Update from Ulysses Neuroscience Ltd. is an Irish SME that provides clinical and preclinical research services to pharmaceutical companies to accelerate their drug discovery programmes in neuropsychiatric and rare neurological disorders.
Ulysses has three core values which directly drive our research and interaction with pharmaceutical companies: Patient-Centricity, Translational Research and Social Responsibility.
The company specialises in fluid biomarker analysis in conjunction with existing clinical assessments as well as in preclinical transgenic and pharmacological models.
An overview of our current projects and patient-centric initiatives on paediatric rare neurodevelopmental diseases such as CDKL5 Deficiency Disorder and Fragile X Syndrome is provided below. Future projects on Angelman Syndrome and Rett Syndrome are currently under discussion and planning.

CDD is a rare neurodevelopmental disorder mainly affecting females caused by mutations of the Cdkl5 gene. It is characterized by early-onset seizures in the first months of life, intellectual disability, motor, sleep and social impairments. Currently, no therapies exist for CDD and patients are treated for temporary relief of the most disturbing symptomatology. The CDKL5 protein is apparently mainly expressed in the brain where modulates development and morphology of neuronal cells. The molecular basis for such defects is not clear but evidence suggests that it may depend on altered microtubule dynamics.

Microtubules are cytoskeletal elements playing vital roles in development of brain cells, supporting the formation, maintenance and remodelling of synapses, structures through which brain cells communicate. Dysfunction in microtubule dynamics leads to altered brain development and loss of synapses. Microtubule dynamics can be analyzed by measuring the post-translational modifications (PTMs) of the alpha-tubulin protein, the main building block of microtubules.

We have recently discovered that alpha-tubulin PTMs can be detected in peripheral fluids, such as blood plasma and cerebrospinal fluid (CSF) in both animals and humans. Pilot studies showed that behavioural alterations in Cdkl5 knock-out (KO; lacking the gene) mice were accompanied by changes in alpha-tubulin PTMs in the brain and plasma of Cdkl5-KO mice.

We have previously analysed plasma samples of patients from the US and Italy, and recruited patients from Ireland to expand the study. Our results showed a dysregulation of alpha-tubulin PTMs in CDD patients compared to controls. The study is now extended to recruit more participants in Italy to expand the sample size.

Update from Dr Omar Mamad  RCIS,

This study will help build strong foundations for potential new targets for the treatment of CDD, and will contribute to the effort of identifying good blood based clinical biomarkers of disease severity and progression.

This study is supported by the LouLou Foundation and internal Ulysses Neuroscience Ltd. funding.

As part of the FutureNeuro team in RCSI, led by Dr. Omar Mamad, we are investigating a rare neurodevelopmental disorder known as cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD). The CDD phenotype is characterised by early onset seizures, severe neurodevelopmental impairment, gross motor impairment, respiratory dysregulation and autistic features. There are more than 1,600 documented cases of CDD worldwide, however there is no cure or therapeutic treatment capable of ameliorating cognitive and behavioural symptoms as of yet. In collaboration with industry and charity foundation (HopeforHarper), we are studying the effect of new treatments (including protein substitution therapy and small molecules) in rescuing the CDD phenotype in preclinical models. Moreover, we are exploring the role of non-coding RNAs in CDKL5 gene expression funded by IRC-Entreprise and Epilepsy of Ireland. The regulation of non-coding RNAs provides an exciting potential treatment in CDD. The goal of our research is to improve our understanding of CDD and target the underlying causes of CDD to drive the development of advanced new precision therapies and improve the quality of life of patients