Hoʻolaha ʻo Asceneuron SA i kēia lā i ka paʻi ʻana o ka ʻikepili i nānā ʻia e nā hoa ma ka puke pai ʻo ACS Chemical Neuroscience e pili ana iā ASN90, kahi mea hoʻopaneʻe O-GlcNAcase (OGA), a me kekahi o kāna mau moho alakaʻi i ka hoʻomohala lapaʻau no ka mālama ʻana i nā proteinopathies neurodegenerative.
ʻO nā neurodegenerative proteinopathies e like me ka maʻi Alzheimer a me ka maʻi Parkinson i hōʻike ʻia e ka hoʻokumu ʻia ʻana o ka intracellular i loko o ka lolo o nā ʻāpana protein insoluble a me nā mea ʻawaʻawa, e like me ka microtubule-associated protein tau a me α-synuclein pakahi, i pili pono i ka holomua o ka maʻi. ʻO OGA kahi lāʻau lapaʻau e puka mai ana i ka hoʻomohala ʻana i ka lāʻau lapaʻau ma waena o ka ʻōnaehana ma muli o ka nele o ka glycosylation o kēia mau protein intracellular i pili me ka neuronal dysfunction. ʻO nā mea hoʻopaneʻe OGA ke pale aku i ka hoʻopau ʻia ʻana o ka glycosylation protein intracellular, ma laila e hoʻōki ai i ka emi ʻana o nā pae kūlana olakino o kēia hoʻololi ma hope o ka unuhi ʻana a me ka pale ʻana i ka hoʻokumu ʻia ʻana o nā hui pūmua ʻona.
I loko o kēia pepa i paʻi ʻia e nā hoa, hōʻike ʻo Asceneuron i ka ʻike preclinical a me ka hoʻomohala ʻana o ka mole liʻiliʻi liʻiliʻi OGA inhibitor ASN90 (ʻike mua ʻia ʻo ASN120290/ASN561), ka mea i hoʻopau i ka hoʻāʻo ʻana i ʻekolu mau haʻawina Phase I i nā ʻōpio olakino a me nā poʻe ʻelemakule. . Hōʻike ka ʻikepili preclinical i ka hoʻokele waha waha o ASN90 i ka hoʻomohala ʻana o ka pathology tau tangle, a me nā hemahema hana i ka hana kaʻa a me ka hanu, a me ka hoʻonui ʻana i ke ola. ʻO kekahi ʻike koʻikoʻi; moʻolelo no kēia papa o nā mole; ʻO ia ka ASN90 i hoʻolōʻihi i ka piʻi ʻana o ka pōʻino kaʻa a hoʻemi i ka astrogliosis ma kahi hoʻohālike preclinical i hoʻohana pinepine ʻia o ka maʻi o Parkinson.
Loaʻa iā Asceneuron kahi noi lāʻau lapaʻau hou (IND) wehe ʻia me ka US Food and Drug Association (FDA) no kahi haʻawina Phase 2/3 e loiloi i ka ASN90 i ka holomua supranuclear palsy (PSP), kahi hōʻailona keiki makua ʻole. ʻO ka PSP kahi maʻi neurological kakaʻikahi e hoʻoulu ai i nā pilikia koʻikoʻi me ka hele ʻana, ke kaulike, ka ʻōlelo, ka ʻai ʻana a me ka ʻike ma muli o ka hōʻiliʻili ʻana o nā aggregates o ka protein tau i loko o ka lolo. Ke piʻi nui nei ka maʻi, me nā poʻe e lilo i ke kino kīnā i loko o ʻekolu a ʻelima mau makahiki o ka hoʻomaka ʻana. Ua manaʻo ʻia ʻekolu a ʻeono mau kānaka no ka 100,000 e hoʻomohala i ka PSP a ʻaʻohe lāʻau lapaʻau i kēia manawa.
Ua ʻōlelo ʻo Dirk Beher, Luna Nui, Co-Founder o Asceneuron a me ka mea kākau kiʻekiʻe o ka noiʻi: "Ua hauʻoli nui mākou i ka hoʻolaha ʻana i nā ʻikepili preclinical koʻikoʻi e pili ana i ka ASN90 a me ka ʻōnaehana OGA o ka hana. Hāʻawi kēia mau ʻike i kahi kumu kumu ikaika no ka hoʻomohala ʻana i nā mea hoʻopaneʻe OGA ma ke ʻano he mau mea hoʻololi i ka maʻi ma nā tauopathies a me α-synucleinopathies e like me Alzheimer, PSP, a me ka maʻi o Parkinson. Ma muli o ka hui pū ʻana o ka tau a me ka α-synuclein pathologies i nā maʻi neurodegenerative, ua hōʻike ʻo OGA inhibitors i nā moho lāʻau kūʻokoʻa, multimodal no nā hōʻailona he nui. Ke hoʻomau nei mākou i ka holomua o kā mākou hoʻomohala lapaʻau me kā mākou mea hou loa i ka lā OGA inhibitor, ASN51, e hoʻopaʻa ʻia i nā maʻi maʻi o Alzheimer i nā mahina e hiki mai ana.
He aha e lawe ʻia mai kēia ʻatikala:
- 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.
