PDE5 inhibitor for Alzheimer's treatment

This technology is a PDE5 inhibitor that can be used for the treatment of Alzheimer’s Disease.

Unmet Need: PDE5 inhibitor for restoring memory and reducing amyloid buildup in Alzheimer’s

Despite decades of research, current Alzheimer’s treatments do not reverse cognitive decline or repair the damage to neural circuits underlying memory loss. The current standard of care also fails to adequately reduce beta-amyloid accumulation or improve synaptic resilience. Addressing these shortcomings is essential for slowing the progression and enabling functional recovery in patients.

The Technology: Treatment to target memory loss and amyloid accumulation in Alzheimer’s Disease

This technology is a dual-synthesized PDE5 inhibitor formulated to increase intracellular cGMP levels in neurons, thereby enhancing signaling pathways involved in synaptic plasticity and memory. By inhibiting PDE5 and blocking the breakdown of cGMP, the compound can enhance the activity of proteins related to memory. This compound can penetrate the blood-brain barrier, thereby accessing the central nervous system and leading to reduced amyloid accumulation.

This technology has been validated within Alzheimer’s mouse models.

Applications:

• Drug to decrease amyloid plaque accumulation
• Therapeutic for the treatment of Alzheimer’s Disease
• Treatment for erectile dysfunction and hypertension
• Research tool for investigating PDE5 and cGMP signaling pathways
• Method for modulating secretase protein activity
• Platform for screening phosphodiesterase inhibitors

Advantages:

• Dual functional benefits
• Improves brain penetration
• Enhances the pharmacokinetics of widely used PDE5 inhibitors

Lead Inventor:

Donald W. Landry, M.D., Ph.D.

Patent Information:

Patent Issued (US 9,974,782)

Related Publications:

• Zuccarello E, Acquarone E, Calcagno E, Argyrousi EK, Deng SX, Landry DW, Arancio O, Fiorito J. “Development of novel phosphodiesterase 5 inhibitors for the therapy of Alzheimer’s disease.” Biochemical pharmacology. 2020 Jun 1;176:113818.

• Zuccarello E, Zhang H, Acquarone E, Pham D, Staniszewski A, Deng SX, Landry DW, Arancio O, Fiorito J. “Optimizing metabolic stability of phosphodiesterase 5 inhibitors: Discovery of a potent N-(pyridin-3-ylmethyl) quinoline derivative targeting synaptic plasticity.” Bioorganic & medicinal chemistry letters. 2023 Aug 15;92:129409.

Tech Ventures Reference:

• IR CU12089, 2329, 2883

• Licensing Contact: Jerry Kokoshka