What does 2026 hold for DADA2?
As we head into the new year, we are hopeful that new scientific discoveries and increased support for newly diagnosed patients and their physicians will ultimately improve the lives of patients and help identify the undiagnosed. We invite you to be a part of this important mission with a one-time or monthly gift. Your generous contribution of any size is critical to continue all of the work you see below.
Are you READY to join us?
Research Highlights in 2025
There is a lot of global research happening around DADA2, and you can check out a full, constantly updated list here whenever is convenient to you. In this 5-minute video with our Chief Scientific Officer Lex Cowsert, we dig into one piece of important research around the impact of DADA2 on those who are carriers. Get ready for a bit of a genetics lesson here to help you understand DADA2 variants and other important factors. There may be more nuance than we think! Read the full research paper here.
What is PEG-ADA2?
PEG-ADA2 is in its very early stages of being explored as a potential treatment for DADA2 by replacing non-existent ADA2 in the bodies of patients. As DADA2 Foundation Chief Scientific Officer Lex Cowsert will explain, we are still years away from this being used with patients but we are actively pursuing the studies and steps that can help us determine just how effective it can be. Watch this 4-minute video for a primer on how PEG-ADA2 can work and what steps it will take to confirm its effectiveness.
Testing for DADA2 in Office
Up to now, testing for DADA2 has been an arduous process for most. DADA2 Foundation Chief Scientific Officer Lex Cowsert explains a point-of-care test that we are working to develop that could give suspected DADA2 patients a measure of their ADA2 levels right in their doctor’s office, in a matter of minutes. While it is not yet on the market, we are pursuing the development of such a device with a partner. Watch this 4-minute video to learn more.
READY to CURE DADA2
Content: It’s a privilege to wrap up 2025 with so many interesting and exciting paths to pursue in 2026. Each story this month points to where we’ll head in the new year and how you can come alongside to support the Foundation in our work. This year, we are looking for 50+ monthly donors to sign on and give a little each month. Every little bit adds up to support our mission of curing DADA2, convening the researchers, resourcing the patients, and supporting physicians as they navigate new diagnoses.
Join Our Newsletter
Join our monthly newsletter which highlights work being done around the globe to cure DADA2 and guide patients living with the disease. Visit the newsletter archive to learn more.
Q&A With Dr. Pui Lee: Biology Behind DADA2
When DADA2 was first discovered in 2014 very little was known about the role ADA2 played in the body. Since then, with the encouragement of the DADA2 Foundation, researchers have been attacking the issue from many research angles. The DADA2 Foundation reached out to Dr. Pui Lee of Harvard/Boston Children's Hospital to learn more about his research on the fundamental biology of ADA2 and why it is important for developing better treatments for DADA2.
Q: Dr. Lee, what are you hoping to understand through your current DADA2 research?
A: My team is trying to understand the chain of events that happens when the ADA2 enzyme is missing or not functioning properly. ADA2 normally helps regulate how certain immune cells behave — especially monocytes and macrophages. When ADA2 is low, these cells can shift into a more inflammatory state. We want to identify exactly how that shift occurs and why it leads to the symptoms families see in DADA2.
Q: Why is inflammation such an important part of this disease?
A: In DADA2, inflammation isn’t random — it comes from specific immune pathways becoming overactive. We are especially interested in how the loss of ADA2 leads to excess production of inflammatory cytokines, including TNF, and how this affects the lining of blood vessels. Understanding these pathways will help us explain why some people develop vasculitis or strokes, while others may experience immune deficiency or bone marrow problems.
Q: How could this research help people living with DADA2 right now?
A: Learning the underlying biology helps us refine treatment. For example, anti-TNF medications work for many families, but not all. By understanding the deeper mechanisms — such as dysregulated macrophage activation, type I interferon pathways, or abnormalities in blood-vessel repair — we can look toward more targeted therapies. This may also help us determine which treatments are likely to work best for specific patients.
Q: Will this research help improve diagnosis?
A: Yes, that’s one of our goals. We hope to identify biological markers — things we can measure in blood or immune cells — that clearly show when ADA2 function is reduced. These biomarkers could be especially helpful when genetic testing identifies variants of uncertain significance. A measurable signal in the immune system could help confirm the diagnosis more quickly.
Q: What about more serious complications, like strokes or bone marrow failure?
A: We want to understand why the same ADA2 deficiency can lead to such different outcomes. Part of our work focuses on how ADA2 supports healthy development of blood cells and the stability of blood vessels. If we can clarify why certain pathways fail — for example, why some patients have defective endothelial repair or abnormal macrophage activation — we may be able to predict risk earlier and intervene more effectively.
Q: What does this research mean for the future?
A: By mapping the immune and cellular pathways affected by ADA2 loss, we’re creating a roadmap for new treatments. This knowledge is essential for developing improved enzyme replacement, gene therapy approaches, and therapies that correct the specific inflammatory signals involved. Ultimately, the goal is to move beyond treating symptoms and toward therapies that address the root cause of DADA2.
Q: How might this research be useful to people outside the DADA2 community?
A: Although our work focuses on DADA2, the pathways we’re studying are part of the broader immune system, so what we learn may help many other conditions. ADA2 influences how monocytes and macrophages mature, how blood vessels repair themselves, and how inflammatory cytokines — like TNF and interferons — are regulated. These same pathways are involved in other types of vasculitis, autoimmune diseases, bone-marrow disorders, and even some infectious and vascular conditions.
By understanding how ADA2 deficiency disrupts these systems, we may uncover principles that apply far beyond a single rare disease. Insights from DADA2 can guide new approaches to controlling inflammation, protecting blood vessels, and improving immune recovery in other disorders. Rare diseases often shine a spotlight on pathways that matter for many people, and DADA2 is a powerful example of that.