Lewy Body Dementia (LBD)
Overview of Lewy Body Dementia (LBD)
Lewy body dementia (LBD) is a progressive neurodegenerative disorder defined by the accumulation of abnormal α-synuclein protein aggregates (Lewy bodies) within the cortical, limbic, and subcortical regions. Core clinical features encompass fluctuating cognition, visual hallucinations, REM sleep behavior disorder, and parkinsonian motor symptoms. It contains two subtypes, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). In DLB, the cognitive decline occurs either prior to or simultaneously with motor symptoms. In PDD, dementia develops following established motor symptoms.
Fig.1 Lewy body disorders (LBD): a spectrum with two endpoints. (Cersosimo M G., 2018)
Pathogenesis of Lewy Body Dementia (LBD)
The development of Lewy body dementia (LBD) is associated with the abnormal collection of alpha-synuclein protein into Lewy bodies and Lewy neurites, which spread similar to prions through linked neural networks. This results in the disruption of the synaptic functions, proteostasis, and the mitochondrial systems which, in turn, leads to the degeneration of the cholinergic and dopaminergic systems. Genetic risks such as GBA mutations, in the presence of Alzheimer's co-pathology, are known to amplify neurotoxicity and speed up the progress of the disease.
Fig.2 Across the disease timeline of Lewy body dementia (LBD). (Loveland P M, et al., 2023)
Therapeutic Development for Lewy Body Dementia (LBD)
| Drug Name | Mechanism of Action | Targets | NCT Number | Research Phase |
| LY3154207 | Potent and selective positive allosteric modulator of dopamine D1 receptors. Enhances D1 receptor-mediated signaling without inducing overstimulation. | Dopamine D1 receptor | NCT03305809 | Phase II |
| Nelotanserin | Inverse agonist of serotonin 5-HT2A receptors. Reduces hallucinations and improves sleep architecture by modulating serotonergic signaling. | 5-HT2A receptor | NCT02640729 | Phase II |
| AR1005 | Phosphodiesterase type 5 (PDE5) inhibitor. Increases cyclic guanosine monophosphate (cGMP) levels to enhance neuroplasticity and cerebral blood flow. | Phosphodiesterase 5 (PDE5) | NCT06537076 | Phase IIa |
| RVT-101 | Selective serotonin 5-HT6 receptor antagonist. Modulates neurotransmitter release (e.g., acetylcholine, glutamate) to improve cognitive function. | 5-HT6 receptor | NCT02669433 | Phase IIb |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen focuses on offering advanced diagnostic and therapeutic development services for rare neurodegenerative diseases like Lewy body dementia (LBD). Our team concentrates on developing sophisticated disease models for better understanding of pathogenesis of LBD. Moreover, we employ innovative blood-brain barrier (BBB) models to improve the delivery and efficacy of therapeutic compounds.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- MPTP Induced Model
- 6-hydroxydopamine Induced Model
- SNCA Overexpression Model
- PINK1 Knockout Model
- LRRK2 G2019S Model
- Other Models
At Protheragen, we are dedicated to supporting the development of innovative therapies through comprehensive preclinical research services. Our expertise spans pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies, ensuring a thorough evaluation of your therapeutic candidates. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Cersosimo M G. Propagation of alpha-synuclein pathology from the olfactory bulb: possible role in the pathogenesis of dementia with Lewy bodies[J]. Cell and tissue research, 2018, 373(1): 233-243.
- Loveland P M, Yu J J, Churilov L, et al. Investigation of inflammation in Lewy body dementia: a systematic scoping review[J]. International Journal of Molecular Sciences, 2023, 24(15): 12116.