PLATFORM & PIPELINE
Based on good will, we continuously strive to innovate science
and technology to improve the quality of life of patients and their families.
MOONSHOT은 인간이 달로 여행을 가는 상상을 도전을 통하여 현실화 시킨 것과 같이 인간의 미래를 바꿀 거대한 아이디어를 현실로 바꾼다는
의미입니다. 일리미스테라퓨틱스의 GAIA-Aβ는 기존 알츠하이머 치료제의 문제점인 ARIA를 개선함으로써 알츠하이머 질병으로 고통받는 환자와
그 가족들의 삶의 질을 개선할 수 있다는 희망을 현실화 시키기 위한 일리미스의 위대한 도전입니다.
GAIA-Aβ 논문 정보
Anti-inflammatory clearance of amyloid-β by a chimeric Gas6 fusion protein
Hyuncheol Jung, Se Young Lee, Seongjoon Lim, Hyeong Ryeol Choi, Yeseong Choi,
Minjin Kim, Segi Kim, Yujean Lee, Kyung Ho Han, Won-Suk Chung & Chan Hyuk Kim
Clearing amyloid-β (Aβ) through immunotherapy is one of the most promising therapeutic approaches to Alzheimer’s disease (AD).
Although several monoclonal antibodies against Aβ have been shown to substantially reduce Aβ burden in patients with AD, their effects on improving cognitive function remain marginal. In addition, a significant portion of patients treated with Aβ-targeting antibodies experience brain edema and microhemorrhage associated with antibody-mediated Fc receptor activation in the brain.
Here, we develop a phagocytosis inducer for Aβ consisting of a single-chain variable fragment of an Aβ-targeting monoclonal antibody fused with a truncated receptor binding domain of growth arrest-specific 6 (Gas6), a bridging molecule for the clearance of dead cells via TAM (TYRO3, AXL, and MERTK) receptors.
This chimeric fusion protein (αAβ–Gas6) selectively eliminates Aβ plaques through TAM receptor-dependent phagocytosis without inducing NF-kB-mediated inflammatory responses or reactive gliosis.
Furthermore, αAβ–Gas6 can induce synergistic clearance of Aβ by activating both microglial and astrocytic phagocytosis, resulting in better behavioral outcomes with substantially reduced synapse elimination and microhemorrhage in AD and cerebral amyloid angiopathy model mice compared with Aβ antibody treatment.
Our results suggest that αAβ–Gas6 could be a novel immunotherapeutic agent for AD that overcomes the side effects of conventional antibody therapy.