Momentum, Discovery, and Hope: Summer Updates from the DADA2 Foundation
Global Progress and New Possibilities in DADA2
Dear DADA2 Community:
As we enter the heart of summer, I’m excited to share some important updates from the DADA2 Foundation. This season’s newsletter highlights the incredible momentum we’re seeing across the global DADA2 community — from growing international partnerships and new treatment possibilities, to cutting-edge research expanding our understanding of the ADA2 enzyme.
You’ll read about our continued efforts to raise awareness in under-resourced regions, our participation in global conferences that fuel collaboration, and an exciting new partnership with TNF Pharmaceuticals to explore a compassionate use study of Isomyosamine for patients who have few other options.
We also spotlight new science that’s helping us better understand how ADA2 works — not just in the blood, but within the cell itself — offering hope for more personalized and effective treatments in the future.
Whether you’re a patient, caregiver, clinician, or researcher, your commitment fuels our progress. Thank you for being part of this remarkable community. We hope you find this newsletter informative, inspiring, and energizing.
Chip Chambers, M.D.
Founder & President, DADA2 Foundation
Global Momentum for DADA2 Awareness
For the second year in a row, the DADA2 Foundation has been a sponsor of the Annual PAFLAR conference in Africa. In late April, Seza Ozen from Hacettepe University in Ankara, Turkey, introduced DADA2 to over 75 healthcare professionals from Nigeria, Africa, and beyond. The Foundation also gave out the DADA2 Physician’s brochure to the participants and encouraged anyone interested to reach out to the Foundation to get the brochure translated. We’ve had a few physicians interested and are currently working on a Swahili translation.
Many African physicians face limited resources, so the Foundation is eager to find ways to help with diagnosing and treating DADA2 patients diagnosed on the continent.
Back in the United States, the Foundation’s Chief Scientific Officer, Lex Cowsert and Executive Director, Mary Makley, attended the Rare As One conference in late May. Once a year, the Chan Zuckerberg Initiative brings together all the patient advocacy organizations who have received Rare As One grants.
The DADA2 Foundation was part of the first cohort in 2019. Though we no longer receive money from the project, CZI maintains a community for past and present cohort participants.
The conference is a chance to connect, learn and share among the passionate- and unique- community that is rare disease advocates. This year’s themes included fostering cross disease collaborations to improve research outcomes and ensuring patient organizations’ sustainability through cultivating staff and organizational infrastructure.
Collaboration with TNF Pharmaceuticals
We’re excited to share that the DADA2 Foundation is exploring a partnership with TNF Pharmaceuticals to launch a compassionate use study of a potential new treatment called Isomyosamine for DADA2 patients.
This program is designed to give access to Isomyosamine for patients who don’t have other treatment options, and their health continues to decline severely—especially when standard therapies haven’t worked or aren’t available.
This collaboration reflects our shared commitment to expanding access to potential treatments, and we are grateful to TNF Pharmaceuticals for helping advance care in this critical area. As soon as next steps and details are available that can help patients be considered for care, we will update our communities. Learn more at the link below.
New Clues About ADA2 in DADA2
While it’s well established that DADA2 is caused by low or absent levels of the ADA2 enzyme in the blood, the exact chain of events that leads to the disease’s wide range of symptoms remains unclear. The clinical presentation of DADA2 is complex suggesting that more than one biological pathway is involved. The more we learn about ADA2’s full role in the body, the better equipped we’ll be to find new treatments or even tailor treatments to each patient’s specific symptoms.
A growing body of research has expanded our understanding of ADA2 and its functions. While ADA2 was initially thought to act mainly in the bloodstream, helping to break down adenosine, it now appears to have a broader role, including within cells themselves.
One well-supported theory is that when ADA2 enzyme activity is missing from the blood, adenosine—a molecule involved in immune regulation—builds up outside cells. Excess adenosine can disrupt normal immune signaling and contribute to chronic inflammation or immune suppression. But that may only be part of the story.
Several recent studies have shown that ADA2 also accumulates inside lysosomes—small compartments in cells that break down waste and recycle materials. The exact function of ADA2 in lysosomes is still being explored, but this buildup may play a key role in disease progression. Notably, Dr. Lisa Ehlers and colleagues at KU Leuven found that certain compounds that interfere with lysosomal function can trigger the release of ADA2 from inside cells.
Adding to this evolving picture, a recent paper by Dr. Liang Dong and collaborators suggests that ADA2 also influences how immune cells called monocytes develop and respond to inflammation from within the cell. Specifically, higher levels of ADA2 inside monocytes were associated with their activation and readiness to respond to threats. This intracellular role implies that ADA2 helps “tune” the immune system from the inside out—far beyond its originally understood function in the bloodstream.
Together, these discoveries represent a major step forward in understanding ADA2’s complex role in health and disease—and offer promising new directions for treating DADA2 more effectively.
Featured Published Articles on DADA2
Hong Y. et al, Nature/Gene Therapy, 24 June 2025
Sara Signa et al, Journal of Clinical Immunology, 16 June 2025
Pietro Francesco Bica et al., Pediatric Rheumatology, 23 May 2025
Inhibition of lysosomal degradation increases expression of mutant ADA2 in DADA2 monocytes
Lisa Ehlers et al, Journal of Allergy and Clnical Immunology, 20 June 2025
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