Traditional drug discovery relies on the identification of a target, typically an enzyme or receptor, where it is hoped that binding to the target will elicit a desired biological response. Hundreds of thousands of compounds are tested for target binding through high throughput screening. However, this approach has typically taken 10-15 years with a cost of about $1.3 billion per successful drug launch. These enormous costs are due to high attrition rates of preclinical candidates because of lack of efficacy or unexpected safety concerns in clinical trials.
Fluorescent images of human neuronal cells, typically used in screening for new drugs.
PharmaKure’s solution to this development challenge is to screen molecules that have already been through some degree of clinical development in order to discover novel activities in other diseases. This ‘repositioning’ of existing or old drugs for new targets has the following advantages:
CynapseDx has been developing products to isolate proteins or cells from whole blood since 2012.
At the heart of our techniques is an antibody coated large ultra-dense magnetic particle that can force its way through the viscous, cell-rich media of blood to encounter and bind proteins. These can be free in plasma, or cell-associated.
Our primary focus is neurodegenerative diseases, such as Parkinson’s or Alzheimer’s Disease. Previous attempts to develop blood tests for these diseases have been unsuccessful, partly due to uncertainty over which biomarkers to choose and the likely scenario that there are only very low numbers of target proteins circulating in the blood stream. We have chosen to focus on oligomeric and aggregated forms of protein biomarkers and have demonstrated that our assays can measure these forms of biomarker proteins when testing real patient blood samples.
The drug repositioning or repurposing strategy has already led to several blockbuster drugs, for example, Viagra, which was initially intended to treat pulmonary hypertension, but has since been used to treat erectile dysfunction; and Rogaine which was intended to treat high blood pressure has been subsequently repositioned for treatment of hair loss and promotion of hair re-growth. Up to 2011, 34 reports were published where groups screened libraries of FDA approved drugs against various whole cell or target assays. None were for Alzheimer’s disease. Each screen identified at least one compound with a novel bioactivity.
In addition, rather than seeing if compounds bind to a single target, one of our strategies is to measure activities in cell culture. This gives a much larger range of targets, thus increasing the chances of success.
Ekins, S., and Williams, A. J. (2011) Finding Promiscuous Old Drugs for New Uses, Pharm. Res. 28, 1785-1791.