Asceneuron targets the root cause of neurodegeneration in rare neurodegenerative diseases such as Progressive Supranuclear Palsy

What is Progressive Supranuclear Palsy (PSP)?

Progressive Supranuclear Palsy, also known as Steele-Richardson-Olzewski syndrome, is a rapidly progressing neurodegenerative disorder.

PSP is often misdiagnosed because it is relatively rare and certain symptoms are similar to Parkinson’s disease. However, PSP is much more common than previously believed. Its prevalence is about 5-7 per 100,000 individuals. Symptoms generally appear in the 60s-70s, but can affect people from the age of 40 onwards.

There is currently no treatment available to cure this disease.


What are PSP symptoms?

PSP affects nerve cells in parts of the brain which are important for the control of certain movements. The first symptoms are frequent and unexpected backward falls, and blurring of vision. As the disease progresses, PSP is also characterized by eye movement problems (impaired ability to move the eye up or down, involuntary closure of eyelids). The impaired ability to move the eyes in the vertical direction is clinically described as vertical gaze palsy. People with PSP also show difficulties in speaking and swallowing, behavioural changes, impairment of bowel and bladder functions. As the disease progressively evolves, patients tend to become disabled within a few years.


Understanding PSP

The hallmark of PSP is the accumulation of abnormal deposits of the protein tau in nerve cells in the brain, so that the cells do not function properly and eventually die. The appearance of deposits of the microtubule-associated tau protein termed ‘neurofibrillary tangles’ is a common feature of tauopathies that is shared with Alzheimer’s disease. These neuronal tau deposits are known to be a major driver of neurodegeneration.

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Appearance of neurofibrillary tangles (right) in a preclinical model compared to a healthy reference (left)


Asceneuron’s innovation for PSP

Currently there is no effective treatment for PSP. Given the situation of high unmet patient need, neurologists use a variety of medications off-label. While these medications are directed against specific symptoms of PSP, none of them can halt disease progression.

Based upon the knowledge that the formation of neurofibrillary tangles drives the disease, we have designed molecules which prevent the formation of these toxic tau aggregates in the brain. As such we are targeting the root cause of neurodegeneration. The underlying molecular mechanism is the inhibition of an enzyme that removes the sugar modification N-acetylglucosamine from tau and is termed O-GlcNAcase. As a result of O‑GlcNAcase inhibition, tau bears more of the sugar which blocks its aggregation into toxic assemblies.

Our first drug candidate for PSP has entered human clinical testing in healthy volunteers.


Patient associations

PSP
ABOUT PSP

1% of dementia cases


DEMENTIA WORLWIDE

2015      46.8 Million

2030      74.7 Million

2050     131.5 Million


GLOBAL COST OF DEMENTIA

2015          818 billion USD

2030     > 2000 billion USD


AGE OF PATIENTS

85+              37%

75<>84        44%     

65<>74        15%

<65                4%    

(US, 2016)