Longeveron Inc. (NASDAQ: LGVN) announced new data on its cellular therapy, Lomecel-B™, for mild Alzheimer's disease (AD) at the Clinical Trials on Alzheimer's Disease Conference (CTAD24). The findings suggest that Lomecel-B's inhibition of matrix metalloprotease 14 (MMP14) correlates with improved clinical and biomarker outcomes, offering potential insights into the treatment of this debilitating condition.
Targeting MMP14 in Alzheimer's Disease
The research presented at CTAD24 explored the role of MMP14 in Alzheimer's disease. Matrix metalloproteases are reportedly upregulated in AD, and the researchers hypothesized that excess MMP14 activity may contribute to AD pathogenesis by cleaving TIE2 (Tyrosine kinase with Immunoglobulin and Epidermal growth factor homology domains), a cell-surface tyrosine kinase receptor crucial for endothelial cell health and inflammatory responses.
Lomecel-B's Mechanism of Action
The study investigated whether Lomecel-B's capacity to inhibit MMP14 correlates with improved clinical and biomarker outcomes in mild AD. The researchers measured MMP14 inhibitory (MMP14i) activity, levels of TIMP2 (tissue inhibitor of metalloprotease 2), and VEGF-A (vascular endothelial growth factor-A) in Lomecel-B lots used in the CLEAR MIND trial.
Clinical Trial Data
Supernatant from Lomecel-B CLEAR MIND lots contained MMP14i activity, high levels of TIMP2 and VEGF-A protein. Patients receiving Lomecel-B lots with higher levels of MMP14i activity demonstrated enhanced responses vs. placebo on the composite Alzheimer’s disease score (CADS, the study secondary endpoint) than those who received low potency lots. Similar associations were evident with responses in the MoCA, ADCS-ADL, and left hippocampal volume. High MMP14i lots were also more effective in suppressing elevations in soluble (degraded) TIE2 in study patients, suggesting a potential role for MMP14i in AD treatment.
Implications for Alzheimer's Treatment
"As a medicinal signaling cell therapy that has multiple potential mechanisms of action to address inflammatory responses in the brain, Lomecel-B™ offers the potential to address the underlying pathology of Alzheimer’s disease," said Joshua Hare, M.D., Co-founder, Chief Science Officer, and Chairman at Longeveron. "This data adds to the positive clinical information from the Phase 2a CLEAR MIND clinical trial that showed Lomecel-B™ improved cognitive function, quality of life, and brain volume in the treatment of mild Alzheimer’s disease. We are very encouraged by the safety profile and efficacy evidence that support the differentiated therapeutic potential of Lomecel-B™ in Alzheimer’s disease."
The poster's conclusion stated, Together these findings suggest that ability to exert MMP14 inhibition may protect TIE2 receptor integrity and underlie, at least in part, the immunomodulatory and pro-vascular effects of Lomecel-B in mild AD. The findings offer potential mechanistic and clinical insights in the development of cellular-based therapy for AD.
Lomecel-B is currently being investigated for Alzheimer's disease, Aging-related Frailty, and hypoplastic left heart syndrome (HLHS).
