Realizing the therapeutic potential of LDL receptor biology
Our approach
LDL receptors, with robust genetic validation and deep biological validation, are high value therapeutic targets for the treatment of a variety of human diseases. Novoron has developed unique expertise, and a set of proprietary tools, enabling the development of therapeutics that target what has been a historically challenging receptor family. Our approach has demonstrated the ability to provide selective modulation of disease relevant physiology ,while sparing homestatic functions of these receptors.
LDLR family biology
Encyclopedia of Molecular Pharmacology ꟾ 705-708.
Historically, multiple attributes of the LDL receptor family have limited drug development efforts. Novoron’s technology overcomes these concerns in a variety of ways:
High Homology and Redundancy: Structural similarity within the receptor family, increasing the risk of off-target effects. – Attaining receptor selectivity enhances therapeutic index.
Complex Physiological Roles: LDLRss are involved in a variety of essential biological processes, so modulating their function can lead to undesireable adverse effects. – Precision modulation overcomes these concerns by leaving important biology intact.
Drugability Issues: LDLRs have historically been viewed as lacking clearly defined, drugable binding pockets. - Novoron’s unique target identification capabilities, structural modeling, and suite of discovery tools have enabled precision targeting of relevant receptor subdomains.”
Proteinopathies
LRP1 has been implicated as a central mediator of synaptic spread of proteins such as tau and alpha-synuclein. Disruption of LRP1 interactions with these proteins can prevent the prion-like spread of pathology, protecting against neurodegeneration and cognitive decline.
Neuroregeneration
In acute spinal cord injuries, tissue damage initiates signaling cascades, mediated by LRP1. that supress beneficial repair mechanism including myelination and neurite outgrowth. Attenuating LRP1 signalling locally disinhibits these critical pathways, stimultes regenrative capacity, and improves and neurological and autonomic function
LDLR drug discovery toolbox
Novoron has developed deep insights, and a proprietary suite of assays and tools and reagents that overcome historical drug development challenges in this target class. The key to exploiting the untapped potential of these receptors resides specifically target disease-relevant interactions while leaving important underlying biology intact.
