Huntington disease

Aggregation inhibitors

APG has identified a new way of reducing aggregation. 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 a lead candidate with excellent in vitro blood brain barrier penetrability and ADMET properties.

 

Current status of the drug discovery program

We are optimizing our lead compound.


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.

Mutated huntingtin 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.