Gain Therapeutics' SEE-Tx™ Platform Shows Increasing Evidence in Treating Diseases Caused by Protein Misfolding

Image by National Cancer Institute on Unsplash

The following post was written and/or published as a collaboration between Benzinga’s in-house sponsored content team and a financial partner of Benzinga.

Medical and technological advancements are extending our lifespan. Unfortunately, as human life expectancy rises, so does the risk of people developing a degenerative disease such as Alzheimer's, Parkinson's, or diabetes.

These diseases are not caused by bacteria or viruses but by genetic mutations which in certain mutations, results in misfolded proteins.

Basic biology teaches that proteins are vital because they engage in almost every activity within the cell. If damaged, the result can be dangerous. Over time, mutations and thermodynamics (and some other external factors) work against the body. The problem faced by pharmaceutical companies is that about 90% of disease-causing proteins cannot be targeted by current therapies due to the lack of a known addressable binding site.

The problem with misfolded proteins is that when they are misfolded they cannot properly traffic through the cell and cause a build-up of toxic substrate. Gain’s technology is able to solve this problem by finding binding sites on proteins that were previously thought to be undruggable.

Gain's discovery platform SEE-Tx™ can find novel allosteric binding sites that when bound to by a small molecule (Gain's STAR compounds), misfolded proteins are returned to their correct conformation.

Catalan Institution for Research and Advanced Studies (ICREA) research professor and Chief Scientific Officer of Gain Therapeutics Inc. GANX, Xavier Barril, Ph.D., invented the technology in the Barril Lab at the University of Barcelona. Gain is a spinoff of Barril’s other company, Minoryx Therapeutics, and is one of the few companies that can expedite the identification, validation, and design of novel drug compounds to target regulatory allosteric sites on enzymes.

What Is SEE-Tx™?

SEE-Tx™, or Site-Directed Enzyme Enhancement Therapy platform, is a computational platform that rapidly finds previously unidentified allosteric binding sites. It predicts the druggability of the binding site by filtering through multimillion-compound libraries in a fraction of the time the current laborious phenotypic cell-based screenings are capable of. 

The image shows actual SEE-Tx results for a protein. The pink molecule is in the binding site and the green and salmon-colored meshes represent different binding hotspots. 

Gain optimizes the pool of small molecules that may bind to the druggable hot spots and can identify and develop proprietary structurally targeted allosteric regulators (STARs) — selected compounds that stabilize misfolded proteins and restore biological activity - ‘gain of function’. 

STARs offer a variety of advantages over traditional therapies — streamlined oral dosing, improved delivery to dense tissues (bone and cartilage), ability to cross the blood-brain barrier (BBB), and synergy with current gene therapy and enzyme replacement therapy (ERT) approaches.

In numbers, Gain revealed that the SEE-Tx™ platform is able to:

• Identify allosteric sites on target enzymes in 5 to 6 weeks
• Screen compounds for activity in 2 to 3 weeks
• Validate the compounds in as little as 2 to 3 months

Promising Results

Recently, Gain announced the positive effects of its 2 lead STAR candidates for the treatment of Gaucher and GBA1 Parkinson's Disease in a study conducted at the University of Maryland School of Medicine.

To test the efficacy of the candidates developed by Gain, the study used human induced pluripotent stem cells (iPSC) derived from patients with GD- and GBA-associated Parkinson’s Disease. The study revealed that the compounds increase the levels of GCase protein, its transport to the lysosome, and its enzymatic activity. In dopaminergic neurons, the 2 lead STAR chaperones also decrease the levels of α-synuclein-p129.

The promising results demonstrated the potential of the 2 candidates to treat GBA1-associated Parkinson’s Disease and were a testimony to the capabilities of Gain’s proprietary platform. Comprehensive study results will be presented at the Michael J. Fox Foundation’s upcoming  Innovating from Drug Discovery to the Clinic: Novel Approaches to PD Therapeutic Development to be held on November 10, 2021. 

The company anticipates initiating IND-enabling studies for Gaucher and Parkinson’s disease in the 4th quarter of 2021. 

To learn more about Gain Therapeutics visit its website here.

The preceding post was written and/or published as a collaboration between Benzinga’s in-house sponsored content team and a financial partner of Benzinga. Although the piece is not and should not be construed as editorial content, the sponsored content team works to ensure that any and all information contained within is true and accurate to the best of their knowledge and research. This content is for informational purposes only and not intended to be investing advice.