|Category||Life Sciences and Biotechnology|
|Keywords||Peptide, Cytokine Storm, Inflammation, Sepsis, Wound Infections, Toxic Shock, Acute Respiratory Distress Syndrome|
|Current development stage||For Pharmaceutical development: TRL4 – PoC&Safety of candidate device or system is demonstrated in a defined lab or animal model|
The inflammatory response is essential for protective immunity, yet pathogens often elicit an excessive reaction known as a ‘cytokine storm’ that is harmful to the host and may result in multi-organ damage and in worst cases, death. Much has been published recently on cytokine storms within the context of the coronavirus pandemic. However, other medical conditions such as bacterial sepsis, severe wound infections, and toxic shock share that exaggerated inflammatory response. This problem is further compounded by the increasing incidence of multi-drug resistant strains.
The market of extreme inflammatory reactions is vast. There are ~ 27 million patients diagnosed with sepsis each year worldwide. In the United States, sepsis affects approximately 1.7 million adults each year and potentially contributes to more than 250,000 deaths. Various studies estimate that sepsis is present in 30% to 50% of hospitalizations that culminate in death.
Therapeutics targeting cytokine storm, sepsis, and other severe inflammatory responses are still lacking. In current clinical practice, neither the causative pathogen nor the specific cellular processes underlying deterioration of organ function can be assessed in a way that would allow tailoring of anti-infective or immunomodulatory therapies to specific patient needs. This is particularly relevant given the pressing need to respond within the first few “golden” hours. Indeed, there is an unmet need for novel treatment strategies that effectively subdue the cytokine storm yet leave host defenses intact.
The excessive inflammatory response underlying severe pathology is dependent on the interaction between two major players: B7 costimulatory receptors expressed on antigen-presenting cells (APC) and CD28 expressed on the T cell. The constitutively expressed B7-2/CD28 co-receptor pair plays a prominent role in the early course of an immune response, followed soon by induction of B7-1 that binds CD28 far more tightly.
Prof. Kaempfer’s lab has created incisive molecular tools that target the formation of the B7/CD28 costimulatory axis in the human inflammatory response. To attenuate the cytokine storm underlying infection pathology, yet preserve host defenses, they uniquely target the engagement of CD28 with its B7 co-ligands, by means of short peptides. Such peptides serve to attenuate, yet not to ablate, the host inflammatory response as a therapeutic strategy against cytokine storm and other pathologies involving excessive immune system activation. These host-oriented therapeutic peptides target the human inflammatory response, to control and prevent the cytokine storm, a strategy unlikely to be overcome by pathogen mutation. By attenuating, yet not eliminating, the pro-inflammatory signalling process, the peptides provide a selective approach that leaves a basal response intact, essential to enabling the elimination of the pathogen while avoiding side effects.
There is a growing unmet need for novel treatment of an extreme inflammatory response to infection. The global cytokine storm therapy market is poised to grow at a lucrative rate with the increasing incidence of multi-drug resistant bacterial strains, sepsis, surging viral diseases, inflammatory diseases such as pancreatitis, autoimmune diseases such as multiple sclerosis, and others, coupled with the escalating research, clinical development, and healthcare expenditures.
The proposed technology offers a novel strategy to attack inflammatory pathology by directly addressing the key molecular interaction underlying an exaggerated inflammatory response.