Researchers from Trinity recently hosted the first CDKL5-Ireland:Family Awareness Day at Science Gallery Dublin to raise awareness of CDKL5 – a rare brain developmental deficiency disorder.
The event also allowed the researchers to showcase work currently being undertaken at the Trinity College Institute of Neuroscience to diagnose and treat the disease, which was only recently identified. Trinity is the first institution in Ireland launching a research project on the disease.
The CDKL5-Ireland: Family Awareness Day proved to be very important for families of those with children living with the disease as it provided an opportunity for them to come together to share their experiences and gain support from one another. CDKL5 Ireland is an association of families affected by CDKL5 who are looking for support for their family members.
Speaking about the importance of the inaugural event, Principal Investigator Dr Massimiliano Bianchi from the Trinity College Institute of Neuroscience (TCIN), said: “CDD is a very severe disease in terms of symptomatology and the burden on the families is extremely important.”
“I have been working in the field of brain microtubule dynamics and synaptic plasticity for many years now and to see all this research having the potential to be of real help for patients is extremely rewarding. It is important to me that we had the opportunity to bring the Irish families affected by CDD together with the scientists here at Trinity so that we could interact and discuss the needs of these children. Discussing the symptoms of their children and the treatments that they believe to be more helpful with the families is indeed invaluable to point our research in the right direction.”
“I’d like to thank CDKL5 Ireland who have been an immense help and huge support throughout this whole process and particularly during the research grant application. I’m also grateful to the Lou Lou Foundation without whom this research would not be possible and for having been present at the event.”
Fiona Walsh, mum to Zoë, said: “I am excited that Trinity is undertaking Ireland’s first CDKL5 research project. There are 7,000 rare genetic disorders so we are grateful that the researchers decided CDKL5 was worthy of further study.”
Jonna Malone, mum to Maia, added: “I’m really happy with our event today. The turnout was great – we had four of our Irish CDKL5 families and a nice bunch of other supporters here together learning more about CDD and the research. Let’s hope this is only the first of many such events to come.”
CDKL5 Deficiency Disorder (CDD)
CDKL5 Deficiency Disorder (CDD) is a rare brain disorder caused by a mutation in the gene CDKL5 (cyclin-dependent kinase-like 5), which is located on the X chromosome. Most children affected by CDKL5 suffer from seizures that begin in the first few months of life and are unable to walk, talk or feed themselves. Many are confined to wheelchairs and are fully dependent on family for support.
Other symptoms of CDD include scoliosis, visual impairment, sensory issues and various gastrointestinal difficulties. Currently, no therapies exist for CDD and only symptomatic pharmacological treatments are available.
At present there are six patients in Ireland and one in Northern Ireland living with CDD.
Current research and its goals
Through their research, Principal Investigator Dr Max Bianchi from TCIN and his team hope to provide an early life diagnosis of the disease to provide immediate treatment aimed at correcting the neurodevelopmental alteration. Early identification of CDD accompanied by early therapeutic intervention will support patients and families living with the disease. The research may also lead to the discovery of innovative disease-modifying therapeutic interventions.
The CDKL5 gene provides instructions for making a protein that is essential for normal brain development. Little is known about the protein’s function, which acts to change the activity of other proteins, with researchers having not yet fully determined which proteins are targeted by the CDKL5 protein. Mutations in the gene lead to CDD.
The current study focuses on microtubules, which play a vital role in the development of brain cells and in supporting the formation, maintenance and remodelling of synapses, which brain cells use to communicate. Thus, dysfunction in microtubule dynamics leads to altered brain development and loss of synapses.
Previous studies at Trinity showed for the first time that alterations in brain microtubules are detectable in the plasma of patients affected by neurodegenerative disorders. More recently, and in collaboration with the University of Insubria (Italy), academics have observed in a preliminary study that behavioural alterations in a CDD animal model were accompanied by plasma changes of brain microtubules as well.
Importantly, those behavioural and microtubular changes were rescued by a pharmacological treatment with a specific microtubule modulator. Thus, the main objective of the study is to rapidly translate the data obtained in animals into patients by measuring brain microtubules in plasma of CDD patients sampled from Irish, Italian and US diseased cohorts.
Research Fellow at TCIN, Dr Omar Mamad, is working on the CDKL5 project at Trinity.
He said: “For me in particular this work is exciting, foremost because of its translational relevance and potential for clinical developments. Moreover I thoroughly enjoyed meeting many of the families affected by this condition at my first CDKL5-Ireland Family Awareness Day but also being part of the organisation of this event.”
“I am honoured to be among the scientists working on this CDD project. In addition to our clinical objectives and aims I hope our research will help patients and their families gain a greater understanding of the role CDKL5 plays in disease. Finally, it is of great importance to gain support from our society, research bodies and national funding which will help us realise our ambition in this novel field of research.”
Final-year student of Neuroscience at TCIN, Aoife Dempsey, added: “Medical research concerning rare diseases like CDD is often very slow-paced so, for me, having the opportunity to be involved in the early stages of research like this, which holds such ground-breaking potential, is an honour. I hope that we will soon see the day that effective treatment is available for every child born with CDD.”