The Fulcrum product engine integrates insights from four scientific disciplines to identify novel drug targets and develop breakthrough medicines. The four disciplines are Gene Regulation, Human Genetics and Disease, Cell Biology, and Screening and Computation.
Genes are the fundamental units of biology. Over the last 20 years we have come to learn that the gene itself is rather static. The richness of biology emerges from the mechanisms that activate or repress these genes (turn them on or off). The collection of mechanisms that regulate the human genome is immense - epigenetics, transcription factors, enhancers, microRNAs and lncRNAs, among many others.
The ability to intervene in these gene regulatory mechanisms provides the basis of the target identification and validation engine at Fulcrum. Fulcrum is developing small molecule therapies that modulate these on and off switches of disease genes.
Genetics and Disease
The human genome provides the blueprint, or genetic code, for life. From the sequencing of the human genome we have gained an understanding of the genetic underpinnings of many diseases. This mechanistic understanding of disease enables a highly personalized approach to medicine. For each disease and for each patient we will pinpoint the genetic basis of disease and focus the Fulcrum product engine precisely on the diseases causative mechanism.
Advances in cell biology provide methods to model gene regulation in a human disease setting. This provides an efficient system for dissecting the mechanisms of gene regulation and characterizing disease pathology. These models enable our pursuit of therapeutic interventions.
Fulcrum works with cellular systems derived from patients themselves. In certain cases, these systems are cells donated by patients (in the example of a muscle biopsy). Or they can be obtained through the technology of induced pluripotent stem cells (IPSCs), which allows for the generation of multiple cell types from a single patient skin sample.
Screening and Computation
Advances in screening technology and computational methods allow for the efficient interrogation of gene regulatory mechanisms and the specific factors involved in the activation or repression of disease genes.
Genetic and chemical methods allow for the identification of gene regulatory mechanisms in cellular models of disease. Screening with these tools allows for the rapid identification of drug targets for the activation or repression of disease genes. Computational capabilities then allow for the analysis of big data sets to guide our product engine.
Collectively, the integration of these disciplines allows Fulcrum Therapeutics to develop new medicines for previously untreatable diseases.