With Alzheimer’s disease becoming more prevalent by the day, it is essential the drug discovery and development industry refocus its efforts on new strategies to achieve much needed pharmaceutical breakthroughs.
During the last decade, drug development for Alzheimer’s has focused primarily on treating the disease and its symptoms. It’s time we step back and focus on discovering the cause of the disease and developing drugs that delay or, ideally, prevent the onset of the Alzheimer’s.
This shift is already in effect. Today, the world’s most prominent scientists are expanding their focus beyond amyloid and tau, both playing their roles in this devastating disease, to new strategies centered around detecting Alzheimer’s while it’s in the silent biological stage. Some groups are investigating cell stress, others are investigating brain inflammation, lipid metabolism, the importance of neurofilaments or small brain lesions. There are many promising mechanisms that could be ‘druggable;’ the focus is now on finding and testing more targets to determine how to prevent the onset of Alzheimer’s disease.
Ultimately, treating Alzheimer's will likely involve a combination of therapies. For example, it could mean treating amyloid and inflammation of the brain in parallel. It’s still early days for combination therapies; however, repurposing a known drug and combining it with a new drug is one strategy that may prove successful.
This is a strategy that has legs and promises even greater success as the industry receives approvals for medicines in other areas, such as for autoimmune diseases. Success with other drugs will open more doors for research in Alzheimer’s disease because we’ll have more new drugs to test as we explore new combination therapies.
Regardless of which new strategies are being explored, all new compounds must move from functional screening in vitro through in vivo and beyond. One of the biggest mistakes I see companies make as they work to advance compounds from in vitro to in vivo is testing models that aren’t closely aligned. This happens most often when companies use one partner to conduct in vitro studies and then use a different partner to conduct in vivo studies.
Working with a single CRO for early development is crucial because in vitro and follow-on in vivo studies can be designed using closely related models to, for instance, ensure the expressions of targets are the same.
The closer the in vitro model is to the in vivo model, the better the outcome. When in vitro studies are designed in a vacuum, it makes in vivo studies less predictable and the outcomes often suffer. Conversely, when companies choose a partner with proven animal models and cell models that match, the outcomes are better. For example, a mouse model expressing the same gene construct as the cell line ensures compounds are tested in in vitro and in vivo models with the same promoter, expressing the same protein fragment, with the same mutations, meaning ultimately with the same phenotype.
Fortunately, we’re seeing this shift to new strategies with the hundreds of small biotech companies focused on developing potential new CNS drugs and large pharmaceutical and biotech companies continuing to demonstrate commitment to developing disease-modifying treatments for Alzheimer's. We’re also witnessing a positive trend of more compounds moving to late-phase development as more companies choose to partner with a single high-quality CRO to ensure their in vitro and in vivo test models are closely aligned.
CRO Selection Checklist
Don’t underestimate the importance of CRO selection. CNS drug development is a high stakes job that requires a CRO partner that can help pharmaceutical and biotech companies overcome the challenges that arise when exploring new, innovative drug development strategies and taking compounds from functional screening in vitro through in vivo and beyond.
Use the CRO Selection Checklist below to help you vet CROs for your next CNS drug development project:
- Have deep experience in CNS disorders and decades of historical data to help guide your study.
- Have tested thousands of CNS compounds, with many of them moving to late-phase development.
- Have several Alzheimer's, Parkinson’s and other CNS disease models.
- Have models that are proven to work, as evidenced by moving compounds to the next phase.
- Excel at designing in vitro and follow-on in vivo studies using closely related models.
- Have experienced scientists doing the work.
- Have hands-on scientists who are available and equipped to make study design and testing recommendations.
- Ensure the same team of scientists follows the study from in vitro to in vivo, making recommendations such as the duration of treatment or which positive controls to use.
Birgit Hutter-Paier, Senior Director and Head of Neuropharmacology for QPS, established and managed the preclinical research group at QPS, which consists of highly experienced and professional members at associate and scientist levels. Hutter-Paier has extensive experience in life-science research and development, covering drug discovery and project management where she has directed multiple diverse and concurrent projects from early preclinical stage to pharmacology. During the last 15 years, her team at QPS has tested approximately 2,000 compounds specific to neurodegeneration and neuropathology, with nearly 50 of these compounds advancing to clinical development.