Drugs that Modulate Conserved Targets can be Multi-purposed
It is becoming clearer that conserved targets can be shared between diseases. Say for example, in case of TNF-alpha, this conserved target is shared between ALS, Crohn’s Disease, Rheumatoid Arthritis. Similarly, p53 is yet another attractive target that is shared among Cancer, Alzheimer’s, and Down Syndrome. So, there are opportunities for drugs that modulate conserved targets to be multipurposed. Here, we show a schematic representation of our inflammasome panel where, as you can see each well is targeted for a specific inflammatory disease. Therefore, by making use of a wide range of inducers, the pathophysiology of the diseases can be replicated. Different types of inducers can be used for creating a disease model, for instance, Imiquimod is a chemical mutagen that can be used for creating models of experimental Psoriasis. Whereas, for Vitiligo, a genetic mutation of the protein SLC45A2 is used. Hence, after the model is created, we validate it using clinical standards and end points.
Read Out: In here, in a single frame, we are capturing the disease progression across 24 related diseases. The light shade of grey indicates the rescue to a normal pathophysiology whereas the darker shade denotes the severity of the disease pathology. From this, we can see that the dexamethasone injection through IP, has returned the neutrophil migration rate to baseline in about 55% of the cases. As we can see, the anti-inflammatory nature of dexamethasone is highlighted in diseases such as Vitiligo and Crohn’s disease.
Clinical EndpointsIn here, all the clinical end points can be measured accurately which in turn provides a correlation of clinical trial. Therefore, based on the end point readouts from a range of diseases, we can assess the multi-purpose nature of the compound. Efficacy Map Since most of the inflammatory drugs have poor remission rate, the impact of the drug can be monitored for a period which will help in predicting the remission rate.