Three scientists have won a $250,000 award for their contributions to developing a life-saving therapy for the genetic disease cystic fibrosis (CF).
It’s one of this year’s Lasker Awards — biomedical-research prizes established in 1945 that are often called the “American Nobels.”
And even in the 2010s, before Trikafta’s approval in 2019, about half of CF patients died before age 40.
When functional, the gene enables cells to make tubes inside their membranes that charged particles called ions can flow through.
“Welsh, González, and Negulescu’s achievements are affording people with CF the chance to thrive now and to plan vibrant futures,” the statement says.
The development of a life-saving treatment for the genetic illness cystic fibrosis (CF) has earned three scientists a $250,000 prize.
Jesús (Tito) González of Integro Theranostics, Paul Negulescu of Vertex Therapeutics, and Dr. Michael Welsh of the University of Iowa were the recipients of the Lasker-DeBakey Clinical Medical Research Award. It is one of the Lasker Awards, which are biomedical research prizes that were first given out in 1945 and are frequently referred to as the “American Nobels.”. “..”.
González, who was previously Vertex Therapeutics’ senior director of biology, said, “It’s super gratifying.”. He told Live Science, “[In medical research], it’s very rare to actually have something that goes all the way to patients and is made widely available, and to have such a dramatic effect.”.
Patients who begin treatment in childhood or adolescence are expected to live near-average lifespans, and the treatment, known as Trikafta, extends the lifespans of people with CF by decades. In contrast, the majority of early childhood deaths occurred when the disease was initially identified in the 1930s. Even in the 2010s, roughly half of CF patients passed away before turning 40, prior to Trikafta’s approval in 2019.
In an essay about the award that was published in The New England Journal of Medicine, Dr. Eric Sorscher of Emory University stated that “the estimated median age of survival for persons with cystic fibrosis who were born between 2020 and 2024 and have access to treatment is 65 years.”. According to current estimates, health and longevity could improve even more as modulators are used at younger ages. “.”.
When you consider all of the people you’ve worked with, as well as all of the time and effort, the Lasker Award “also brings back a lot of great memories and it really warms your heart,” González continued. “I simply hope that people realize how challenging it is to get this far. “..”.
Related: A scientist receives a $250,000 Lasker prize for discovering the body’s “fire alarm” against invasive bacteria.
Mutations in the CFTR gene cause CF, an inherited disorder. When the gene is working, cells can create tubes through their membranes that allow ions—charged particles—to pass through. As a result, water can pass through tissues as it should and organs like the pancreas, intestines, and lungs can function as intended.
However, the CFTR gene is faulty in CF, which results in the linings of these organs becoming clogged with thick, sticky mucus. The mucus clogs airways, increasing the risk of harmful infections and lung scarring. It can also interfere with insulin signaling, digestion, and nutrient absorption.
The foundation for Trikafta, a medication that targets the molecular cause of the majority of CF types, was laid by Welsh’s laboratory research in the 1980s and 1990s. The “physiological consequences” of the most prevalent genetic error observed in CF patients were uncovered by Welsh and colleagues using cells from the disease’s airways, González explained.
Their research showed that the delta-f508 mutation in the CFTR gene prevents charged particles from more readily passing through the tubes in the cell membrane. Because of the mutation, the ions become stuck because the tubes never truly reach the cell’s surface. Welsh demonstrated how to make the tube reach the cell surface and improve ion transport in a number of experiments that involved cooling the cells as they developed in lab dishes.
González, meanwhile, co-invented a system that could precisely track the movement of ions across cell membranes in real time while working as a postdoctoral scholar in the lab of Nobel laureate Roger Tsien. According to him, the system’s original motivation was to investigate how the brain functions because ions passing through membranes allow brain cells to fire. However, the system was also ideal for testing possible novel CF medications that address the ion-transport problems.
González claimed, “This allowed us to screen tens of thousands of compounds a day.”. “At the time, electrophysiology—the accepted technique for thoroughly examining ion channels—was extremely slow, requiring only a few hours per day. “,”.
In order to find CF medications, the researchers improved the procedure at Aurora Biosciences, a biotech company that Vertex Pharmaceuticals later purchased.
Negulescu oversaw the initiative to screen molecules for their effects on ion transport while he was also at Aurora and then Vertex. His group searched for “correctors” to help move the tubes into the proper location in the cell membrane and “potentiators” to increase the flow of ions. Several CF medication iterations were approved as a result of this effort in 2012, 2015, and 2018, and Trikafta was finally approved in 2019.
González recalled, “It was really exciting because it became very real when they started getting data back from the earliest human trials of their first-generation drug.”. It’s like, “Wow, this isn’t just theory; patients are actually benefiting from it.”. “.”.
Most CF patients can be effectively treated with Trikafta, a combination of three medications. According to a Lasker Awards statement, its use has improved patients’ quality of life and decreased the number of lung transplants and hospitalizations for infection among those with the disease.
The statement claims that “people with CF are being given the opportunity to flourish now and to plan vibrant futures thanks to the accomplishments of Welsh, González, and Negulescu.”.
This year, two more Lasker Awards were given out: one for exceptional accomplishments in medical science and another for basic research.
The former award was given to Steven McKnight of the University of Texas Southwestern Medical Center and Dirk Görlich of the Max Planck Institute for Multidisciplinary Sciences in Germany. Low-complexity domains, which are intricate portions of protein sequences, have been shown to play important roles in how cells arrange their internal organs. These two researchers also investigated how this arrangement malfunctions in disease.
