Diseases of the central nervous system (CNS), particularly neurodegenerative diseases, present a host of unique challenges for biomarker development. For one, our most delicate organ is encased in the skull, making biopsy very difficult. Its blood-brain barrier membrane prevents not only drugs from entering but biomarkers from exiting the cortex. Furthermore, neurodegenerative disorders have very heterogeneous pathology, making knowing what to measure a difficult question.
Developing multimodal biomarkers for CNS disorders must address a number of limitations. Consensus and standardisation are vital to make sure that all parties in development are on the same page in terms of what is measured and how. This will allow for comparison between labs, trials, and beyond.
There needs to be a broader access to well characterised clinical samples; results will only be as good as the quality of the samples used. Rigorous replication and validation are also critical to address the quality of the biomarker that is being developed. To do so will require collaboration between data scientists and those with disease specific expertise. And finally, it is essential that the patient is centred in all of these discussions, understanding their needs and concerns.
One good example of a biomarker in the CNS is the neurofilament light chain (NFL). It’s a stable neuronal cytoskeleton protein released upon injury. The NFL can be detected in cerebrospinal fluid or in blood using various technologies. The NFL isn’t specific to any particular disease, so it is a great marker to combine with others. However, that does mean that detecting NFL will not tell the whole story about patient pathology.
This presentation also discussed HER-096, a small synthetic peptide currently being developed by Herantis Pharma for the treatment of Parkinson's disease. This innovative drug is designed for subcutaneous injections, offering a less invasive alternative to traditional intracranial therapies.
HER-096 has shown promising results in phase one clinical trials, demonstrating good safety, tolerability, and the ability to cross the blood-brain barrier. The drug works by modulating the unfolded protein response and ER stress within cells, which are crucial mechanisms in neurodegenerative diseases.
Preclinical studies have shown that HER-096 can protect dopamine neurons, reduce alpha-synuclein aggregation, and decrease neuroinflammation, ultimately improving motor symptoms in animal models. These findings suggest that HER-096 has the potential to be a disease-modifying therapy for Parkinson's disease, addressing multiple aspects of the disease's pathology.
