Abstract | BoNT je egzotoksin kojeg proizvodi gram pozitivna, anaerobna bakterija Clostridium
botulinum koja se prirodno nalazi u tlu, vodi, biljkama te probavnom traktu životinja (17). 1895.
godine belgijski mikrobiolog Emile Pierre Marie van Ermengem otkrio je BoNT koji je do tada
bio uzročnik velike smrtnosti diljem svijeta. Na mogućnost korištenja ovog toksina u terapijske
svrhe prvi je ukazao liječnik, Alan Scott, koji je 1973. proveo studiju na miševima i tako
dokazao djelotvornost botulinum toksina u liječenju strabizma. 1989. godine FDA izdaje
dopuštenje za primjenu BoNT-a u liječenju strabizma i blefarospazma čime je to postao prvi
toksin odobren za primjenu u terapijske svrhe (3).
Do danas je poznato sedam serotipova BoNT-a koji se označavaju slovima A-G. Mehanizam
njegovog djelovanja temelji se na blokadi otpuštanja neurotransmitera acetilkolina kroz
presinaptičku membranu, a to se postiže cijepanjem SNARE proteina koji su nužni u njegovoj
egzocitozi. Takav slijed događaja rezultira paralizom zahvaćenih mišića (11, 12).
Danas je spektar indikacija za primjenu ovog toksina značajno proširen i u konstantnom
porastu. Primjenjuje se u brojnim stanjima orofacijalne regije uključujući paralizu lica, u
liječenju migrene, trigeminalne neuralgije, trizmusa i TMP-a, dok ga doktori dentalne medicine
primjenjuju za tretiranje gummy smile-a, sijaloreje, kao dopunu ortodontskoj i implantološkoj
terapiji te mnogim kozmetičkim tretmanima. Važno je napomenuti da su određene indikacije
službeno odobrene, ali se BoNT primjenjuje i izvan tih indikacija (eng. off-label use) (8, 16). |
Abstract (english) | BoNT is an exotoxin that is produced by gram-positive, anaerobic bacterium Clostridium
botulinum, naturally found in soil, water, plants, and gastrointestinal tract of animals (17). It
was first discovered by Belgian microbiologist Emile Pierre Marie van Ermengem, who
concluded that it is a causive agent of, until then known as a very common and deadly
disease, botulism. The possibility of using this toxin for therapeutic purposes was first
proposed by doctor Alan Scott, while conducting experiments on mice and proving its
effectiveness in treating strabismus. In 1989, the United States Food and Drug Administration
issued a permission to use BoNT in treatments for strabismus and blepharospasm, making it
the first toxin to be approved for therapeutic purposes (3).
To date, seven serotypes of BoNT have been known, which are denoted by the letters A-G.
The mechanism of its action is based on blocking the release of neurotransmitter acetylcholine
through the presynaptic membrane, which is achieved by the cleavage of SNARE proteins
that are necessary for its exocytosis. Such sequence of events results in the paralysis of the
affected muscles (11, 12).
The spectrum of indications in which BoNT is used is significantly larger today and it is
constantly increasing. It is used in numerous conditions of the orofacial region, including
facial paralysis, treatment of migraine, trigeminal neuralgia, trismus and TMD, while doctors
of dental medicine use it to treat gummy smile, sialorrhea, as additional therapy in
orthodontics and implantology and in numerous cosmetic treatments. It is important to note
that certain indications have been officially approved, however BoNT is also known to be
used outside those recommended indications (off-label use) (8, 16). |