Treatment of Diseases Caused by Bacterial Exotoxins
Exotoxins and enterotoxins released by Staphyloccal aureus and Streptococcus pyogenes trigger massive release of inflammatory proteins (cytokines) by the immune system, which cause clinical problems in patients including: toxic shock syndrome; pulmonary infections causing pneumonia; severe atopic dermatitis and delayed wound healing. Left untreated, the body’s reaction to these toxins results in inflammation, microcapillary constriction, and eventually organ failure and death.
There are several treatments for these toxins and the reactions they cause, many involving antibiotic therapy; however, current treatments do not address inflammation associated with the toxins that remain at the site of the disease or infection. Furthermore, antibiotic-resistant strains of bacteria do not respond to antibiotic therapy.
The present technology provides a means to neutralize the toxins released by bacteria without the need for antibiotics as it binds tightly to the toxins and prevents the massive and sometimes fatal immune response.
Description/Details
The new technology is a small soluble protein (approximately 12,000 daltons), in which the engineered T-cell receptor variable beta-region has a high binding affinity for Staphyloccal enterotoxin B (SEB) and toxic shock syndrome toxin-1 (TSS-1), the two primary enzymes responsible for triggering toxic shock. This protein has been engineered to have a much greater affinity for these toxins compared with the body’s own T-cells. This allows the protein to block the body’s aggressive response to the presence of toxic shock related bacterial infections, neutralizing them and preventing a large inflammatory response.
Animal Model Test Results: When our modified T-cell receptor protein blocks the bacterial dual binding, it can be used to block the fatal chain reaction that leads to acute sepsis and septic shock. To confirm effectiveness, the inventor’s protein has been used to successfully prevent hypersensitivity to SEB in rabbits and has been demonstrated to prevent death and lesions in lung tissue in rabbits challenged with TSS or SEB.
Applications
SEB or TSS-1 neutralizing drug to treat or to provide therapy for, but not limited to, the following:
- Pulmonary infections (Animal data available);
- Wound healing (Animal data available);
- Toxic shock syndrome;
- Antibiotic resistant bacterial infections
Benefits
Affinity for sepsis-related toxins: The high affinity of the inventor’s protein makes it ideal as a comprehensive therapeutic, which requires relatively low doses to effectively neutralize the immune system’s fierce response to toxins.
Use in tandem with other treatments: Because modified T-cell receptors are a new therapy for the neutralization of septic shock, any treatment designed with this technology could be able to be administered in conjunction with existing pharmaceuticals, such as the now-common Xigris.