A groundbreaking triple-drug combination called Trikafta has provided a new lease of life for 90% of individuals with cystic fibrosis, an inherited disorder that primarily affects the lungs and other organs. The triumphant trio of researchers behind the development of Trikafta, Sabine Hadida, Paul Negulescu, and Fredrick Van Goor at Vertex Pharmaceuticals in San Diego, California, have been honored with one of this year’s prestigious US$3-million Breakthrough prizes, recognized as the most lucrative awards in the realm of science.
Trikafta’s development involved combining various drugs that assist a malfunctioning protein in functioning properly. This achievement has been hailed as one of the most remarkable and outstanding feats in biomedical research over the past three decades. Francis Collins, a geneticist, and physician at the US National Human Genome Research Institute, who co-discovered the cystic fibrosis gene in 1989, lauded the development of Trikafta.
According to Scientific American, Cystic fibrosis is a genetic condition caused by mutations in the gene responsible for producing the cystic fibrosis transmembrane conductance regulator protein (CFTR). This protein usually spans cell membranes in multiple organs and plays a role in the production of mucus, sweat, and other bodily fluids. In individuals with cystic fibrosis, these CFTR proteins are misfolded and fail to function correctly. This results in the buildup of unusually thick secretions, including mucus in the lungs, which leads to severe health complications.
Traditional approaches to treating cystic fibrosis focused on modifying the malfunctioning CFTR gene itself, but these efforts yielded limited success. The team led by Hadida, Negulescu, and Van Goor took a different approach. Instead of modifying the gene, they sought to find a combination of drugs that could coax the misfolded CFTR proteins into functioning properly. Trikafta consists of three drugs that work in concert: two facilitate the delivery of more CFTR to the cell surface, while the third enhances the protein’s functionality once it reaches the surface.
The drug discovery process was an arduous undertaking, involving the testing of over one million compounds on isolated human lung cells to identify potential drugs for clinical trials. Sabine Hadida expressed her excitement, honour, and surprise at receiving the Breakthrough prize, emphasizing that credit should be shared with the company, individuals with cystic fibrosis, and their families.
Trikafta and similar drugs approved by the US Food and Drug Administration in 2019 have the potential to significantly increase the life expectancy of individuals with cystic fibrosis, potentially extending it from around 30 years to over 80 years. Many individuals who were once severely affected by cystic fibrosis, to the point where it jeopardized their survival, have experienced a remarkable turnaround after starting treatment with Trikafta. They have been able to return to work and contemplate their future, including retirement.
This breakthrough has provided a newfound sense of hope for the cystic fibrosis community and represents a triumph in the field of medical research. It has transformed what was once considered a life-limiting condition into a manageable one with the potential for a significantly extended lifespan.
The Breakthrough Prize also recognized other outstanding achievements in the field of life sciences. Another prize was awarded for the independent discovery of two genes associated with the risk of developing Parkinson’s disease: GBA1, identified by geneticist Ellen Sidransky at the NHGRI (National Human Genome Research Institute), and LRRK2, discovered by neurogenetics Andrew Singleton at the US National Institute on Aging and neuroscientist Thomas Gasser at the University of Tübingen, Germany.
Ellen Sidransky’s work originally focused on the rare hereditary disorder Gaucher disease, which involves the GBA1 gene. However, she noticed that many individuals with Gaucher disease also had relatives with Parkinson’s disease, leading her to make the connection. This discovery has the potential to shed light on the broader population’s susceptibility to Parkinson’s disease and is a testament to the importance of research into rare diseases.
Additionally, immunologists Carl June at the University of Pennsylvania and Michel Sadelain at the Memorial Sloan Kettering Cancer Center were awarded a Breakthrough prize for their development of CAR-T-cell immunotherapy for leukaemia. This revolutionary treatment stimulates a patient’s immune T cells to target and eliminate cancer cells, leading to prolonged remission in some cases.
The Breakthrough prizes, founded in 2012, are sponsored by prominent figures in the tech industry, including Russian-Israeli billionaire Yuri Milner and Mark Zuckerberg, the CEO of Meta (formerly Facebook). These prizes celebrate and reward remarkable achievements in the fields of life sciences, physics, and mathematics, providing both recognition and substantial financial support to the recipients. These awards highlight the critical role that scientific research plays in advancing our understanding of the world and improving human health and well-being.
