Infigratynib jako nowa strategia leczenia przyczynowego achondroplazji- znaczenie wczesnej interwencji u dzieci
Keywords:
Achondroplazja, genetyka, Innowacyjne leczenie, infigratynib, wzrost kości, wczesna interwencja, FGFR3Synopsis
Achondroplazja (ACH) to najczęstsza postać dysplazji szkieletowej, spowodowana mutacją aktywującą w genie FGFR3. Choroba prowadzi do nieproporcjonalnego niskiego wzrostu, deformacji kostnych, powikłań neurologicznych oraz obniżenia jakości życia dzieci. Z powodu przyspieszonego kostnienia synchondroz i ich przedwczesnego zamykania się, interwencja terapeutyczna powinna być wdrożona możliwie jak najwcześniej, najlepiej tuż po urodzeniu. Celem pracy było omówienie roli wczesnego leczenia przyczynowego w achondroplazji oraz ocena potencjału terapeutycznego infigratynibu – doustnego inhibitora kinazy tyrozynowej FGFR1–3. Lek ten hamuje nadaktywność FGFR3 i normalizuje szlaki sygnałowe odpowiedzialne za wzrost chrząstki. Badania przedkliniczne wykazały, że infigratynib zwiększa długość kości długich oraz poprawia morfologię czaszki u myszy z achondroplazją. W badaniu fazy II PROPEL 2 u dzieci ≥5 lat leczonych wyższymi dawkami zaobserwowano istotny wzrost rocznej prędkości wzrostu (do 3,03 cm/rok), przy jednoczesnym zachowaniu korzystnego profilu bezpieczeństwa. Działania niepożądane miały łagodny i przemijający charakter. Achondroplazja znacząco obniża jakość życia chorych dzieci i ich rodzin, wpływając na funkcjonowanie fizyczne, społeczne i emocjonalne. Wdrożenie skutecznej terapii możliwej do zastosowania od okresu niemowlęcego może istotnie ograniczyć powikłania i poprawić rokowanie. Infigratynib wykazuje w tym zakresie duży potencjał, wymagający dalszych, długoterminowych badań klinicznych.
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Birth prevalence of achondroplasia: A systematic literature review and meta‐analysis. doi:10.1002/ajmg.a.61787
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June 19, 2025
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