ELX‐02 is an investigational synthetic eukaryotic ribosome–selective glycoside optimized as a translational read‐through molecule that induces read through of nonsense mutations, resulting in normally localized full‐length functional proteins. ELX‐02 is being developed as a therapy for genetic diseases caused by nonsense mutations. Two phase 1a, randomized, double‐blind placebo‐controlled, single‐ascending‐dose studies were conducted in healthy human subjects to evaluate the safety and pharmacokinetics of ELX‐02. Single subcutaneously injected doses of ELX‐02 between 0.3 mg/kg and 7.5 mg/kg showed an acceptable safety profile without severe or serious drug‐related adverse events, including a lack of renal and ototoxicity events. Injection of ELX‐02 resulted in a rapid time to peak concentration and elimination phase, with complete elimination from the vascular compartment within 10 hours. ELX‐02 area under the concentration‐time curve to infinity showed dose‐exposure linearity (24‐fold increase for a 25‐fold dose increase), and the maximum concentration showed dose proportionality (17‐fold increase for a 25‐fold increase). The mean apparent volume of distribution was dose dependent, suggesting an increased distribution and tissue uptake of ELX‐02 at higher doses. The primary route of excretion was in the urine, with the majority of the compound excreted unchanged. These results support the evaluation of the safety, pharmacokinetics, and efficacy of repeat dosing in future studies.
Abstract. Choroideremia (CHM) is an x-linked recessive chorioretinal dystrophy, with 30% caused by nonsense mutations in the CHM gene resulting in an in-frame
Eloxx entwickelt wie PTC Therapeutics einen Wirkstoff, welcher in der Lage
ist Nonsene Mutationen zu überlesen.
Wieder mal etwas neues gefunden bzw. von 2009/2010,
aber bis dato noch nicht hier gelistet unter Publikationen.
Splice Site Mutations in the P-Cadherin Gene Underlie Hypotrichosis with Juvenile Macular Dystrophy
Der Fall eines damals 4 jährigen Mädchens aus Portugal ist nun publiziert.
Das Mädchen und deren Mutter sind persönlich bekannt und es besteht regelmäßiger Austausch.