Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038379 (strabismus)
 9,317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since the introduction of botulinum toxin (BTX) as a therapeutic tool in the 1970s, the number of uses for this substance has increased exponentially. BTX's mechanism of action involves degrading the SNARE proteins blockading the release of acetylcholine into the neuromuscular junction. In many body systems, decrease of contractility, strength, and tension of certain muscle groups result in improved clinical outcomes. Applications now include cosmetic, gastroenterologic, otolaryngologic, genitourinary, neurologic, and dermatologic uses. In fact, BTX can be considered as a potential treatment in any situation involving inappropriate or exaggerated muscle contraction. Currently, the FDA has approved BTX-A (Botox) for treating glabellar lines, blepharospasm, strabismus, hemifacial spasm, cervical dystonia, and spasticity. With the addition of cosmetic applications to the FDA's approval list, the use of BTX has increased dramatically.
 ...
PMID:Noncosmetic uses of botulinum toxin. 1515 50

Clostridium botulinum neurotoxins (BoNTs) are effective therapeutics for a variety of neurological disorders, such as strabismus, blepharospam, hemificial spasm, and cervical dystonia, because of the toxin's tropism for neurons and specific cleavage of neuronal soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors (SNARE) proteins. Modifying BoNT to bind nonneuronal cells has been attempted to extend therapeutic applications. However, prerequisite to develop nonneuronal therapies requires the retargeting the catalytic activity of BoNTs to nonneuronal SNARE isoforms. Here, we reported the engineering of a BoNT derivative that cleaves SNAP23, a nonneuronal SNARE protein. SNAP23 mediates vesicle-plasma membrane fusion processes, including secretion of airway mucus, antibody, insulin, gastric acids, and ions. This mutated BoNT/E light chain LC/E(K(224)D) showed extended substrate specificity to cleave SNAP23, and the natural substrate, SNAP25, but not SNAP29 or SNAP47. Upon direct protein delivery into cultured human epithelial cells, LC/E(K(224)D) cleaved endogenous SNAP23, which inhibited secretion of mucin and IL-8. These studies show the feasibility of genetically modifying LCs to target a nonneuronal SNARE protein that extends therapeutic potential for treatment of human hypersecretion diseases.
 ...
PMID:Engineering botulinum neurotoxin to extend therapeutic intervention. 1948 72