Huntington disease

Aggregation inhibitors

APG has identified a new way of preventing aggregation 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.

 

Their Properties

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. 


Background of Huntington's Disease

Huntington's disease (HD) is a fatal, progressive neuro-degenerative disorder that can be inherited from one generation to another as an autosomal dominant trait. As the disease progresses, patients show choreatic movements, speech impairment, cognitive impairment, anxiety, and difficulty in swallowing. After first symptom manifestation, patients die within 10 – 20 years.

Aggregation of mutated protein

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. 

Rare disease with unmet medical need

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.