Kajeno Asceneuron SA e phatlalatsa phatlalatso ea lintlha tse hlahlobiloeng ke lithaka koranteng ea ACS Chemical Neuroscience mabapi le ASN90, e leng O-GlcNAcase (OGA) inhibitor, le e 'ngoe ea likhetho tsa eona tse etelletseng pele ntlafatsong ea bongaka bakeng sa ho alafa neurodegenerative proteinopathies.
Neurodegenerative proteinopathies joalo ka lefu la Alzheimer's le Parkinson's li khetholloa ke ho thehoa ha intracellular bokong ba liprotheine tse sa qhibiliheng le tse chefo, joalo ka protheine ea tau e amanang le microtubule le α-synuclein ka ho latellana, tse amanang haholo le tsoelo-pele ea mafu. OGA ke sepheo se hlahang sa lithethefatsi molemong oa nts'etsopele ea lithethefatsi tsamaisong ea methapo e bohareng kaha khaello ea glycosylation ea liprotheine tsena tsa intracellular e amahanngoa le ho se sebetse hantle ha neuronal. Li-inhibitors tsa OGA li thibela ho felisoa ha liprotheine tsa intracellular glycosylation, ka hona li emisa ho theoha ha maemo a bophelo bo botle ba phetoho ena ea kamora phetolelo le ho thibela ho thehoa ha liprotheine tse chefo.
Ka pampiri e sa tsoa hatisoa, e hlahlojoang ke lithaka, Asceneuron e tlaleha ho sibolloa ha pele le nts'etsopele ea "molek'hule e nyane ea OGA inhibitor ASN90 (eo pele e neng e tsejoa e le ASN120290/ASN561), e seng e qetile liteko lithutong tse tharo tsa Mokhahlelo oa I lithutong tsa bacha le ba tsofetseng. . Lintlha tsa preclinical li bonts'a hore tsamaiso ea letsatsi le letsatsi ea ASN90 e thibetse nts'etsopele ea tau tangle pathology, hammoho le khaello ea ts'ebetso boitšoarong ba makoloi le phefumoloho, le ho phela ho eketsehileng. Tlhahiso e 'ngoe ea bohlokoa; buka ea sehlopha sena sa limolek'hule; ke hore ASN90 e liehile tsoelo-pele ea ho senyeha ha makoloi le ho fokotsa astrogliosis ka mokhoa o sebelisoang khafetsa, oa preclinical oa lefu la Parkinson.
Asceneuron hajoale e na le kopo e bulehileng ea sethethefatsi se secha sa lipatlisiso (IND) le US Food and Drug Association (FDA) bakeng sa boithuto ba Phase 2/3 ho lekola ASN90 in progressive supranuclear palsy (PSP), e leng sesupo sa khutsana. PSP ke boemo bo sa tloaelehang ba methapo ea kutlo bo bakang mathata a tebileng a ho tsamaea, ho leka-lekanya, puo, ho metsa le pono ka lebaka la ho bokellana ha liprotheine tsa tau bokong. Lefu lena le ntse le mpefala le ho feta, 'me batho ba holofala haholo nakong ea lilemo tse tharo ho isa ho tse hlano ho tloha ha le qala. Ho hakanngoa hore batho ba bararo ho isa ho ba tšeletseng ho ba 100,000 ba tla ba le PSP mme hajoale ha ho na pheko ea lefu lena.
Dirk Beher, Ofisiri e ka Sehloohong ea Phethahatso, Mothehi-'moho oa Asceneuron le sengoli se phahameng sa thuto, o itse: "Re thabile haholo ho phatlalatsa lintlha tsa bohlokoa tse khothatsang tsa pele ho ASN90 le mochini oa ts'ebetso oa OGA. Liphuputso tsena li fana ka mabaka a matla bakeng sa nts'etsopele ea li-inhibitors tsa OGA e le li-agent tse fetolang mafu ka bobeli tauopathies le α-synucleinopathies tse kang Alzheimer's, PSP, le lefu la Parkinson. Kaha li-pathologies tsa tau le α-synuclein li atisa ho ba teng mafung a amanang le neurodegenerative, li-inhibitors tsa OGA li emela batho ba ikhethang, ba sebelisang lithethefatsi tse ngata bakeng sa matšoao a mangata. Re ntse re tsoela pele ho nts'etsapele nts'etsopele ea rona ea bongaka ka OGA inhibitor ea morao-rao hang ka letsatsi, ASN51, e tla fuoa bakuli ba lefu la Alzheimer likhoeling tse tlang. ”
SEO U LOKELANG HO SE NKA HO SEHLOOHO ENA:
- 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.
