Lower Motor Neuron Diseases (LMND)
Lower motor neuron diseases (LMND) represent an uncommon group of neurological disorders which affect the motor neurons located in the spinal cord or brainstem. Protheragen, with its vast experience on therapy development in LMNDs, is strategically positioned to help clients move from the research phase into therapy development and commercialization with the necessary support and solutions designed specifically for clients.
Overview of Lower Motor Neuron Diseases (LMND)
Lower motor neuron disorders (LMND) include a set of neurodegenerative diseases due to atrophy of the motor neurons in the spinal cord and the brainstem which leads to a progressive weakness of the muscles, paralysis, and atrophy of the muscles. Unlike upper motor neuron disorders, neuromuscular diseases (LMND) affect primarily the alpha motor neurons which leads to blockage of transmission across a muscle and therefore manifest in severe symptoms.
Fig.1 Clinical signs of upper motor neuron (UMN) and lower motor neuron (LMN) involvement according to body regions. (Vidovic M, et al., 2023)
Pathogenesis of Lower Motor Neuron Diseases (LMND)
The pathogenesis of lower motor neuron diseases (LMND) involves the progressive degeneration of spinal and brainstem motor neurons due to genetic mutations, disrupted RNA metabolism, protein aggregation, impaired axonal transport, and mitochondrial dysfunction. Secondary mechanisms include neuroinflammation, glial activation, and excitotoxicity from aberrant glutamate signaling. These pathways collectively lead to muscle denervation, atrophy, and paralysis.
Fig.2 Molecular mechanisms and pathophysiology of motor neuron diseases. (Trabacca A, et al., 2024)
Therapeutic Development for Lower Motor Neuron Diseases (LMND)
| Drug Name | Indications | Mechanism of Action | NCT Number | Research Phase |
| Nusinersen | Spinal Muscular Atrophy (SMA) | ASO modulating SMN2 splicing to increase functional SMN protein | NCT05789758 | Approved |
| Onasemnogene Abeparvovec | Spinal Muscular Atrophy (SMA) | AAV9-based gene therapy that delivers a functional copy of the SMN1 gene to motor neurons via intravenous infusion | NCT02122952 | Approved |
| Rosuvastatin | Friedreich Ataxia | HMG-CoA reductase inhibitor, may reduce oxidative stress and improve frataxin function | NCT02705547 | Phase II/III |
| DT-216P2 | Friedreich Ataxia | Delivering a functional FXN (frataxin) gene to deficient cells. | NCT06874010 | Phase I/II |
| Goserelin | Kennedy's Disease | Suppressing testosterone production by downregulating pituitary gonadotropin release. | NCT00851461 | Phase II |
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 is leading the way in diagnostics and therapeutics of rare lower motor neuron diseases (LMND). We carefully identify relevant biomarkers of LMND for the creation of in vitro diagnostic (IVD) kits. Our tailored therapeutic development services aim to construct novel therapies targeting the very origins of LMND. These therapeutic agents undergo thorough refinement and validation in specialized disease models to ensure precision in the treatment of these disorders.
Types of Rare Lower Motor Neuron Diseases (LMND)
| A-M | |
| Benign Monomelic Amyotrophy Botulism Distal Hereditary Motor Neuropathy Flail Arm Syndrome and Flail Leg Syndrome Friedreich Ataxia |
Hereditary Bulbar Palsy Hereditary Motor Neuropathies (HMN) Monomelic Amyotrophy Multifocal Motor Neuropathy Myasthenia Gravis |
| N-Z | |
| Neuromuscular Junction Disease Post Irradiation Lumbosacral Radiculopathy Posterior Horn Cell Disorders Post-Polio Syndrome Progressive Bulbar Palsy |
Progressive Muscular Atrophy (PMA) Spinal Bulbar Muscular Atrophy (Kennedy's Disease) Spinal Muscular Atrophy (SMA) Spinocerebellar Ataxia (SCA) |
Therapeutic Development Services
By Molecule Types
At Protheragen, we overcome bottlenecks in lower motor neuron diseases (LMND) drug development through comprehensive and multimodal drug development platforms to accelerate therapies from discovery to clinical translation.
By Mechanism of Action
Protheragen specializes in developing customized neurotherapeutic drugs targeting the underlying pathological mechanisms of lower motor neuron diseases (LMND), leading to groundbreaking treatment solutions.
Disease Model Development Services
In Vitro Model
Development
Focusing on end-to-end therapeutic development for challenging neurological diseases, Protheragen also constructs advanced blood-brain barrier (BBB) models to facilitate optimization studies of central nervous system (CNS) drug delivery. We specialize in providing comprehensive preclinical research services covering pharmacodynamics (PD), pharmacokinetic (PK), and toxicology studies to support the development and regulatory approval of potential therapies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Vidovic M, Müschen L H, Brakemeier S, et al. Current state and future directions in the diagnosis of amyotrophic lateral sclerosis[J]. Cells, 2023, 12(5): 736.
- Trabacca A, Ferrante C, Oliva M C, et al. Update on Inherited Pediatric Motor Neuron Diseases: Clinical Features and Outcome[J]. Genes, 2024, 15(10): 1346.