World Rare Disease Day 2025 - Advancing Rare Disease Research Through Global Partnerships

Prof. Tipu Sultan, Paediatric Neurologist, The Children’s Hospital & University of Child Health Sciences, Lahore, Pakistan

What inspired you to focus your research on rare diseases, and what motivates you to continue in this field?

My patients certainly motivate me, especially rare disease patients those known as ultra-orphans, where the prevalence is so low, that there may be only hundreds to thousands of people in the world living with these diseases. These children come to us with their families looking to us for hope.

Can you share some of the most promising advancements in rare disease research that you’ve been involved with recently, particularly in collaboration with UCL?

Contributing to the genetic project of inherited glycosylphosphatidylinositol deficiency disorders (IGDs) whereby a number of affected individuals from our clinic were diagnosed with rare mutations in GPI deficiency genes and severe forms of epileptic developmental encephalopathy. Some of these children can now hope for improvement of their seizures with a vitamin B6 (pyridoxine) disease-specific treatment.

How has your collaboration with UCL contributed to your research, and what impact do you see it having on the rare disease community?

Our collaboration with the UCL neurogenetics team over the past 10 years has been an incredible journey. Together, we’ve discovered many new disease genes and explored potential solutions for rare neurological disorders. More importantly, we’ve been able to give hope to many families in Pakistan by providing genetic counselling and advocating for rare disease support at the policy level.

Prof. Maha Zaki, Professor of Clinical Genetics, National Research Centre, Cairo, Egypt

What inspired you to focus your research on rare diseases, and what motivates you to continue in this field?

Egypt is a highly populous country with a high rate of consanguinity. As a clinical geneticist since 1987, I have seen countless families suffering from genetic disorders, and I was determined to help them. This drive led me to focus on rare genetic diseases. Through working with these families over the years, we have discovered several new genes and rare disorders, contributions that have benefited patients, helped to advance science and guided other researchers in their efforts. 

Can you share some of the most promising advancements in rare disease research that you’ve been involved with recently, particularly in collaboration with UCL?

We established a very fruitful collaboration with UCL in 2018. Over the past seven years, this partnership has enabled us to bring advanced genetic testing to Egypt and jointly identify the genetic causes of many previously unsolved cases. For example, by combining our local expertise with UCL’s resources, we have uncovered new disease genes in Egyptian families, providing answers and relief to people who had gone years without a diagnosis. Each discovery not only brings hope to the affected family but also adds to the global knowledge of rare diseases.

What do you see as the biggest challenges in rare disease research today, and what steps can the scientific community take to address them?

The challenges in rare disease research are complex and pressing. The most significant issue is funding — the high cost of genetic diagnostics and research is difficult to meet, especially in developing countries like Egypt. Cutting-edge diagnostic tools and tests are essential, but they require significant investment and infrastructure. Moreover, research into treatments for rare diseases often remains underfunded because pharmaceutical companies tend to prioritize more common, commercially profitable conditions. We also face a shortage of expertise in this field, which means we must provide more training and exposure for clinicians and scientists. To address these challenges, we need greater global awareness, dedicated funding for rare disease work, and capacity-building in genetics and genomics.

An especially important outcome of my collaboration with UCL was the recent diagnosis of a patient with juvenile/early-onset Parkinson’s disease, achieved through the detection of a new PSMF1 gene variant. This breakthrough ended a 16-year diagnostic odyssey, allowing the patient to finally receive appropriate treatment, significantly improving their condition, quality of life, and their family’s well-being and hope for the future.

Additionally, the late-stage diagnosis of Sandhoff disease in a previously undiagnosed patient with severe developmental and epileptic encephalopathy was crucial. Identifying the genetic cause enabled carrier screening within the family, providing the opportunity for IVF with preimplantation genetic diagnosis (PGD) to help ensure a healthier pregnancy in the future.

What do you see as the biggest challenges in rare disease research today, and what steps can the scientific community take to address them?

The biggest challenge in rare disease research is achieving early and precise diagnosis, which is essential for personalized treatment. Many genetic disorders require intervention before birth or in early infancy to prevent irreversible damage, making newborn screening, preimplantation genetic diagnosis, and investment in gene therapy crucial. Bridging these gaps demands global collaboration, increased funding, and better integration of genetic services into healthcare systems.

How has your collaboration with UCL contributed to your research, and what impact do you see it having on the rare disease community?

For me, collaborating with UCL means never working alone. When I reach a dead end in diagnosis, I know there is a network of experts who can help—giving my patients hope and ensuring that every possible effort has been made. Beyond my own practice, this collaboration has helped establish new diagnostic pathways, meaning that future patients, even those not yet born, will benefit from the discoveries we make today. This is why this work matters.

Dr. Ehsan Ghayoor Karimiani, Consultant Medical Geneticist, Next Generation Genetic PolyClinic, Mashhad, Iran

What inspired you to focus your research on rare diseases, and what motivates you to continue in this field?

My journey into rare disease research began with a deep desire to bring answers and relief to families dealing with the unknowns of rare genetic disorders. What keeps me going is seeing the real-world impact of our work—how our discoveries can change patient care protocols and offer new hope to those who previously had none.

Can you share some of the most promising advancements in rare disease research that you’ve been involved with recently, particularly in collaboration with UCL?

Our collaboration with UCL has been incredibly fruitful, especially in enhancing the genetic diagnostics for families affected by rare conditions. Given the high incidence of consanguineous marriages in the Middle East, our work has not only increased the diagnostic yield but has also illuminated the genetic landscape of several unknown disorders. Together, we’ve embarked on joint research that is making strides in understanding and diagnosing these complex cases.

