Small molecule GAG binders for PET imaging of lysosomal storage and amyloid diseases
Proprietary Glycosaminoglycan-Interacting Small Molecules (GISMOs) that bind heparan sulfate with high affinity and stability. These compounds are being developed as PET imaging ligands for lysosomal storage diseases such as mucopolysaccharidoses and for amyloid diseases including Alzheimer's and Parkinson's.
Overview
Gismo Therapeutics is developing Glycosaminoglycan-Interacting Small Molecules (GISMOs), a class of low molecular weight compounds (under 500 Da) that bind directly to glycosaminoglycans (GAGs), particularly heparan sulfate. Because GAGs accumulate in the lysosomes of patients with lysosomal storage disorders and are also implicated in amyloid protein aggregation, GISMO-based PET ligands offer a novel imaging approach for diseases such as mucopolysaccharidoses (MPS), Alzheimer's disease, and Parkinson's disease. The platform is backed by multiple NIH SBIR grants and a filed patent application covering the core chemistry.
Technical specifications
- Direct GAG binding: GISMOs interact with heparan sulfate GAGs with high affinity and stable binding, confirmed by ELISA and biophysical methods.
- UV hypochromatic shift assay: Binding to GAGs produces a measurable hypochromatic effect in UV spectroscopy, enabling straightforward screening and analog characterization.
- Lead optimization program: A series of analogs has been generated around validated leads, with established structure-activity relationships identifying regions of the molecule amenable to derivatization.
- Favorable pharmacokinetics: Selected compounds have demonstrated acceptable half-life, bioavailability, and brain penetrance in preclinical pharmacokinetic studies.
- Safety profile: Acute toxicity studies in rodents have shown an acceptable tolerability profile for lead compounds.
- PET ligand derivatization: Functional groups can be appended to non-binding regions of the scaffold to create PET-compatible radioligands while retaining GAG affinity.
- Patentable novelty: Many compounds in the library, including planned PET derivatives, are novel and patentable.
Technology readiness level
The GISMO platform has been validated at the preclinical stage. Core binding activity has been confirmed through library screening and biophysical assays, and lead compounds have progressed through pharmacokinetic and acute toxicity evaluation in rodents. Analoging efforts are ongoing to identify scaffolds suitable for PET ligand derivatization, and binding assay methods are being refined to support further lead selection. In vivo evaluation of candidate PET ligands will require external collaboration, as the company is currently seeking partners with radiochemistry and imaging expertise to advance the program toward imaging studies in disease models.
About Gismo Therapeutics Inc.
Gismo Therapeutics Inc. is a biotechnology company focused on developing first-in-class, disease-modifying oral therapeutics for neurodegenerative conditions, specifically Alzheimer’s and Parkinson’s disease. The company was founded by Dr. Paul Gregor on the basis of its proprietary Glycosaminoglycan-Interacting Small Molecule (GISMO) technology. This platform targets fundamental biochemical processes involving heparan sulfate glycosaminoglycans (HS-GAGs), which are implicated in the internalization and aggregation of amyloid-beta and tau proteins, as well as alpha-synuclein, which drive the pathogenesis of amyloid diseases. By inhibiting these interactions, the company aims to reduce the propagation of aggregated proteins in the central nervous system.
The company serves as a developer of novel chemical entities intended to halt disease progression rather than simply manage symptoms. Their lead programs, such as GTC-3295 for Alzheimer’s disease, have demonstrated the ability to significantly decrease amyloid burden and hyperphosphorylated tau levels in preclinical transgenic mouse models. The company’s research has been supported by multiple grants from organizations including the National Institutes of Health (NIH) and the Michael J. Fox Foundation. Gismo Therapeutics actively pursues collaborative partnerships with academic institutions, such as the University of Kentucky and the Van Andel Research Institute, to advance its pipeline toward clinical trials and future therapeutic deployment.
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