The Albany Gazette - Scientists behind breakthrough cystic fibrosis treatment awarded top US prize

And on Thursday the three scientists who developed the clinical advance were awarded America's most prestigious scientific award, taking home the Lasker prize.

The top honor is frequently cited as a pre-cursor for a potential Nobel, and this year it recognized the pulmonologist Michael Welsh along with researchers Jesus Gonzalez and Paul Negulescu from the US laboratory Vertex.

Their research has shed light on the causes of the disease and given rise to a new class of innovative drugs, including the flagship treatment Kaftrio -- known as Trikafta in the United States -- which are capable of stabilizing the otherwise debilitating condition.

"It's unbelievable. It's better than I ever hoped," Welsh told AFP. "You see these kids and they look healthy and they're not coughing. They're running around and playing."

"I almost can't believe it. Then they go, and they're getting married and they're having kids, and they're getting on with their lives."

That reality stands in sharp contrast to Welsh's memories from the early days of his career, when a cystic fibrosis diagnosis was a likely death sentence in childhood or adolescence.

The new award-winning treatment has been hailed as "revolutionary" by patient advocacy organizations.

It works by addressing the underlying causes of the inherited disease -- which wreaks havoc on the lungs and digestive system -- rather than its symptoms.

- 'Not totally broken' -

Some 100,000 people worldwide are estimated to suffer from cystic fibrosis, in which sticky mucus builds up in the lungs, digestive tract and other parts of the body.

After the 1989 discovery of the CFTR gene -- whose mutation was identified as the cause of the disease -- Welsh began dissecting the problem with fellow researchers.

"We thought, if we understand how CFTR works, we have a chance of fixing it," he said.

Gaining a better understanding of how the protein that the gene codes for led the pulmonologist down a path seeking how genetic mutations impaired its function.

Welsh identified two major anomalies caused by the most common mutation: a trapping of sorts of the protein within the cell, and its reduced performance.

The medical breakthrough resulted from experiments, notably some that showed how lowering temperature could help release the trapped protein.

"That meant it was not totally broken," Welsh remembered enthusiastically.

Armed with these discoveries, the American Cystic Fibrosis Foundation then approached researchers Gonzalez and Negulescu, who began studying the possibility of chemically reversing the identified malfunctions.

- 'Panning for gold' -

The notion of gene therapy -- which would aim to directly reverse the gene mutations -- had seemed on paper to be the simplest route.

But when it didn't work as hoped, patient organizations began to explore other options.

Gonzalez developed an innovative research technique using dyes that allowed for testing thousands of chemical compounds in record times.

"Without the screening, we would never have found these molecules," he said.

It was process akin to "panning for gold," recalled Negulescu.

But ultimately their dogged work paid off; they identified a handful of molecules that led to the birth of a new class of treatments.

Those molecules proved capable of restoring mobility to the stuck protein, and improving its function.

Kaftrio/Trikafta -- approved stateside in 2019 and classified by the World Health Organization as an essential treatment in 2025 -- is among them.

But their significant cost poses an obstacle for some patients, especially as the treatment is lifelong, and the therapy is ineffective in a small minority of patients including those with different mutations.

"The work is not done," said Negulescu.

(S.Perez--TAG)