What do you see as the biggest challenges in rare disease research today, and what steps can the scientific community take to address them?

The road ahead is not without its hurdles. The complexity of rare diseases, coupled with sparse funding and data, poses significant challenges. We need to cultivate more global partnerships, boost funding for research, and improve our data sharing practices to build a more robust understanding of rare diseases worldwide.

I was inspired by the urgent need for better knowledge and resources for rare diseases in Kazakhstan. One of my primary goals has been to create a database of rare genetic mutations in the Kazakh population and make it accessible to clinicians and researchers in my country for future studies and epidemiological insights. I also aimed to identify the molecular causes of neurogenetic diseases in Kazakh families to improve diagnosis and develop better management strategies for our patients. Partnering with UCL has been instrumental in achieving these goals it has helped us establish long-term research collaborations between UCL and a network of neurology centres in Kazakhstan, facilitating student and researcher exchanges and greatly expanding our scientific capabilities.

Can you share some of the most promising advancements in rare disease research that you’ve been involved with recently, particularly in collaboration with UCL?

The most significant advancement has been the establishment of the UCL-Central Asia-Transcaucasia Disease Diversity Project, in which our centre is a key contributor. Through years of collaboration with UCL, we have identified the genetic causes of Parkinson’s disease, hereditary cerebellar ataxia, and chorea in Kazakhstan. Notably, as part of this project, the novel disease gene SPATA5L1 was first discovered in Kazakhstan.
In your opinion, what role does public awareness play in advancing rare disease research, and how can individuals contribute to supporting these efforts?                                   
Public awareness is very important for advancing rare disease research. In Kazakhstan, we do not yet have an established framework for public or patient involvement in research, but this is something I hope to develop. Increasing patient and public engagement can enhance research and improve healthcare outcomes by ensuring that the needs of those with rare diseases are heard. Individuals can help by educating themselves about rare conditions, supporting patient advocacy groups, and participating in awareness events. Even simple actions like sharing information and personal stories can reduce stigma and encourage authorities to support rare disease initiatives. 

Dr. Ulviyya Quliyeva, Neurologist, Mediclub hospital, Baku, Azerbaijan

What inspired you to focus your research on rare diseases, and how has your collaboration with UCL contributed to your work in this field?                                                     
Our collaboration with UCL began in 2019, and since then, over 600 families with rare neurological diseases have undergone genetic testing through whole exome sequencing. Each case has been carefully discussed with neurologists and geneticists from UCL, especially Dr. Rauan Kayirzhanov and Prof. Henry Houlden. In Azerbaijan, where consanguinity is common, and many genetic and metabolic diseases remain undiagnosed due to limited neonatal screening and lack of insurance coverage for genetic tests, the UCL-initiated SYNAPS project has been invaluable in helping diagnose affected families and providing hope for more accurate treatments.

Can you share some of the most promising advancements in rare disease research that you’ve been involved with recently, particularly in collaboration with UCL?                               
One of the most impactful advancements has been our research on the genetic landscape of Infantile Epileptic Spasm Syndrome (IESS), one of the most severe developmental and epileptic encephalopathies. This work, which evolved into a PhD thesis, uncovered treatable metabolic causes, novel mutations, and rare autosomal recessive diseases. These findings have expanded our understanding of the main etiologies of IESS in the Azerbaijani population and laid the groundwork for future screening programs and targeted therapies.

What are some of the biggest challenges in rare disease research, and how can global collaborations help overcome them?                                             
Studying rare diseases is challenging due to the limited number of cases and the lack of functional testing to assess the pathogenicity of newly discovered variants. Global collaborations with experienced institutions like UCL accelerate knowledge sharing, enable access to advanced technologies, and facilitate the exploration of unreported gene variants, ultimately driving research forward and improving patient outcomes.

Patient Engagement Spotlight – VAMP2 Community Perspective

For this segment, we spoke with Alexandra Gaudlap, founder of the Raging Raymond Foundation and the VAMP2 Rare Disease Community.

How has UCL’s research impacted families living with VAMP2-related disorders?

Research conducted at UCL has played a vital role in deepening our understanding of VAMP2-related disorders, which impact synaptic function and neurotransmitter release. Recent studies have identified both de novo and inherited mutations, providing crucial insights into developmental delays, epilepsy and movement disorders. While our families share many similarities, each experience is unique, and these discoveries have brought much-needed clarity to affected individuals, guiding them towards better care and support. Beyond diagnostics, this work strengthens advocacy, fosters global collaboration, and lays the groundwork for future therapeutic advancements.

What are the most critical unmet needs for your patient community that research could address in the coming years? 

One of the most pressing unmet needs in our community is understanding the symptoms of VAMP2-related disorders and identifying the most effective management strategies. While symptoms vary among patients, there are many overlapping challenges that we all seem to experience. Although our group would love a cure, we recognize that symptom management is a more realistic goal. However, we often feel left in the dark about the most effective approaches. We would love for the researchers to help bridge this gap by guiding evidence-based strategies for managing these symptoms.

What message would you like to share with researchers and the public about supporting rare disease initiatives?

As a VAMP2 community, we are not just numbers or data points or case studies, we are real families living with the daily challenges of this diagnosis, waking up each day not knowing what tomorrow may bring. Despite the uncertainty, we continue to fight - not because it's easy, but because our loved ones depend on us. We hope that other rare disease communities can look at our group and see that there are always ways to think outside the box to make a difference and that at the end of the day, one step forward is always better than one step backward.