Helping Children with Asthma

A team of researchers motivated to help children with asthma is conducting a novel study with mesenchymal stem cells to help reduce airway inflammation and symptoms in affected patients. Drs. Ed Horwitz (sponsor investigator), Anne Fitzpatrick (scientific investigator), and Lokesh Guglani (clinical investigator) are leading this first of its kind study.

Asthma is the most common chronic disorder of childhood, but current treatment options leave a lot of room for improvement. In fact, Dr. Fitzpatrick says 1 out of 2 children are not doing as well as they could be with their asthma, even with appropriate treatment. “We also have children with severe forms of asthma who are unable to attend school due to breathlessness and persistent respiratory symptoms. These children have frequent exacerbations that result in recurrent hospitalizations. These children also have significantly impaired quality of life since they can’t function like typical children.”

While national treatment guidelines provide guidance for the management of asthma, the number of FDA-approved medications available for children with asthma is quite limited. Another challenge with most available asthma medications is that they must be inhaled using exactly the right technique for proper efficacy. “There are significant problems with airway deposition of drugs in patients with asthma, so we are constantly looking for new ways to treat airway inflammation. That’s why novel therapies such as mesenchymal stem cells have a lot of promise,” says Dr. Fitzpatrick.

The mesenchymal stem cells that Dr. Horwitz has studied his entire career are potently anti-inflammatory. The activity of mesenchymal stem cells is mediated by a variety of cell-to-cell contacts and soluble mediators which have direct effects on immune cells and tissue. The hope is that these stem cells can “heal” damaged airways in children with asthma.

In this first-of-its-kind phase 1 clinical trial, two preparations of mesenchymal stem cells will be infused up to 24 children with asthma through a dose-escalation design. The primary objective of the trial is to demonstrate safety of the stem cell products. Enrollment is expected to begin in Spring 2021.

Dr. Horwitz says, “Think about the possibility. If the study proves safe and then effective, you could see your doctor once every four months, get an infusion for 15 minutes, and have no problems with your asthma the rest of the year. You could play sports, or go outside on a cold day. This would be a major advancement in the treatment children with asthma.”

There are studies of mesenchymal stem cell infusions in mice with experimental forms of asthma, but this will be the first study of its kind in humans. In mice with experimental asthma, the mesenchymal stem cells locate to the airways within 24 hours of administration and attenuate the histopathologic manifestations of asthma. It’s unclear if the same effects will happen in humans, but this study will give researchers initial insight on how the mesenchymal stem cells behave after administration.

“In research, you have to dream of what does not exist, but could exist, and how do you make it exist.” says Dr. Horwitz. “You’re going to be wrong sometimes, but sometimes you’re going to be right and when you’re right, a lot of kids get better. There’s huge potential here to help children with asthma and advance the therapeutic options, so we have to try.”

Dr. Fitzpatrick has been conducting research for 16 years and joined the Emory Department of Pediatrics in 2004. She was inspired to get into research when she was training. “I fell in love with the questions that could be addressed. We’re trying to address gaps in clinical medicine. When you practice clinical medicine for a while, you realize there’s a number of holes that can’t be answered. The types of studies we do are ultimately designed to impact care, so we’re trying to improve the care we deliver to children with asthma and come up with better treatments.”

This is Dr. Horwitz’s 25th year doing research and he has been at Children’s + Emory for three years. He started doing research in college as an undergraduate student because he really enjoyed it and planned to go to medical school to become a doctor. “When I was in medical school, I realized I missed the intellectual challenge of research. I thought about it, and I decided I wanted to go into academic medicine with the idea that I would not only take care of patients, but could also do research to make a difference for patients.”

Dr. Guglani has been involved in clinical and translational research for 20 years. He joined Emory Department of Pediatrics in 2015 and has been instrumental in starting new programs related to chronic respiratory disorders such as Cystic Fibrosis early lung disease monitoring program and Primary Ciliary Dyskinesia. While treating patients with various respiratory disorders (majority of which tends to be asthma), his focus has always been on the underlying mechanisms of disease processes and how they could be understood and treated better. “There are so many respiratory disorders in children for whom we do not have effective treatments yet, and we can only hope to control some of the manifestations of the disease process, which is not enough. We need to do a better job at finding effective therapies for common respiratory problems that affect the lives of our patients and their families.” 

The Marcus Foundation is funding $3.45 million to advance this important project including but not limited to experimental therapeutics, clinical tests, preparing cells, and more. This research team is extremely grateful to the Marcus Foundation for having confidence in them to get this trial going. “We are so grateful they are supporting a novel study,” says Dr. Horwitz. “This is the first study of its kind and it’s incredibly innovative. It might have a huge impact on the treatment of children. Without the Foundation’s funding, we could not do this.”