This technology is a structural class of small molecule, transthyretin (TTR) ligands that can be used to simultaneously treat transthyretin amyloidosis (ATTR), such as wild-type transthyretin amyloidosis (ATTRwt), and ophthalmic conditions characterized by enhanced accumulation of lipofuscin in the retina, such as age-related macular degeneration (AMD).
AMD is the leading cause of blindness in developed countries, particularly in people older than 60 years. ATTRwt is a late-onset, non-genetic disease caused by accumulation of TTR amyloid deposits, mainly in the heart (ATTRwt-CM). Case reports and epidemiological studies support significant rates of AMD and ATTRwt-CM comorbidity, likely due to the high population frequency of both conditions in older individuals.
We previously developed a class of selective RBP4 antagonists as a potential therapy for dry ADM and Stargardt disease. While RBP4 antagonists can be an optimal treatment option for the majority of dry AMD patients, this class of drugs can be counter-indicated for a subset of individuals with genetic or age-related predisposition to ATTR. There is a significant medical need for a treatment for dry AMD without complications due to ATTR.
This technology is a structural class of transthyretin ligands capable of dissociating the RBP4-TTR complex to partially reduce the retinol traffic to the retina and thereby inhibit the formation of lipofuscin bisretinoids. The same ligand stabilizes the released TTR tetramer, thus preventing its dissociation to monomer and potential pathological aggregation. This class of TTR ligands may be effective at treating a host of macular degeneration diseases as well as TTR amyloidosis-based diseases. The technology may be used to treat uncomplicated forms of macular degeneration (such as dry AMD and Stargardt disease), as well as different genetic or sporadic forms of TTR amyloidosis not associated with macular degeneration.
Christopher Cioffi, Ph.D.
IR CU20308
Licensing Contact: Kristin Neuman