Phosphoinositide modulation for treatment of neurodegenerative diseases

This technology is a set of drug targets that modulate phosphoinositide lipids and amyloid-b levels to treat Alzheimers disease. Unmet Need: Treatment for neurodegenerative diseases Current methods to treat neurodegenerative diseases such as Alzheimers disease target symptoms but do not address the underlying disease mechanism. The accumulation of amyloid β-peptide (Aβ) plaques is hypothesized to lead to neuronal injury and neurofibrillary tangles, so inhibiting Ab biogenesis or accumulation could treat neurodegenerative diseases characterized by this accumulation. Although this class of lipids is important, no FDA-approved neurodegenerative disease treatments target Aβ biogenesis or their interaction with phosphoinositide lipids directly. The Technology: Methods of modulating phosphoinositides to treat amyloid β related disease This technology is a method for treating neurodegenerative diseases that are associated with increased levels of amyloid beta. Select agents that inhibit the toxic effects of amyloid oligomers by increasing intracellular levels of phosphoinositol 4-phosphate and/or phosphotidylinositol 4,5-biphosphate can be used as potential therapeutics. By altering the lipid metabolism of Ab, these therapeutics can provide potential effective treatments for various neurodegenerative diseases, such as Alzheimers disease. This technology has been validated in mouse neurons, including ES-derived neurons. Applications: Treatment of Alzheimers disease Treatment of Parkinsons disease, Down Syndrome, and other neurodegenerative diseases Screening of Ab biogenesis levels Drug screening Screening of targets to boost neural phosphoinositide levels Prevention of Alzheimers disease and other neurodegenerative diseases Research tool for studying Ab and phosphoinositide lipid pathways in vivo Advantages: Boosts synthesis of compounds to potentially stop or reverse Alzheimers progression Applies to any Ab-induced neurodegenerative disease Treats Ab accumulation-induced cellular damage Multiple drugable targets in the same pathway Multiple assays for studying the effects Lead Inventor: Tae-Wan Kim, Ph.D. Patent Information: Patent Status Related Publications: Berman DE, DallArmi C, Voronov SV, McIntire LB, Zhang H, Moore AZ, Staniszewski A, Arancio O, Kim T-W, and Di Paolo G. Oligomeric amyloid ?-peptide disrupts phosphatidylinositol-4,5-bisphosphate metabolism Nature Neurosci. 2008 May; 11(5): 547-554. Landman N, Jeong SY, Shin SY, Voronov SV, Serban G, Kang MS, Park MK, Di Paolo G, Chung S, Kim TW. Presenilin mutations linked to familial Alzheimer’s disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism Proc Natl Acad Sci USA. 2006 Dec 19; 103(51): 19524-19529. Tech Ventures Reference: IR 2240 Licensing Contact: Jerry Kokoshka