Neurodegenerative diseases affect millions worldwide. Fifty million people are living with Alzheimer’s disease or other dementias. Although Alzheimer’s disease is one of the most recognized, it is just one of many neurological disorders, such as Multiple Sclerosis, Parkinson’s, or Huntington’s disease. These conditions lead to a gradual loss of neurons and brain function over time. The impact on a patient’s quality of life can be severe, with symptoms ranging from memory loss, tremors, to muscle weakness or dysfunction.
Although research has made progress during the last decade, clinicians are still facing the same challenge, i.e. the lack of markers for early disease detection before symptoms manifest. Even today, the diagnosis of Alzheimer’s disease can only be confirmed with 100% accuracy after the patient has passed away. Another important challenge is the lack of more pertinent biomarkers that can track disease progression. Such biomarkers are critical for the development and assessment of drug efficacy in clinical trials.
This and the complex nature of neurological diseases makes them very difficult to treat. Small molecule approaches, like peptides, have historically been prioritized as they may more easily cross the blood-brain barrier. Today, monoclonal antibodies, represent approximately one third of disease-modifying therapeutic approaches in development (Alzheimer’s Disease Drug Development Pipeline: 2022 (nih.gov), DOI: 10.1002/trc2.12295). Lecanemab, an antibody interfering with the formation of amyloid plaques, has been shown to reduce cognitive impairment and has recently gained accelerated FDA approval. Although this will not be the cure for Alzheimer’s disease, this is one of the very first DMT tackling the disease itself, by reducing amyloid levels in the brain, rather than only treating symptoms. However, this approach has several drawbacks, notably related to safety issues, with approx. 20% of treated patients developing oedema or microhemorrhages. Thus, emerging therapies such as gene and cell therapy, immunotherapy, as well as innovative approaches based on vaccines, are also being explored.
As the drug pipeline pushes forward with promising drug candidates, biomarkers are increasingly used both for the diagnosis and monitoring drug efficacy. Currently, the most promising biomarkers for diseases like Alzheimer’s, Parkinson’s, and other neurological disorders include canonical neurotoxic proteins, such as beta-amyloid, tau, alpha-synuclein, but also nonspecific biomarkers of neuronal death, such as neurofilament light chain (NfL), of inflammation, such as sTREM2 or GFAP and various others. Beta-amyloid and tau are particularly associated with Alzheimer’s disease, as beta-amyloid forms plaques in the brain, while tau forms tangles. The accumulation of these pathogenic forms of proteins is thought to play a role in the development of the disease. Similarly, alpha-synuclein is a biomarker associated with Parkinson’s disease, and its accumulation as oligomeric forms in the brain is also thought to contribute to the development of the disease. Neurofilament light chain is a biomarker associated with a range of neuronal diseases, like Multiple Sclerosis, in which this blood biomarker is predictive of disease progression and therapeutic efficacy. However, monitoring neurological biomarkers is not without challenges, as multiple forms and isoforms of these proteins exist, related to a specific group of diseases or stage in the onset of the disease. Current methods cannot differentiate between monomeric soluble and pathological oligomeric forms of these proteins, making it important to learn more about these pathological oligomeric forms of proteins. At Active, we are committed on one hand to staying on the cutting-edge of biomarker research and being on the lookout for innovative methods, and on the other hand to analyzing clinical samples for biomarkers related to neurotoxicity, neuronal damage, inflammatory processes, and blood-brain barrier integrity with validated methods in a controlled and regulated environment. By monitoring these biomarkers, we can provide a better picture of the impact of therapies on the progression of neurodegenerative diseases.
Identifying the right biomarker panel for a clinical study is a complex challenge, but it’s not the only hurdle. Obtaining the right matrix for analysis is also difficult. Currently, the gold standard for analyzing biomarkers related to neurodegenerative diseases is using CSF as a sample. While CSF has the highest concentration of some of these proteins, it’s the hardest sample to obtain, and many patients are reluctant to undergo the procedure. As a result, researchers are looking for less invasive alternatives, such as blood samples. Analyzing biomarkers in blood samples requires ultra-sensitive methodologies because the biomarker levels seeping into the bloodstream are much lower than in the brain or spinal cord. This technological advance has greatly contributed to our understanding of these diseases and our company has been at the forefront of providing ultra-sensitive solutions (MSD, Ella, Simoa) to pharmaceutical clients for analyzing circulating biomarkers in these pathologies.
Progress has been made in diagnosing and monitoring neurodegenerative diseases, but major challenges remain in this fast-moving field. Active is playing a key role in this journey, using its comprehensive expertise, technology, and workflow processes to provide reliable and validated methods to ensure that the data obtained is reliable. In addition, our team’s networks with clinicians and access to clinical samples is instrumental in our work in this field. By working together with sponsor partners and staying at the forefront of biomarker research, we are confident that we can continue to make strides in the fight against neurodegenerative diseases.
Join us in this journey at the upcoming AD/PD conference and let’s work towards a better future for patients! If you have any questions about these, or any of our other biomarkers, please fill out the form below and let us know!