I-Asceneuron SA namuhla imemezela ukushicilelwa kwedatha ebuyekezwe kontanga kujenali i-ACS Chemical Neuroscience ephathelene ne-ASN90, i-O-GlcNAcase (OGA) inhibitor, kanye nelinye lamakhandidethi ayo ahamba phambili ekuthuthukisweni komtholampilo ekwelapheni i-neurodegenerative proteinopathies.
I-Neurodegenerative proteinopathies njenge-Alzheimer's kanye nesifo sikaParkinson ibonakala ngokwakheka kwe-intracellular ebuchosheni bamaphrotheni angancibilikiyo futhi anobuthi, njenge-microtubule-associated protein tau kanye ne-α-synuclein ngokulandelana, axhumene kakhulu nokuqhubekela phambili kwesifo. I-OGA iyisidakamizwa esisafufusa esiqondiswe ekuthuthukisweni kwezidakamizwa ohlelweni lwezinzwa olumaphakathi njengoba ukuntuleka kwe-glycosylation kwalawa maprotheni angaphakathi kwamaseli kuhlotshaniswa nokungasebenzi kahle kwe-neuronal. Ama-OGA inhibitors avimbela ukuqedwa kwe-intracellular protein glycosylation, ngaleyo ndlela amise ukwehla kwamazinga esimo esinempilo salokhu kuguqulwa kwangemva kokuhumusha futhi avimbele ukwakheka kwamaphrotheni anobuthi.
Kuleli phepha elisanda kushicilelwa, elibuyekezwe ngontanga, i-Asceneuron ibika ukutholwa kwangaphambili nokuthuthukiswa kwenoveli encane ye-molecule i-OGA inhibitor ASN90 (ebiyaziwa ngokuthi i-ASN120290/ASN561), esesivele iphothule ukuhlolwa ezifundweni ezintathu zeSigaba I ezifundweni ezinempilo ezisencane nezabadala. . Idatha ye-preclinical ibonisa ukuthi ukuphathwa komlomo kwansuku zonke kwe-ASN90 kuvimbele ukukhula kwe-tau tangle pathology, kanye nokushoda kokusebenza kokuziphatha kwemoto nokuphefumula, kanye nokwanda kokusinda. Okunye okutholakele okubalulekile; inoveli yaleli klasi lama-molecule; ukuthi i-ASN90 yehlisa ukuqhubeka kokonakala kwezimoto futhi yehlisa i-astrogliosis esetshenziswa njalo, imodeli yangaphambi komtholampilo yesifo sika-Parkinson.
I-Asceneuron njengamanje inohlelo olusha oluvuliwe lophenyo lwesidakamizwa (IND) ne-US Food and Drug Association (FDA) locwaningo lweSigaba 2/3 ukuze luhlole i-ASN90 ku-progressive supranuclear palsy (PSP), inkomba yezintandane. I-PSP yisimo esingavamile sezinzwa esidala izinkinga ezinkulu zokuhamba, ukulinganisela, ukukhuluma, ukugwinya nokubona ngenxa yokunqwabelana kwamaphrotheni e-tau ebuchosheni. Lesi sifo siya ngokuba sibi kakhulu, lapho abantu bekhubazeka kakhulu phakathi neminyaka emithathu kuya kwemihlanu siqalile. Kulinganiselwa ukuthi abantu abathathu kuya kwabayisithupha kwabayi-100,000 XNUMX bazothuthukisa iPSP kanti okwamanje alikho ikhambi lalesi sifo.
U-Dirk Beher, Isikhulu Esiphezulu Esiphezulu, Umsunguli-munye we-Asceneuron kanye nombhali ophezulu wocwaningo, uphawule wathi: “Sijabule kakhulu ukushicilela imininingwane esemqoka ekhuthazayo enjalo ku-ASN90 kanye nendlela yokusebenza ye-OGA. Lokhu okutholakele kunikeza isizathu esiqinile sokuthuthukiswa kwama-OGA inhibitors njengama-ejenti aguqula izifo kukho kokubili i-tauopathies kanye ne-α-synucleinopathy njenge-Alzheimer's, PSP, kanye nesifo sika-Parkinson. Njengoba i-tau kanye ne-α-synuclein pathologies evame ukuba khona ezifweni ze-neurodeergenerative, ama-OGA inhibitors amelela abantu abahlukile, abamele izidakamizwa ze-multimodal ngezinkomba eziningi. Siyaqhubeka nokuthuthuka emtholampilo nge-OGA inhibitor yethu yakamuva, i-ASN51, ezonikezwa iziguli ze-Alzheimer's ezinyangeni ezizayo.”
LOKHO ONGAKUTHATHE KULESI SIHLOKO:
- Neurodegenerative proteinopathies such as Alzheimer’s and Parkinson’s disease are characterized by the intracellular formation in the brain of insoluble and toxic protein aggregates, such as the microtubule-associated protein tau and α-synuclein respectively, that are closely linked to disease progression.
- PSP is a rare neurological condition that causes severe problems with walking, balance, speech, swallowing and vision as a result of the accumulation of aggregates of the tau protein in the brain.
- In this recently published, peer-reviewed paper, Asceneuron reports the preclinical discovery and development of the novel small molecule OGA inhibitor ASN90 (formerly known as ASN120290/ASN561), which has already completed testing in three Phase I studies in healthy young and elderly subjects.
