To mark World Down’s Syndrome Day on March 21, over fifty researchers from 13 countries [1] are calling for more resources to be devoted to research, and for the inclusion of affected people in clinical trials to be guaranteed.
Down syndrome: medical research, the primary driver for inclusion and innovationOn this March 21, 2025, initiatives are flourishing around the world to celebrate inclusion, welcoming of differences, continued defense of individual rights, and the promotion of well-being of people with Down syndrome. As international researchers, with expertise in this genetic condition, we are concerned that scientific advancements promoting the health of people with Down syndrome remain largely unknown and underfunded by the public. Yet, these discoveries hold the promise of a better future for a population that remains marginalized and underserved, and who is incredibly valuable citizens of our society.
Since the discovery of the genetic cause of Down syndrome, named trisomy of chromosome 21 (trisomy 21), in 1959 by Jérôme Lejeune, Marthe Gautier, and Raymond Turpin, the inclusion of people with Down syndrome in society has significantly improved. However, it is less well recognized that this progress has been closely linked to a remarkable increase in average life expectancy, which rose from just 9 years in the 1930’s to 20 years in the 1970’s and now approaches 60 years in some countries. This improvement is largely due to better management of co-occurring conditions frequently associated with Down syndrome – particularly cardiac, respiratory and endocrinological pathologies – thanks to positive progress in medical research and clinical care.
Medical research is therefore a catalyst for inclusion for individuals with Down syndrome. Could improving the intellectual disability associated with Down syndrome through drug treatments and/or other interventions be a reasonable expectation? Increasing evidence suggest this to be a possibility that could open up in the future. Indeed, the triplication of chromosome 21 leads to changes in the regulation of gene expression, even beyond genes located on chromosome 21 itself. The link between the excess of certain proteins and the clinical, developmental, and cognitive differences linked to Down syndrome is now well established. Targeted therapeutics counteracting the effects of gene overexpression have the potential to ameliorate the harmful effects of gene overdosage, which is the goal of several ongoing research projects. Never before has scientific research been advancing at such a rapid pace, with a multitude of clinical trials underway, offering unprecedented hope for new approaches. One example are multiple Phase II clinical trials testing the safety and efficacy of immunomodulatory therapies aiming to reverse the immune dysregulation and chronic autoinflammation caused by triplication of the interferon receptor genes (IFNRs) encoded on chromosome 21 (NCT04246372, NCT05662228). Other examples include development of inhibitors targeting CBS and DYRK1A gene products, which are also encoded on chromosome 21. The CBS project is currently in the pre-clinical phase, while the DYRK1A project is in the first phase of clinical trials (NCT06206824). Furthermore, another trial is testing the clinical efficacy of bumetanide, to improve memory and psychological functioning in children and adolescents (NCT06465823).The most effective solution will likely not be a single treatment. Over the long term, a combination of therapeutic approaches may work together to have the best possible impact on the cognitive abilities of individuals with Down syndrome. If successful, this could lead to a significant gain in autonomy for these individuals, transforming how society perceives intellectual disability.
When considering this perspective, the current obstacles to research, on the sociocultural and financial levels, clearly seem surmountable.
Culturally, Down syndrome-associated medical issues have often been viewed as a subject too complex to study. For decades, it was believed that there were no effective approaches for improving intellectual disability. Furthermore, due to concerns about ethics such as informed consent, intolerance to tests, or challenges in evaluating results, people with Down syndrome are often excluded from clinical studies on other pathologies, even though they may be more frequently affected. For instance, despite their significantly higher risk of developing Alzheimer’s disease, which is driven by the triplication of the amyloid-precursor protein (APP) encoded on chromosome 21, individuals with Down syndrome are often excluded from clinical trials for new treatments targeting Alzheimer’s disease. This exclusion is largely due to concerns about their elevated risk of cerebral amyloid angiopathy (CAA), a condition that increases the possibility of brain haemorrhages in response to certain therapies. However, these same risks affect the general population as well.
Investing in research to develop safer treatment strategies specifically tailored to individuals with Down syndrome could not only provide them with essential treatment options but also lead to advancements that improve the safety and efficacy of these therapies for everyone. The ABATE Study (NCT05462106) is currently testing a potential treatment for Alzheimer’s disease targeting the APP protein in people with Down syndrome and the Phase 1 results are promising. The HERO study (NCT06673069) is testing an antisense oligonucleotide (ASO) that APP. Furthermore, the upcoming ALADDIN study will evaluate the safety and efficacy of an FDA-approved anti-amyloid immunotherapy, specifically donanemab, for individuals with Down syndrome. All three trials are affiliated with the NIH-funded Alzheimer’s Clinical Trials Consortium – Down syndrome (ACTC-DS) which has enrolled participants across 21 international sites into the Trial Ready Cohort (TRC-DS) in efforts to bring the latest AD therapeutics to the DS community.
The desire to welcome individuals with Down syndrome for who they are can sometimes conflict with the ambition to find treatments to improve intellectual disability. Some argue that improving cognitive function may lead to the loss of their unique characteristics, viewing it as a form of discrimination. While this mindset is more prevalent in certain countries, it is not exclusive to them. Our vision, however, is different: we believe that medical innovation can uncover the hidden yet very real abilities within each person, allowing them to thrive without altering their fundamental identity. Financially, unconscious biases persist, with the belief that individuals with Down syndrome cannot be meaningfully integrated into society. In Europe, these biases contribute to a lack of collective will to fund research on Down syndrome, leaving individuals with Down syndrome as a medically underserved population even though this condition affects 1 in 700 births.
