Upper Motor Neuron Diseases (UMND)
Rare upper motor neuron diseases (UMND) encompass a cluster of neurodegenerative diseases impacting the motor circuits in the central nervous system (CNS). Protheragen has deep knowhow in UMND pretty well due to the broad skills of researchers and scientists in the company. Commitment to developing innovative therapies for UMND with unmet therapeutic requirements is our passion.
Introduction to Upper Motor Neuron Diseases (UMND)
Upper motor neuron diseases (UMND) refer to a spectrum of neurodegenerative diseases which involves progressive loss of upper motor neurons (UMNs) in the motor cortex, brainstem, and spinal cord. Accompanying the progression of this disease are disabling symptoms – spasticity, hyperreflexia, muscular atrophy, and voluntary motor activity suppression. There are two types of UMNDs, hereditary and acquired, with prominent examples being primary lateral sclerosis (PLS), hereditary spastic paraplegia (HSP), and some variants of amyotrophic lateral sclerosis (ALS).
Fig.1 Characteristics of three classic upper motor neuron diseases (UMND). (Fullam T, Statland J., 2021)Pathogenesis of Upper Motor Neuron Diseases (UMND)
Genetic alterations, improper protein folding, glutamate-associated excitotoxicity, mitochondrial damage, neuroinflammation from glial cell activation, disrupted axonal transport, and inflammation too driven by glial activation all contribute to the pathogenesis of upper motor neuron diseases (UMND). Together, these processes invoke oxidative stress, skew intracellular trafficking, and sustain inflammatory damage which leads to chronic inflammation, and thus, demanding treatment approaches.
Fig.2 Schematic diagram of the motor nervous system. (Zuccaro E, et al., 2021)
Therapeutic Development for Upper Motor Neuron Diseases (UMND)
The current approaches to treat upper motor neuron diseases (UMND) concentrate mainly on symptom relief, including intrathecal baclofen (ITB) or dopaminergic modulation for spasm alleviation, while actual disease modifying therapies remain sparse. Some of the challenges include heterogeneous genetic origins, absence of definitive biomarkers, along with the inability to selectively target the upper motor neurons which are more susceptible to damage. Some of the therapeutic pipelines are displayed in the table below.
| Drug Names | Targets | Indications | NCT Number | Research Phase |
| Carbidopa-levodopa | Striatal dopamine receptors | Primary lateral sclerosis (PLS), amyotrophic lateral sclerosis (ALS) | NCT03929068 | Phase II |
| Apomorphine | Dopamine receptors, serotonin receptors | Corticobasal syndrome | NCT04786158 | Phase II |
| Intrathecal baclofen (ITB) | GABA-B receptors | Hereditary spastic paraplegia (HSP) | NCT06844734 | Phase II/III |
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
As a specialized preclinical research service provider, Protheragen is committed to accelerating breakthroughs in rare upper motor neuron diseases (UMND). Our end-to-end solutions span diagnostic development, novel therapeutic development, precision disease modeling, and rigorous preclinical validation. By leveraging cutting-edge technologies and validated models, we bridge the gap between research innovation and clinical translation, empowering partners to advance promising therapies from concept to commercialization.
Types of Rare Upper Motor Neuron Diseases (UMND)
| A-N | |
| Bilateral Striatal Necrosis Corticobasal Syndrome Dystonia Familial Spastic Paraparesis Hereditary Spastic Ataxia |
Hereditary Spastic Diplegia Hereditary Spastic Paraplegia Hereditary Spastic Tetraplegia Konzo Neurolathyrism |
| O-Z | |
| Primary Lateral Sclerosis (PLS) Primary Progressive Aphasia Primary Progressive Cerebellar Ataxia Primary Progressive Multiple Sclerosis |
Primary Progressive Paralysis Progressive Hemifacial Atrophy Progressive Supranuclear Palsy Pseudobulbar Palsy |
Therapeutic Development Services
By Mechanism of Action
- Neuroprotective Agent Development
- Glutamate Modulator Development
- Anti-neuroinflammatory Drug Development
- Antioxidant Development
- Mitochondria-targeted Drug Development
- Protein Misfolding Inhibitor Development
- Protein Aggregation Inhibitor Development
- Excitotoxicity Inhibitor Development
- Muscle Relaxant Development
- More
Disease Model Development Services
In Vitro Model Development
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 rare upper motor neuron diseases 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
- Fullam T, Statland J. Upper motor neuron disorders: primary lateral sclerosis, upper motor neuron dominant amyotrophic lateral sclerosis, and hereditary spastic paraplegia[J]. Brain Sciences, 2021, 11(5): 611.
- Zuccaro E, Piol D, Basso M, et al. Motor neuron diseases and neuroprotective peptides: A closer look to neurons[J]. Frontiers in Aging Neuroscience, 2021, 13: 723871.