often be misattributed and there are currently no FDA-approved treatments targeting its root cause.
But, over the past decade, the landscape of cachexia research has evolved and researchers have made significant progress uncovering the intricate, multifactor biological mechanisms driving this devastating condition. At the heart of this research is a protein known as growth differentiation factor-15 (GDF-15), a cytokine acting like a stress signal in the body, which can influence patterns of weight loss and muscle wasting in patients with chronic illness.
Recognizing the urgent need for treatment options and guided by patient insights, Pfizer scientists have discovered a way to decrease the level of GDF-15 circulating in the body in order to potentially help patients living with cancer cachexia.
The team was able to solve the crystal structure of an antibody bound to GDF-15, revealing where receptors might bind and how the antibody attaches to the protein. This breakthrough uncovered fundamental biology that laid the foundation for a treatment approach.
They combined multiple cutting-edge technologies, including advanced display-based techniques to develop potential antibodies, applying AI and machine learning to predict potential molecular interactions and creating custom libraries that could optimize multiple drug properties simultaneously.
The program’s success thus far has been the result of multifaceted collaboration – researchers, clinicians and scientists working seamlessly across different research units around the world. Their shared commitment enabled the development of innovative techniques and steady advancement of a promising investigational therapy, starting at its earliest conception in Pfizer labs. The team even drew on a newly developed, homegrown technology, which enabled scientists to engineer out unwanted elements from drug candidates to help predict and improve efficacy early in the drug discovery process.
As the team works to increase understanding of GDF-15’s involvement in cachexia, they hope to shed valuable light on the mechanisms by which it influences weight loss and muscle wasting, which will guide future research efforts and potentially help improve patients’ lives.
Watch the video below to see “Behind the Science” of this team’s work:
When Matthew’s daughter was diagnosed with cancer, he watched as cachexia complicated her treatment, an experience that has deeply influenced his passion for his work today. Learn more:
After meeting a patient living with cachexia, Danna too felt an even deeper connection to her work, reinforcing her desire to help deliver treatments to the many people who need them. Learn more:
When Laura’s uncle was struggling with advanced-stage cancer, there was no treatment available for cachexia. Laura reflects on what such a treatment might have meant for his survival. Learn more:
Learn more about Pfizer’s medical innovations and the people behind these advancements by visiting Pfizer.com.