Funding for research on this genetic condition is marked by significant geographical disparities. In the United States, the National Institutes of Health (NIH) partnered with diverse organizations, including GLOBAL Down Syndrome Foundation, the Jerome-Lejeune Foundation, the Alzheimer’s Association, and the Trisomy 21 Research Society (T21RS), among the others, to form the Down Syndrome Consortium in 2011. Advocacy efforts, spearheaded by GLOBAL Down Syndrome Foundation, supported the launch in 2018 of the NIH’s INCLUDE Project, which has allocated > 400 million dollars to Down syndrome research until today. The INCLUDE Project support myriad basic science studies, many new cohort studies of Down syndrome, fifteen new clinical trials so far, and numerous training and career development grants. In the European Union, limited fundings has slowed progress and limited the number of breakthroughs in the field of Down syndrome research. That said, we must acknowledge the support of 12 million euros over 5 years for the ICOD project (Improving COgnition in Down syndrome, NCT05748405) and the GO-DS21 consortium (Gene Overdosage and comorbidities during the early lifetime in Down Syndrome) through the efforts of the Horizon 2020 program. Nonetheless, European funding for research on Down syndrome originates mainly from the generosity of private donors, notably via the Jérôme Lejeune Foundation, a major funder and incubator of research in Europe. In Asia, and in the global South, funding for such research is virtually non-existent.
How can this situation be addressed? Firstly, it is crucial to raise awareness about the benefits that research for people with Down syndrome can bring, not just to people with Down syndrome, but to society at large. For researchers and healthcare professionals, Down syndrome offers a unique opportunity to gain insights into other diseases, such as congenital heart disease, sleep apnea, autoimmune disorders, respiratory issues and Alzheimer’s disease, which are more prevalent in this population, and to develop new therapies that could benefit everyone. More broadly, research for people with Down syndrome is inherently interdisciplinary, spanning genetics, neuroscience, cardiology, immunology, endocrinology, and behavioral sciences, and serves as a powerful catalyst for innovation.
We see it every day: this field of medical research arouses great scientific curiosity, genuine passion and a strong desire to improve the lives of those affected. There is no doubt that, beyond the exciting potential outcomes, research for people with Down syndrome is a step toward achieving a more inclusive society. It provides opportunity for people with Down syndrome to feel fully engaged in a meaningful project as volunteers; it encourages them to express their needs and challenges, which may not always align with common perceptions; and it fosters collaboration among persons with Down syndrome, families, relatives, organizations and experts, with outcomes that extend far beyond the medical framework.
Funding research for people with Down syndrome is an investment in a future where individuals with Down syndrome are seen not only seen as beneficiaries, but also as essential contributors to scientific and social progress. To achieve this, we call on policymakers, funding organizations, and the scientific community to increase dedicated research funding, ensure the inclusion of individuals with Down syndrome in clinical trials, and foster interdisciplinary collaborations. This is not just a scientific imperative—it is a human one. The time to act is now.
[1] Eugenio Barone, Italy ; Renata Bartesaghi, Italy ; Laura Cancedda, Italy ; Filippo Caracin, Italy ; María Carmona-Iragui, Spain ; Cécile Cieuta-Walti, Canada ; Alberto Costa, United States ; Floriana Costanzo, Italy ; Alain Dekker, Netherlands ; Rafael de la Torre, Spain ; Fabio Di Domenico, Italy ; Mara Dierssen, Spain ; Joaquin Espinosa, United States ; Elizabeth Fisher, United Kingdom ; Juan Fortea, Spain ; Pilar Garcia, Spain ; Sujay Ghosh, India ; Ann-Charlotte Granholm, United States ; Sigan Hartley, United States ; Elizabeth Head, United States ; Pablo Helguera, Argentina ; Yann Herault, France ; Thessa Hilgenkamp, United States ; Jacqueline London, France ; Mariana Maccioni, Argentina ; Pierre-Yves Maillard, France ; Eimear McGlinchey, Ireland ; André Megarbane, Lebanon ; Laurent Meijer, France ; Clotilde Mircher, France ; Elliott Mufson, United States ; Lucio Nitsch, Italy ; Dean Nizetic, United Kingdom ; Eitan Okun, Israel ; Marzia Perluigi, Italy ; Jon Pierce, United States ; Marie-Claude Potier, France ; Michael S. Rafii, United States ; Diego Real de Asua, Spain ; Anne-Sophie Rebillat, France ; Damien Sanlaville, France ; Jonathan Santoro, United States ; Stephanie Santoro, United States ; Iris Scala, Italy ; Ignacio Sfaello, Argentina ; Brian Skotko, United States ; Fiorenza Stagni, Italy ; Pierluigi Strippoli, Italy ; Csaba Szabo, Switzerland ; Antonella Tramutola, Italy ; Rosa Anna Vacca, Italy ; Diletta Valentini, Italy ; Stefano Vicari, Italy ; Frances Wiseman, United Kingdom ; Bing Ye, United States ; Eugene Yu, United States ; Shahid Zaman, United Kingdom.
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