Protein Conjugates as Antimicrobial Drugs for Treating Infections in the Central Nervous System
The incidence of brain and central nervous system (CNS) infections is rising at an alarming rate, while treatment options remain very limited. Only about 5% of existing small-molecule medicines can cross the blood-brain barrier (BBB), and none of the currently approved protein therapeutics are capable of doing so. With increasing resistance of pathogens to common antibiotics and dire side effects of the immune system’s inflammatory response (frequently leading to brain abscess), CNS infections present doctors with a grave challenge. Clearly, there exists a significant and unmet need for novel biopharmaceuticals that can control CNS and brain infections in the most efficient way without eliciting an immune response from the patient. Dr. Kaltashov’s team has developed novel protein conjugates composed of covalently linked transferrin (a promising drug carrier than can cross the BBB) and lysozyme (an antibacterial enzyme that is not normally present in cerebrospinal fluid). These conjugates are designed to penetrate the BBB and combat Gram-positive bacterial infections of the brain and CNS while eliminating the risks and complications associated with conventional pharmaceutical treatments.
Targeted protein therapy, designed to cross the blood-brain barrier, can potentially treat Gram-positive bacterial infections of the brain and central nervous system (e.g., meningitis, encephalitis, brain abscess) that result from complications due to skull fractures, medical implants, untreated infections, or immune system compromise.
- Targeted protein therapy is designed to cross the blood-brain barrier to combat CNS and brain infections without inducing an immune response.
- Bacterial cell wall destruction by lysozyme means zero possibility for mutant bacterial resistance.
- Certain structural modifications of lysozyme can potentially allow for treatment of Gram-negative bacterial infections, broadly widening its applicability.
- Flexible linker molecule is engineered to allow conjugate to maintain high transferrin-receptor affinity and significant antimicrobial activity.