Figure A indicates in rats the latency as a measure of time to escape from a maze. Figure B indicates AD rats with PRAM therapeutic showed less time to escape the maze, demonstrating improved memory and spatial recall
Invention Summary:
Alzheimer’s disease (AD) affects over 55 million people worldwide and is projected to triple by 2050. Current FDA approved treatments such as cholinesterase inhibitors and amyloid targeting therapies provide modest symptomatic benefits without meaningfully altering disease progression or addressing the full spectrum of the disease pathology. Up to 90% of individuals with AD exhibit non-cognitive symptoms such as depression, apathy and circadian rhythm discrepancies, where these symptoms negatively impact quality of life. AD neural substrates include beta-amyloid and phosphorylated tau deposition, neurofibrillary tangle (NFT) formation, neuroinflammation, and neurodegeneration. Locus coeruleus (LC), a widely projecting brain stem nucleus linked to arousal, memory, motivation, and other cognitive processes, is the earliest brain area to exhibit NFT depositions and degeneration. This degeneration of LC is linked with cognitive decline. Recently, therapeutic strategies in preclinical and clinical studies have targeted preserving or restoring LC functions.
Rutgers researchers have developed a novel gene-based method to treat cognitive decline associated with Alzheimer’s Disease. It utilizes the Photic Regulation of Arousal and Mood (PRAM) pathway, a retina-to-LC circuit identified in prior tract-tracing studies. With this technology, researchers can precisely activate the PRAM pathway using chemogenetic stimulation of the LC via Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) expressed in the retina. Our research shows that this approach improves learning, memory and behavioral flexibility deficits in an animal model of AD based upon inclusion of prominent human AD genes. This technology’s mechanism of action precisely activates the LC and related systems, functioning as a minimally invasive form of neuromodulation delivered through retinal tissue. This approach could benefit Alzheimer’s disease symptoms such as sleep disturbances, memory loss, apathy, and depression. In our studies, PRAM activation has been associated with improved memory as well as more precise spatial recall and learning. Retinal-based activation of the PRAM pathway therefore modulates LC function and may enhance cognitive outcomes in AD.
Market Applications:
PRAM methodology could be used for neurological and psychiatric treatments that involve locus coeruleus, as treatments for circadian disorders, depression, memory loss and a host of other disorders.
A treatment for early signs of Alzheimer’s Disease as well as management of later stage AD.
Advantages:
Approach is selective as it targets specific retinal cells without impeding vision.
Demonstrated efficacy in rat models.
PRAM pathway is a way to address early onset of AD rather than only downstream disease progression.
Utilized as a treatment in regulating circadian dysfunctions that include sleep disturbances, apathy and depression
Intellectual Property & Development Status: Issued Nationalized PCT application US, Australia, Canada, Japan, European Union Patent Convention. Available for licensing and/or research collaboration. For any business development and other collaborative partnerships, contact marketingbd@research.rutgers.edu.