A promising new approach to combating eczema could help millions of patients who are left unsatisfied by current treatments. The key may lie in transcription factors—a solution that was previously considered impossible.
On Nov. 19, members of the McGill Department of Chemistry gathered in the Otto Maass Chemistry Building where Carla Spina, CEO and co-founder of Noa Therapeutics, presented her research and innovative therapeutic for the treatment of atopic dermatitis (AD), a form of eczema.
Eczema is a complex disease that affects one in 10 children worldwide. AD is the most common form of eczema. It falls under the category of inflammatory barrier diseases, which can cause disruption of the body’s barriers—such as the permeability barrier of the skin—and leave the immune system compromised.
Spina described three major drivers of inflammatory barrier diseases: Barrier dysfunction (breaches in the barrier itself), immune dysregulation, and microbial imbalance. She stated that current therapeutics focus primarily on the inflammatory pathway and do not directly address the above drivers of the disease or the underlying cause. In fact, 65 percent of patients with AD are non-responsive to current therapies.
“We see that the drugs on the market are not addressing all of the underlying factors of these kinds of inflammatory diseases. We are looking [at] a more holistic approach to addressing underlying drivers, not only from an inflammation perspective, but from a barrier perspective, and addressing the potential for infection,” Spina explained.
Spina detailed the use of transcription factors as therapeutic targets, specifically the aryl hydrocarbon receptor (AHR). Transcription factors are proteins that regulate genetic activity and influence important biochemical pathways. In the past, many scientists believed they were unsuitable as therapeutic targets, due to their inability to bind small molecules or drugs.
“Traditionally, transcription factors were thought to be undruggable. This is in part because a large number of transcription factors do not have discrete binding pockets or they are not accessible for small molecule therapeutics,” Spina said.
However, some transcription factors, including AHR, do have a binding pocket. According to Spina, AHR is even considered a “promiscuous receptor” due to its ability to bind a variety of ligands originating from both inside and outside the body. She explained how, when you hurt yourself, certain compounds can bind to AHR and promote healing pathways.
With her company, Noa Therapeutics, Spina developed NOA-104, a leading drug compound that targets AHR. Within the first six months of starting the company, the novel therapeutic demonstrated the ability to resolve barrier dysfunction and reduce oxidative stress in human skin cells, potentially decreasing inflammation associated with atopic dermatitis.
Spina, who studied at the University of Calgary before coming to McGill in 2003, has many loved ones who live with atopic dermatitis and said she was passionate about finding better methods of treatment for those with inflammatory barrier diseases.
“When we think about what we’re here for, we’re not here for the molecules, we’re not here for the science, although that part is really fun. We really focus on people, on patients,” Spina said.
Looking ahead, Spina and Noa Therapeutics aim for further translation of their drug into disease models, such as through validation in animal studies. However, as the complexity of atopic dermatitis presents numerous challenges, their team requires extensive testing to have a better understanding of the impact of their therapy.
“You always want to have a clear understanding of what the implications are in a real disease state [….] Because again, atopic dermatitis is very heterogeneous,” Spina said.
Finally, Spina opened the door to addressing a broader range of inflammatory diseases, including multiple sclerosis and inflammatory bowel disease—conditions with pathological similarities to atopic dermatitis. She emphasized the need to review current models of therapy and continue driving innovation to ensure impactful advancements that improve the quality of disease treatment.
