Asceneuron aims to address learning and memory deficits in Parkinson’s disease dementia and Lewy body dementia

What are Parkinson’s disease dementia and Lewy Body dementia?

Parkinson’s disease (PD) is a progressive, degenerative neurological movement disorder that affects approximately 7 million people worldwide. It is the second most common neurodegenerative disorder after Alzheimer's disease.

Up to 80% of Parkinson’s disease patients will develop Parkinson’s disease dementia (PDD) that is characterized by a progressive loss of memory and decline in intellectual abilities.

About 15% of Parkinson’s disease diagnoses include so-called Parkinson’s plus syndromes. One of these syndromes is Lewy body dementia (LBD), also known as dementia with Lewy bodies (DLB), a form of progressive dementia accounting for 20% of dementias in people over the age of 65.


What are the symptoms of these diseases?

The main symptoms of Parkinson's disease involve motor control, such as tremor (hands, arms, legs, jaw and face), slowness of movement, stiffness of the limbs and trunk as well as postural instability. Many patients develop a decline in thinking and reasoning known as Parkinson’s disease dementia if it occurs more than one year after the initial diagnosis of Parkinson’s disease. Common symptoms for PDD include decline in memory, concentration and judgment, visual hallucinations, depression, irritability and anxiety.

The central feature of Lewy body dementia (LBD) is progressive cognitive decline, combined with pronounced fluctuations in alertness and attention, complex visual hallucinations and motor symptoms such as rigidity and the loss of spontaneous movement. It can easily be mistaken for Alzheimer’s disease (AD) or for Parkinson’s disease dementia (PDD).


Understanding Parkinson’s disease, PDD and LBD

Parkinson’s disease

Parkinson’s disease initially affects neurons in an area of the brain called substantia nigra. Some of these dying neurons produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. As the disease progresses, the amount of dopamine produced in the brain decreases, leaving a person unable to control movement normally.

As Parkinson's disease progresses, it affects also other brain areas and nerve cells important for mental functions, including memory and the ability to pay attention, make sound judgments and plan the steps needed to complete a task.

Parkinson's disease dementia and dementia with Lewy bodies

The key pathological hallmark found in brains of Parkinson's disease and Parkinson's disease dementia patients are abnormal microscopic deposits composed of alpha-synuclein. This protein is found widely in the brain but its normal function is not yet well understood. The deposits are called "Lewy bodies". Lewy bodies are also found in several other neurodegenerative brain disorders, including dementia with Lewy bodies (LBD). Evidence suggests that Parkinson's disease and Parkinson's disease dementia, and dementia with Lewy bodies, may be linked to the same underlying abnormalities in brain processing of alpha-synuclein.


Asceneuron’s innovation in PDD and DLB

Several symptomatic treatments addressing motoric disturbances in PD are currently available. In contrast, there is a very high unmet medical need for novel symptomatic medications to mitigate the cognitive decline in Parkinson’s disease dementia patients, since available options have limited efficacy and considerable side effects. As the disease progresses, balancing the benefits of medications with their side effects becomes challenging for caregivers.

Asceneuron has generated small molecules of novel chemical classes that have the potential to deliver novel, well-tolerated and efficacious drugs to treat learning and memory deficits in dementia. Our positive allosteric modulators of the M1 muscarinic acetylcholine receptor have the potential to bring the first approved treatment for PDD to patients and a new class of molecules for the treatment of dementia in general. M1 PAMs induce a change in the shape of the receptor, enhancing binding to the neurotransmitter acetylcholine. As a result, receptor activity is potentiated so that it can still fulfill its signaling functions, critical for cognition, even in situations where acetylcholine levels are reduced as observed in Parkinson’s disease dementia and other dementia in general.

Given the high unmet medical need in PDD, a symptomatic treatment for one of the more debilitating facets of PD would bring significant benefit to PD patients and their caregivers.


Patient associations

Parkinson's key facts
ABOUT LEWY BODY DEMENTIA

1-15% of dementia cases


 

ABOUT PARKINSONISM

Umbrella term given to a group of conditions that feature Parkinson’s-type symptoms.

85% : Parkinson’s disease

15% : other rare conditions such as LBD or PSP


 

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)