Alzheimer's disease

What is Alzheimer’s disease?

Alzheimer’s disease is a slowly progressing and irreversible disease causing the degeneration of nerve cells in parts of the brain which are important for cognition and memory. It the most common cause of dementia, a general term for loss of memory and other mental abilities severe enough to interfere with daily life. Dementia is estimated to currently affect more than 48 million people worldwide.

Age is the largest risk factor for Alzheimer’s disease and to date, no available treatments are able to slow down or stop the progression of the disease. Due to increasing life expectancy, Alzheimer’s disease is viewed as one of the largest healthcare problems of this century, imposing a major economic burden on societies in the Western and developing world.
 

What are the symptoms of Alzheimer’s disease?

Early symptoms of Alzheimer’s disease include short-term memory loss, as well as mood and behavior changes. As the disease progresses, Alzheimer’s patients gradually lose cognitive function (memory, language, orientation) and require assistance in performing daily activities. At an advanced stage, they need constant assistance due to more serious memory loss and difficulties with speaking, walking and swallowing.
 

Understanding Alzheimer’s disease

Alzheimer’s disease causes the degeneration of nerve cells in large parts of the brain. The main hallmarks of Alzheimer’s disease are:

• Progressive accumulation of amyloid-β (Aβ) peptides in neuritic / senile plaques outside neurons in the brain parenchyma, interfering with the neuron-to-neuron communication at synapses and possibly contributing to cell death.

• Aβ peptides also accumulate as vascular amyloid around the blood vessels of the brain which is seen as cerebral amyloid angiopathy (CAA). Vascular amyloid causes vascular dysfunction in the brain and i.e., interferes with the uptake of essential nutrients from the blood into the brain.

• Abnormal deposits of the microtubule-associated protein tau in the form of neurofibrillary tangles inside neurons, blocking the transport of cargo inside neurons. This is a major driver of neuronal dysfunction and cell death, and closely linked to clinical disease progression. Eventually, both extracellular amyloid-β deposits and intracellular tau tangles cause irreversible damage in the brain, leading to atrophy of the brain and a loss of cognitive function. Eventually, both amyloid deposits and tangles cause irreversible damage in the brain, leading to atrophy of the brain and a loss of cognitive function.

Comparison of a healthy brain (left) and a brain affected by Alzheimer’s (right):
Plaques and tangles lead to shrinkage of the brain and neuroinflammation
 

Asceneuron’s innovation in Alzheimer’s disease

Current Alzheimer’s treatment options can help extend the autonomy of Alzheimer’s patients and reduce their motor symptoms. However, none of them are able to slow down or stop the progression of the disease.

Based on the knowledge that the formation of neurofibrillary tangles drives the progression of Alzheimer’s 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 the glycoside hydrolase enzyme OGA that removes the sugar N-acetyl-glucosamine (GlcNAc) from tau. As a result of OGA inhibition, tau bears more of this specific sugar moiety which blocks its aggregation into toxic assemblies.

Our next-generation OGA inhibitor ASN51 is a drug candidate for AD has completed human clinical testing in healthy volunteers ASN51 was awarded USD 2.2 million from the Alzheimer’s Drug Discovery Foundation for a first in human Phase I study. Another biomarker-centric clinical trial with ASN51 currently recruits Alzheimer's disease patients.

Patient associations

• Alzheimer's Association
• Alzheimer Europe
• Deutsche Alzheimer Gesellschaft Selbsthilfe Demenz
• Association France Alzheimer
• Alzheimer's Society