Protein biomarkers in rare diseases explored at Smith-Lemli-Opitz Syndrome Conference
In a recent presentation at the 2023 Smith-Lemli-Opitz Syndrome Scientific Conference, Stephanie Cologna, PhD, an Associate Professor at the University of Illinois at Chicago, discussed the discovery and translation of protein biomarkers for rare diseases. Her presentation shed light on the potential of biomarkers for drug discovery and approval in the context of rare diseases.
Dr. Cologna emphasized that protein biomarkers have often been overpromised and underdelivered in the past. However, she believes that rare diseases present unique opportunities for leveraging biomarkers in the fields of drug discovery and approval. Her research primarily focuses on the use of mass spectrometry and proteomics in the identification and validation of protein biomarkers.
One of the key aspects of Dr. Cologna’s work is the utilization of untargeted protein biomarker studies. She highlighted their workflow, which involves bottom-up proteomics and focuses on analyzing cerebrospinal fluid (CSF) in individuals affected by Smith-Lemli-Opitz syndrome (SLOS) compared to unaffected controls. CSF analysis is crucial as it allows researchers to gain insights into the brain’s biology in these individuals.
Through her studies, Dr. Cologna and her team have identified several proteins that exhibit alterations in patients with SLOS. Notably, a protein called “reelin” showed elevated levels in the CSF of individuals with SLOS. The significance of reelin lies in its involvement in neuronal migration, lamination, dendritic spine development, and synaptic function. However, validating these findings is a challenging process that requires further investigation, particularly in mouse models.
To validate the initial findings, Dr. Cologna’s team examined whole brain tissue in a mouse model of SLOS and observed a decrease in reelin levels, indicating a potential disruption in secretion or intracellular mechanisms. Additionally, they explored other biomarker candidates related to the DAB and SAP proteins, which demonstrated different expression patterns in the mouse model.
Despite the promising discoveries, Dr. Cologna acknowledged the limitations of her research, such as small sample sizes and relative quantification. Moving forward, she emphasized the need for targeted assays to better understand the biological and assay variants associated with these biomarkers. Furthermore, given the invasive nature of collecting CSF, she suggested exploring peripheral markers that could reflect brain changes through blood samples.
Her research offers valuable insights into the discovery and translation of biomarkers, paving the way for improved diagnostics, prognostics, patient stratification, and therapeutic efficacy evaluation in rare disease research and treatment.\
Cologna S. Protein biomarkers: From discovery to translation. Presented at: 2023 Smith-Lemli-Opitz Syndrome Scientific Conference.