Research

Global Biopharma GiantGSK and BU AnnounceCollaboration to Pioneer NewLung Disease Treatments

Linkup aims to drive research into pulmonary fibrosis, a disease with no existing cure

CReM researchers and staff gather with GSK representatives and University and state officials to
celebrate the new partnership.

It’s a disease that can literally take your breath away—and there’s no cure. As pulmonary fibrosis progresses, it causes scarring in the lungs, making it harder and harder to absorb oxygen into the bloodstream. For many of those with the most common form of the disease, idiopathic
pulmonary fibrosis, life expectancy is less than five years.

A new collaboration between the global biopharma giant GlaxoSmithKline (GSK) and researchers from the Center for Regenerative Medicine (CReM) of Boston University and Boston Medical Center (BMC) could bring hope to the millions around the world with the relentless condition, as well as other lung diseases.

Together, they aim to use CReM-developed lung cells to better understand pulmonary fibrosis and to identify new drug targets to halt or slow its progression. United Kingdom–based GSK will provide funding and indirect support.

“This exciting collaboration with GSK will help BU, BMC, and CReM to make meaningful progress in the treatment of chronic lung diseases like pulmonary fibrosis,” says Darrell Kotton, MD, CReM’s founding director.
“Together with GSK, we are poised to advance emerging research discoveries into real-world therapies for patients.”

Pulmonary fibrosis, a type of interstitial lung disease, has a multitude of potential causes, including cigarette smoke, autoimmunity, and disrupted genes. As it gradually scars and stiffens the tiny air sacs in the lung known as alveoli, patients may feel shortness of breath and lose weight.

Existing medications can slow the disease’s progression, oxygen tanks can help alleviate symptoms, and a lung transplant might be an option for some patients, but clinicians soon run out of weapons to use against it.

For the past 20 years, Kotton and his team have been using stem cell technology to hunt for ways to study the onset and progression of lung disease. Their work has focused on using patients’ blood to create lung cells in the lab, so they can conduct research outside. of the body, or ex vivo. It involves a lot of cell reprogramming: turning blood cells into induced pluripotent stem cells (iPSCs), which returns them to an embryonic-like state, then nudging them to develop into lung cells. These cells become, e¢ectively, a model of the lung, allowing researchers to watch them “turn diseased in front of them,” says Kotton, the David C. Seldin Professor of Medicine.

“I give the analogy of a black box flight recorder, because you can replay all the events that led to the malfunction over and over,” he says. “You can understand the disease and then you can intervene at the set points where you want to stop the progression—and that’s where the drug development action is.”

Working with GSK, CReM researchers will significantly expand their bank of patient specimens, then apply those to modeling disease and developing new drugs.

“We have two applications for these cells,” says Kotton, who is also a pulmonologist and critical care specialist at BMC, BU’s primary teaching hospital. “One is to regenerate lung tissue in vivo through transplantation—we’re very excited and making rapid progress on that, but it’s a long way off. For drug development and discovery, I think it’s ready to go. How soon will new drugs be ready to apply in the clinic? I like to say, sooner than we think.”

The linkup’s initial period is three years, and Kotton and his colleagues hope BU and GSK will continue to work together after that.

“Through this collaboration, we are poised to make significant advances in understanding the molecular mechanisms behind pulmonary fibrosis, which could ultimately transform how we treat these devastating diseases,” says Kostas Alysandratos, MD, PhD, an assistant professor of medicine and codirector of the Interstitial Lung Disease Clinic at BMC. Along with stem cell biologist Andrea Alber, a CReM postdoctoral fellow, Alysandratos was one of the key players in developing the lung stem cells that will provide the foundation of the forthcoming work.

“At BMC, we are committed to conducting high-quality interdisciplinary research that is grounded in equity: 70 percent of our patient population identify as being people of color, and data suggest that Black patients with pulmonary fibrosis have worse health outcomes at younger ages compared to Hispanic or white patients,” says Megan Bair-Merritt, BMC’s chief scientific officer and a professor of pediatrics at BU’s medical school. “The collaboration with GSK will inform the development of new treatments for lung diseases that help address these disparities and pave the way for a healthier future for everyone.”

GSK is among the biggest pharmaceutical companies in the world. According to Kaivan Khavandi, MD, MRes, PhD, MBA MRCP, its senior vice president and global head of respiratory/immunology R&D, advancing new therapies requires “a deep understanding of the genetic and cellular basis of disease.”

“By working together to establish this scientific discovery collaboration,” he
says, “we will combine state-of-the-art translational models at the CReM, with extensive multiomic capabilities at GSK, to advance our understanding of the causal biology of fibrotic lung disease and accelerate the discovery of more effective treatments—which are so desperately needed in this area of respiratory medicine.”

Kotton first became interested in pulmonary fibrosis when he was training as a pulmonologist and became frustrated by the lack of treatment options. The new connection with GSK marks a major milestone in his journey toward providing a solution.

“We can really harness the power of the cells in a much more expansive way,” says Kotton of the collaboration’s potential. “What GSK does best is taking small molecules to a scale and safety level where they can be changed into drugs that can be administered to patients—and much more quickly than we could ever develop those kinds of approaches.”

One other recent CReM breakthrough used stem cell technology to develop cells for potential transplantation into injured lungs to treat damage and disease. And Kotton says it was BU and CReM’s reputation that sparked this new relationship.

“At BU and BMC, we’re known for iPSC-related lung research and, if a company is interested in applying those models to drug discovery in lung disease, it makes a lot of sense that they find us,” he says. “We like to say all research is translational. I think this is evidence that pursuing basic discovery—developmental biology, secrets of cell fate—inevitably translates.” ●