Research Overview
One of the key objectives of ROHHAD International Consortium is to bring together those working to advance ROHHAD knowledge and treatment with families and patients interested in being part of this research. Further, we hope that seeing what work is currently being done in ROHHAD will inspire and guide next steps for other investigators and research groups. Below you can find information about ROHHAD research currently being conducted by members of the ROHHAD IC.
The Tooth Fairy Project
Recent evidence has emerged suggesting that a small group of cells in the patient’s body known as neural crest cells may play a role in causing ROHHAD. Exciting recent advances have allowed neural crest cells to be collected from removed teeth (e.g., lost baby teeth or removed wisdom teeth). Recognizing the potential impact of this advance as a unique opportunity for ROHHAD research, we have aligned with one of the world’s leading experts in this technique (Dr. Larry Reiter). With this cutting-edge technology, we will have an accessible source of neural crest cells for ROHHAD research for the first time.
Co Project Lead: Dr. Larry Reiter, PhD
Co Project Lead: Dr. Debra E. Weese-Mayer, MD
The ROHHAD EPIGENETIC Project
Project Lead:
Dr Julie Harvengt, Clinical Geneticist
This project is dedicated to the epigenetic study of patients with ROHHAD Syndrome, in addition to their genomic analysis. The aim is to highlight regions of the genome that would show epigenetic alteration in ROHHAD patients.
The central dysregulations observed in the Syndrome are indicative of hypothalamic dysfunction. Understanding the underlying disturbances, such as the identification of an epigenetic mechanism, will allow progress in the understanding of physio-pathological mechanisms and biological pathways that could be targeted by a possible therapy
Link to further reading on the The ROHHAD EPIGENETIC Project here
The gene that causes ROHHAD
Scientists who are now studying ROHHAD previously discovered that mutations in a gene called PHOX2B cause a disorder named CCHS. This discovery allowed for earlier diagnosis, improved treatment, and clinical trials to improve outcomes in CCHS. ROHHAD and CCHS have many overlapping features, so these scientists hope to make a similar discovery in ROHHAD. The genes responsible for ROHHAD remain unknown right now, but genomic sequencing and other research tools are helping scientists investigate potential genes and biomarkers.
Contact Dr. Dattani and his team if you are interested in participation or learning more at M.Dattani@ucl.ac.uk
Project Lead: Professor Mehul Dattani MBBS DCH FRCPCH FRCP MD
Exploring ROHHAD through brain inflammation and hormones
Many reports in the medical literature indicate that patients with ROHHAD may exhibit nervous system inflammation and respond to treatments that suppress the immune system. In particular, researchers examining this potential neuro-immunological route have proposed ROHHAD might be a paraneoplastic inflammatory condition (one triggered by an abnormal immune system response to a cancerous tumor). Factors supporting this hypothesis include the presence of biomarkers found in other neuro-immune conditions in samples of ROHHAD patients, reports of inflammation in autopsy-derived brain tissue from patients who have succumbed to ROHHAD, clinical evidence of ROHHAD responding well to treatments that suppress the immune system, and similarities with another neuro-immunological disease called Opsoclonus Myoclonus Syndrome (OMS).
Project Lead: Dr. Leslie Benson, MD
ROHHAD syndrome has life-altering consequences for patients and their families due to its numerous complications, and mechanisms underlying the disease are still unknown. Consequently, our team is interested in studying whether an autoimmune attack on the nervous system may cause ROHHAD. In order to explore this hypothesis further, our team is collecting blood, spinal fluid, and tumor tissue.
International ROHHAD Registry
Project lead: Dr. Debra E. Weese-Mayer, MD
The Center for Autonomic Medicine in Pediatrics (CAMP) at Lurie Children's has collaborated with doctors from around the world to build the International ROHHAD Registry. Registries are tools researchers can use to capture important health data longitudinally (across ages and time) about certain populations. In ROHHAD, as in other rare diseases, low prevalence, lack of knowledge about the disease course, and phenotype heterogeneity hamper the development of drugs and other advances in care. The ROHHAD Registry was designed to overcome these limitations by playing a role in understanding the course of ROHHAD, and providing information necessary for clinical trial design. And, you can participate in this important project without leaving your home!
Link to further reading on this project and to learn how you can help.
The Hypothalamic cellular model project
Project Lead: Dr. Vidhu Thaker, MD
The hypothalamus is a central site for integration of information on many important functions such as appetite regulation, control of temperature and blood pressure and pituitary function. It is also important in making connections with the centers regulating breathing at a subconscious level. It is possible that abnormalities in hypothalamus lead to the features of ROHHAD syndrome. It is not possible to access the hypothalamus to assess this in humans during life. However, our lab has developed methods to make hypothalamic cells from the peripheral blood cells of humans. We are striving to use this method for children with ROHHAD syndrome and their unaffected parents. We collect peripheral white cells from the families, change them into pluripotent stem cells. We then culture these cells to generate hypothalamic neurons. We hope that comparing the neurons of affected children with their unaffected parents will help us define the changes or the pathways that lead to the clinical features of ROHHAD syndrome.
Link to further reading on this project and learn how you can participate.