Fortis: A New Rapid Screening Assay for Cognitive Enhancement Compounds

Introduction

Synaptic plasticity which is defined as Activity-dependent synaptic changes, is a critical factor in multiple forms of cognitive function, such as learning and memory. Cognitive impairment (CI) is highly prevalent worldwide but despite the severity of this problem, there is still no appropriate solution available. It is believed that targeted manipulation of mechanisms leading to an increase in synaptic plasticity may potentially improving cognitive function under pathological, or even physiological, conditions. AMPA receptors are widely studied as targets to increase synaptic plasticity. The central role of AMPA receptors in memory and learning emphasize the need of novel screening methods to identify potentiates.

The Technology

Based on the strong link between AMPA receptors’ synaptic function and cognitive performance, we have developed a new screening assay to detect molecules capable of modulating synaptic plasticity by increasing synaptic AMPA receptor presence, using a regular 96-well plate reader. The hit compounds yielded by this assay should represent strong candidates as future cognitive enhancers. The proposed screening method is flexible, fast, cost-effective, and it is expected to yield high-content lead compounds with strong prospects of clinical success (figure 1).

Advantages

• While traditional approach is based on Mechanism-related therapies, using Fortis, disease mechanism is irrelevant.
• Fortis doesn’t require specific expertise or specialized equipment.
• FORTIS technology uses a fast HTS scoring, in comparison to traditional methods based on time-consuming pharmacological testing.

Patent Status

PCT application was filed on November 20th , under the application number PCT/IL2020/051309

Partnership

FORTIS is a novel screening assay for new compounds exhibiting synaptic enhancement capabilities. We offer our method and expertise for co-development with research institutes or companies which have automation and screening library capabilities, as well as proprietary small molecules library in order to explore and develop new compounds. Joint IP will be issued to the new molecules.

Principal Investigator

Dr. Shira Knafo, NIBN and the Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Israel.