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. Many of these dying neurons produce dopamine, an important chemical (a neurotransmitter) 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 substantia nigra decreases, leaving the affected patient 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 α-synuclein. This protein is found widely in the brain and 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 caused by the deposition of α-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.
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.
In May 2022, Asceneuron has initiated a preclinical proof-of-concept study to assess the disease-modifying properties of Asceneuron’s OGA inhibitor ASN51 in a preclinical model of inherited PD. The genetic model is characterized by the overexpression of α-synuclein harbouring the A53T mutation known to cause early-onset, familial PD in humans. Aggregated forms of α-synuclein are the main component of the characteristic Lewy body pathology and thus thought to be causative of the loss of dopaminergic neurons in PD. The aim of this study is to extend previously published findings demonstrating a reduction of motor impairment with Asceneuron’s OGA inhibitors (e.g., Permanne et al., ACS Chem. Neurosci. 2022) to this alternative genetic disease model.
Patient associations
1-15% of dementia cases
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
2015 818 billion USD
2030 > 2000 billion USD
85+ 37%
75<>84 44%
65<>74 15%
<65 4%
(US, 2016)