Brain-permeable sappα enhancer (DDL-110) for multiple sclerosis therapy
DDL-110 is a novel, orally bioavailable, brain-permeable small molecule that enhances soluble amyloid precursor protein alpha (sAPPα) to promote re-myelination in Multiple Sclerosis. UCLA's Drug Discovery Lab has completed extensive IND-enabling studies and GMP API preparation, enabling immediate in vivo testing in demyelination models for this high-unmet-need therapeutic.
Overview
DDL-110 is a novel small molecule therapeutic candidate developed by UCLA's Drug Discovery Lab for Multiple Sclerosis (MS). The compound works by enhancing soluble amyloid precursor protein alpha (sAPPα), a protein that supports differentiation and function of oligodendroglial precursor cells (OPCs), which are responsible for re-myelinating damaged axons. By addressing demyelination, a key therapeutic target in MS, DDL-110 offers a new approach to restoring neural function. Unlike direct sAPPα protein delivery, DDL-110 is an orally bioavailable, brain-permeable small molecule that significantly increases brain sAPPα levels, overcoming major delivery challenges.
Technical specifications
Key features:
- More potent analog of initial sAPPα-enhancing hit F03, with greater in vivo exposure in mice after oral treatment
- Excellent solubility, oral bioavailability, and blood-brain barrier permeability
- Significantly increases sAPPα in vitro in SH-SY5Y human neuroblastoma and CHO-7W cells
- Restores working memory to non-transgenic littermate levels in aged Alzheimer's disease mouse models
- Completed IND-enabling non-GLP and GLP studies including pharmacokinetics, receptor panel interaction, plasma protein binding, CYP450 inhibition/induction, metabolite identification, microsomal intrinsic clearance, cytotoxicity, rat toxicity, hERG, and dog dose escalation studies
- GMP API preparation completed
- Proposed validation in cuprizone demyelination model with motor function assessment, oxidative stress product quantification, myelin basic protein expression analysis, OPC counts, and axon thickness measurements
Technology readiness level
DDL-110 is at an advanced preclinical stage of development. The compound has completed extensive IND-enabling studies and GMP API preparation, positioning it for immediate in vivo efficacy testing in demyelination models. Sufficient material is in hand to perform studies in the murine cuprizone model of demyelination, with proposed assessment of motor function, biochemical markers, and histological endpoints. This advanced preclinical package enables rapid progression toward clinical development for MS, a disease with significant unmet therapeutic need for re-myelinating agents.
About University of California, Los Angeles
The University of California, Los Angeles is a comprehensive public research university anchored in a global city and serving a large, diverse student body. Industry engages through an integrated academic health system that enables clinical research and translation, extensive shared instrumentation and cleanrooms, and co‑located labs that support prototyping. A new research and technology park and proximity to Southern California’s innovation economy provide convenient pathways for collaboration, sponsored projects, and access to talent. Campus research is supported by competitive federal funding from agencies such as NIH, NSF, DOE, and the Department of Defense. A dedicated technology transfer office streamlines IP protection, licensing, industry‑sponsored research, and startup incubation.
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