Primary Lateral Sclerosis (PLS)
Primary lateral sclerosis, or PLS, is an uncommon form of a neurodegenerative disease which impacts the upper motor neurons. In order to tackle the challenges associated with PLS, Protheragen has dedicated advanced technologies and specialized personnel concentrated on developing new treatment options. We offer holistic aid that will reduce your journey from developing a drug candidate to commercializing it.
Introduction to Primary Lateral Sclerosis (PLS)
Primary lateral sclerosis (PLS) is a rare, non-familial neurodegenerative disorder characterized by the progressive degeneration of upper motor neurons (UMNs) in the corticospinal and corticobulbar tracts. As opposed to amyotrophic lateral sclerosis (ALS), PLS tends to spare lower motor neurons (LMNs), which leads to slower disease progression and better overall prognosis. The disease presents with painless spasticity, hyperreflexia, and progressive weakness of the limbs, bulbar musculature, and later respiratory muscles.
Fig.1 Current diagnostic criteria for primary lateral sclerosis (PLS). (Vacchiano V, et al., 2024)
Pathogenesis of Primary Lateral Sclerosis (PLS)
The development of primary lateral sclerosis (PLS) centers upon the progressive neurodegeneration of upper motor neurons due to glutamate-driven excitotoxicity, oxidative damage, and failure in cytoskeletal mechanisms. Overactivity of AMPA/kainate receptors results in calcium overload and neuronal apoptosis, especially Betz cells in the motor cortex. Oxidative damage is worsened by mitochondrial dysfunction and the accumulation of free radicals, and disruption of axonal transport coupled with the aggregation of neurofilaments compromises neuronal integrity.
Fig.2 Primary lateral sclerosis (PLS) and progressive muscular atrophy (PMA) patients displayed similar cognitive and behavioral impairment profile than amyotrophic lateral sclerosis (ALS) patients. (José Manuel Matamala., 2019)
Therapeutic Development for Primary Lateral Sclerosis (PLS)
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Dalfampridine | Potassium channel blocker that improves action potential conduction in demyelinated axons. | Voltage-gated potassium channels | Phase II/III |
| Carbidopa-levodopa | Levodopa (dopamine precursor) crosses the BBB and is converted to dopamine; carbidopa prevents peripheral breakdown. | Aromatic L-amino acid decarboxylase, dopamine receptors | Phase I |
| Levetiracetam | Modulates synaptic neurotransmitter release by binding to synaptic vesicle protein SV2A. | Synaptic vesicle glycoprotein 2A (SV2A) | Phase I |
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
At Protheragen, we are a preclinical research service provider and offers one-stop primary lateral sclerosis (PLS) diagnostic and therapeutic development solutions. We employ state-of-the-art disease models for biomarker discovery, target validation, drug applicability assessments, and mechanism studies. Our chief objective remains to close the divide between scientific investigation and practical clinical use.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
- ALS2 knockout models completely eliminate the ALS2 gene, which encodes the alsin protein involved in neuronal maintenance and trafficking.
- Conditional ALS2 knock-in models introduce tissue-specific mutations to study selective UMN degeneration.
Protheragen also provides advanced blood-brain barrier (BBB) model development services, including 2D and 3D models, to enhance CNS drug delivery testing and neuroprotective agent validation. Using these models, we can explore the mechanisms of primary lateral sclerosis (PLS) and conduct pharmacodynamic (PD), pharmacokinetic (PK), and toxicology studies of candidate therapeutics. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Vacchiano V, Bonan L, Liguori R, et al. Primary lateral sclerosis: an overview[J]. Journal of Clinical Medicine, 2024, 13(2): 578.
- José Manuel Matamala. Primary lateral sclerosis and progressive muscular atrophy as a multidomain brain disorder[J]. Journal of Neurology, Neurosurgery & Psychiatry, 2019.