Mixed Motor Neuron Diseases
Mixed motor neuron diseases cause the simultaneous degeneration of upper and lower motor neurons, a dual impact that weakens nearly every aspect of voluntary movement. Researchers at Protheragen are applying those early insights in the lab to build next-generation therapies that promise to expand the treatment toolkit for someone living with a mixed motor neuron illness.
Overview of Mixed Motor Neuron Diseases
Mixed motor-neuron diseases form a clinically and genetically diverse set of neurodegenerative conditions in which both upper motor neurons in the cerebral cortex and lower motor neurons within the brainstem and spinal cord degenerate simultaneously. Patients frequently exhibit the tell-tale spasticity and brisk reflexes of upper-neuron damage alongside the weakness, wasting, and diminished reflexes that signal lower-neuron involvement.
Fig.1 Status of the most advanced gene therapies for motor neuron diseases (MNDs) and muscular dystrophies. (Chamakioti M, et al., 2022)
Pathogenesis of Mixed Motor Neuron Diseases
Mixed motor neuron disorders arise from a complex fusion of hereditary mutations and fundamental cellular failure. Altered versions of proteins such as TDP-43 and SOD1 pile into clumps that poison neighbouring tissue, while overactive glial cells fan the flames of chronic inflammation. Lesions ultimately strike both upper and lower neurone pools, propelling disturbances through at least three major conduits: impaired RNA processing, mitochondrial energy collapse, and a stall in axonal transport machinery.
Fig.2 Genes implicated in various motor neuron diseases (MNDs). (Antonakoudis A, et al., 2025)
Therapeutic Development for Mixed Motor Neuron Diseases
| Drug Name | Indications | Mechanism of Action | NCT Number | Research Phase |
| Dazucorilant | Amyotrophic lateral sclerosis (ALS) | Selective glucocorticoid receptor modulator (GRM) reducing neuroinflammation and muscle wasting | NCT05407324 | Phase II |
| Tofacitinib | Amyotrophic lateral sclerosis (ALS) | JAK-STAT pathway inhibitor suppressing neuroinflammation and microglial activation | NCT06689982 | Phase I |
| 3K3A-APC | Amyotrophic lateral sclerosis (ALS) | Modified activated protein C (APC) with cytoprotective and anti-inflammatory effects | NCT05039268 | Phase II |
| Dalfampridine | Hereditary spastic paraplegia with motor neuropathy | Potassium channel blocker improving axonal conduction and motor function | NCT05613114 | 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
Specializing in comprehensive solutions for mixed motor neuron diseases, Protheragen integrates diagnostic development with cutting-edge in vitro diagnostic (IVD) kits for early disease identification. Our therapeutic development pipeline leverages exclusive disease models, such as physiologically representative blood-brain barrier (BBB) models, to expedite the exploration and authentication of central nervous system (CNS) targeted treatments.
Types of Mixed Motor Neuron Diseases
Amyotrophic Lateral Sclerosis (ALS)
Progressive Bulbar Palsy (PBP)
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
At Protheragen, we are committed to validating and optimizing therapies for mixed motor neuron diseases through preclinical studies including pharmacodynamics (PD), pharmacokinetics (PK) and toxicology to ensure their successful regulatory approval. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Chamakioti M, Karantzelis N, Taraviras S. Advanced gene-targeting therapies for motor neuron diseases and muscular dystrophies[J]. International Journal of Molecular Sciences, 2022, 23(9): 4824.
- Antonakoudis A, Kyriakoudi S A, Chatzi D, et al. Genetic Basis of Motor Neuron Diseases: Insights, Clinical Management, and Future Directions[J]. International Journal of Molecular Sciences, 2025, 26(10): 4904.