APG has identified a new way of preventing aggregation, oligomer formation and seeding of mutated huntingtin. The drug candidate is a small molecule, which may be applied orally. Clinically modifying the function of the identified drug target has the potential to modulate HD pathology, improve symptoms, and slow down cognitive decline, behavioral changes and movement abnormalities. We are currently testing analogs of our hits with a binding assay to identify small molecules with improved affinity to the drug target. We have so far early leads with excellent in vitro blood brain barrier penetrability and high solubility.
The lead has low molecular weight and good blood brain barrier solubility in vitro.
Current status of the drug discovery program
Our lead compound is tested in pharmacokinetic mice studies. Until mid 2018 we will finish a proof-of-concept Huntington's disease mouse model study.
Mutated huntingtin form intraneuronal inclusions are located in the striatum, cerebral cortex, cerebellum, and the spinal cord. The inclusion bodies are a pathological hallmark of HD. Inclusion bodies are found in neurons before the manifestation of behavioral symptoms and significant neuronal death.
There are no disease modifying therapies for HD available! In Europe and North America there are 90,000 patients who suffer from HD. It is estimated that there are 600,000 gene carriers who will inescapably develop symptoms over time.