ELPIS study brings hope to patients of rare genetic condition, CDD

Posted on: 30 July 2024

ELPIS is working to establish and validate a novel biomarker for CDD in mouse and human samples. ELPIS represents the first work of its kind for this rare and understudied disorder.

Biomarkers are important for early diagnosis, to monitor disease progression and to further understand underlying pathology of a disease.

CDKL5 deficiency disorder (CDD) is a rare genetic condition that results in the onset of infantile seizures as early as the first week of life and severe neurodevelopmental delay impacting cognitive, motor, speech, sleep patterns and visual function. In addition to brain related symptomatology, CDD patients present important gastrointestinal, musculoskeletal, and cardiovascular alterations. The disorder is due to mutations in the CDKL5 gene located on the X chromosome and mainly affects females, with an incidence of 1 in 40,000 to 60,000 newborns. There are currently no approved treatments to cure CDD patients.

The project is named ELPIS, inspired by the ancient Greek personification of hope, to symbolise the research team’s aspiration to bring hope to the global CDD community through understanding and treating this rare disorder.

Purpose of the ELPIS Study

Professor Massimiliano Bianchi,Founder / President & CEO of Ulysses Neuroscience started working on CDD following the award of a CDKL5 Program of Excellence Pilot Grant award to his team by the LouLou Foundation in 2019. This award funded work to establish and validate a novel peripheral biomarker for CDD in mouse and human samples, the first work of its kind for this rare and understudied disorder. In the subsequent years, the Loulou Foundation has provided continuous support totaling over US$600,000 to Prof. M. Bianchi and his Ulysses Neuroscience team, through both continuation and directed research funding mechanisms, to validate this biomarker in pre-clinical gene therapy models, as well in expanded validation in a larger cohort of patient samples from Ireland and Italy.

Just this month, the Loulou Foundation has announced an additional award of nearly $584,000 to extend and expand this project to assess additional candidate biomarkers, with biosample collection now expanded to Spain, Portugal, France, Germany, and Brazil.

The Ulysses Neuroscience Team

Objectives of the ELPIS study

• Plasma microtubule proteins: Microtubules are cylindrical filaments that maintain neuron structure and play a critical role in the ability of neurons to form connections in the brain, a process termed synaptic plasticity. Synaptic plasticity is particularly critical during early development and maturation of the central nervous system. Ulysses Neuroscience developed protocols to measure microtubule function in the plasma. The team’s initial results in CDD patients indicate disruption of microtubule function, suggesting impairment of neuronal plasticity and abnormal neurodevelopment.
• Additional neurological plasma biomarkers: The team’s initial results of neurological markers include decreased levels of brain derived neurotrophic factor (BDNF), a prevalent growth factor essential for the development of the CNS and for neuronal plasticity, and higher levels of neurofilament light (NfL), indicating potential neuronal damage.

The described biomarkers are important for early diagnosis and to monitor disease progression and to further understand underlying pathology of the disease. Use of the biomarkers has the potential to facilitate development of not only symptomatic, but more importantly disease modifying therapeutics.

Future plans for the team include collaboration with pharmaceutical companies to promote the use of the biomarkers investigated by ELPIS with the goal of advancing clinical trials on investigational therapeutics that are critical for CDD patients.

Professor M. Bianchi, Founder / President & CEO of Ulysses Neuroscience said:

 “I am extremely happy to announce the initiation of the ELPIS project, expanding globally our efforts to validate plasma biomarkers for CDD. The project embodies our hope and dedication to combating CDD together with the patient community. Thanks to the generous support from the Loulou Foundation, this award will enable us to explore additional biomarkers and extend our research to different European countries and, for the first time, to South America. We are committed to the patient community and to pioneering breakthroughs that will improve the lives of those affected by this rare and understudied disorder.”

Dan Lavery, CSO of the Loulou Foundation said:

“The Loulou Foundation is honored to expand our collaboration on CDKL5 Deficiency Disorder with Dr Bianchi and his talented team of scientists at Ulysses Neuroscience. Since 2019, we have worked with Ulysses on discovery and validation of biomarkers for CDD, to support the clinical development of novel therapeutics, as well as to better understand the disease itself.  The Ulysses team has worked closely with CDD patient groups around the world, partnering with them as equal collaborators in this fight to develop better treatments, and eventual cures, for this devastating condition.”

Further information: you can visit the Ulysses Neuroscience website for more information HERE.

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