Protein Misfolding
Protein misfolding is the root of many diseases, including lysosomal storage disorders and neurodegenerative diseases.
Since the precise 3D structure of a protein is essential for its function, misfolding can result in significant downstream consequences. If this misfolding occurs to an enzyme, oftentimes the catalytic reaction can no longer take place, leading to substrate accumulation to toxic levels and subsequent cellular dysfunction.
There are many reasons why enzymes misfold. The most obvious is a genetic mutation in which a change to the amino acid sequence leads to an incorrect folding pattern. However, there are other causes of misfolding that can affect even wildtype enzymes, including states that increase cellular stress such as aging and inflammation.
Gain believes that if we can guide the misfolded enzymes, mutant or wildtype, back into their functional 3D shape, we can reignite the catalytic reactions and eliminate the toxic substrate buildup that causes many diseases.
SEE-Tx™ Platform
Gain is utilizing its Site-Directed Enzyme Enhancement Therapy (SEE-Tx™) platform to guide misfolded enzymes back into their proper shape in order to treat a range of diseases.
SEE-Tx™ is a computational platform that uses the published 3D structure of enzymes and a proprietary computational technology to discover new allosteric binding sites and predict their druggability. The output from the SEE-Tx™ platform are newly discovered binding sites that for the first time, can be targeted for therapeutic benefit to correct enzyme misfolding, thus restoring function and eliminating the subsequent toxic substrate buildup that causes disease.
DIFFERENTIATED and PATENTED Highly-specific, efficient and cost-effective drug discovery approach
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STARs
Following site identification through the SEE-Tx™ platform, Gain uses proprietary structure-based computational methods to scan a library of small molecule compounds to fit the target site.
This method results in efficient and inexpensive candidate compound identification, after which Gain conducts medium-throughput assays to Identify novel, final lead program candidates, termed Structurally Targeted Allosteric Regulators (STARs). Importantly, STARs do not interact with the enzymes’ active sites, enhancing both safety and efficacy.
Given that STARs are small molecule therapies, they have several significant advantages over the current standard of care for disorders associated with protein misfolding, including enzyme replacement therapy and gene therapy.
Simple Oral Pill
They can be administered as a simple oral pill
Biodistribution
They can reach organs and tissues that are not accessible through current therapeutic options, including the brain, bone and cartilage
Cost-effective
They are easy and cost-effective to manufacture
As a result of its approach, Gain is one of very few companies that can expedite the identification, validation and design of novel drug compounds to target regulatory allosteric sites on enzymes.