Rare Motor Neuron Diseases (MND)
Rare motor neuron diseases (MND) pose numerous therapeutic challenges. Committed to precision and efficacy, we dedicate ourselves to delivering custom diagnostic and therapeutic development services to our clients. Whether you are exploring novel therapeutic avenues, validating potential drugs, or navigating the intricacies of bringing a therapy to market, our team is here to support and assist you every step of the way.
Introduction to Rare Motor Neuron Diseases
Rare motor neuron diseases (MND) constitute a cluster of neurological conditions marked by the gradual deterioration of motor neurons, resulting in muscle weakness, wasting, and compromised motor abilities. Based on the location of the affected neurons, they can be classified into upper motor neuron diseases (UMND), lower motor neuron diseases (LMND), and combined upper and lower motor neurone disorders.
- Upper motor neuron diseases (UMND) primarily affect the motor neurons located in the cerebral cortex, brainstem, and spinal cord. These diseases disrupt the pathway between the brain and the spinal cord, leading to impairments in voluntary muscle control and coordination.
- Lower motor neuron diseases (LMND) primarily affect the motor neurons located in the anterior horn cells of the spinal cord and the cranial nerve nuclei in the brainstem. These diseases directly impact the motor neurons responsible for muscle movement, leading to weakness and atrophy.
- Mixed motor neuron diseases involve a combination of upper and lower motor neuron involvement, resulting in a complex presentation that exhibits characteristics of both UMND and LMND.
Fig. 1 Damaged spinal motor neurons in amyotrophic lateral sclerosis. (Ciervo Y, et al.,
2017)
Pathogenesis of Rare Motor Neuron Diseases
The pathogenesis of rare motor neuron diseases (MND) involves complex mechanisms that lead to motor neuron degeneration. Some common underlying factors include genetic mutations, protein misfolding and aggregation, mitochondrial dysfunction, etc. Understanding the complex interplay between these factors and identifying the specific molecular pathways involved in each disease is critical to developing targeted therapeutics and interventions to slow or stop the progression of these devastating diseases.
Genetic Mutations
Numerous MNDs are genetically rooted, where mutations in particular genes are pivotal in the progression of the diseases. For instance, spinal muscular atrophy (SMA) arises from mutations in the SMN1 gene, leading to a scarcity of the survival motor neuron (SMN) protein.
Protein Aggregation
In certain MNDs, abnormal protein aggregation within neurons can contribute to neurodegeneration. This phenomenon is seen in conditions like amyotrophic lateral sclerosis (ALS), where misfolded proteins such as TDP-43 accumulate in affected motor neurons.
Mitochondrial Dysfunction
Impaired mitochondrial function, which is crucial for energy production and maintaining cellular homeostasis, has been implicated in the pathogenesis of motor neuron diseases. Disorders such as primary lateral sclerosis have been associated with irregularities in mitochondrial function.
Therapeutic Development for Rare Motor Neuron Diseases
Due to the complexity of rare motor neuron diseases (MND) and the limited affected population, the development of innovative therapies faces significant challenges. However, advancements in gene therapy, small molecule therapy, and stem cell therapeutics have opened up new avenues for therapeutic development. In 2023, the market size of MND therapeutics was valued at $9.51 billion, expected to reach $19.56 billion by the end of 2036, with a projected compound annual growth rate of approximately 5.7%.
Table. 1 A partial list of approved drugs for rare motor neuron diseases.
| Drugs | Types of Therapy | Targeted Diseases | Developmental Stage |
| Onasemnogene abeparvovec | Gene Therapy | Spinal Muscular Atrophy (SMA) | Approved |
| Risdiplam | Small Molecule Therapy | Spinal Muscular Atrophy (SMA) | Approved |
| Edaravone | Free Radical Scavenger | Amyotrophic Lateral Sclerosis (ALS) | Approved |
| Riluzole | Glutamate Modulator | Amyotrophic Lateral Sclerosis (ALS) | Approved |
| Eteplirsen | Exon Skipping Therapy | Duchenne Muscular Dystrophy (DMD) | Approved |
Our Services
Our company is committed to advancing the development of diagnostics and therapies for rare motor neuron diseases (MND) through a wide array of services. By pinpointing biomarkers, we meticulously craft in vitro diagnostic (IVD) kits to enable early disease identification. Leveraging extensive in vitro and animal models, we are dedicated to spearheading groundbreaking therapeutics for these intricate conditions.
Disease Model Development Services
In Vitro Models
- Primary Neuronal Cultures
- Midbrain Organoids
- Neuronal Network Microfluidic Models
- Motor Neuron Cultures
- Spinal Cord Organoids
- Motor Neuron-Muscle Co-culture Microfluidic Models
Animal Models
- Brain Injury Models
- Spinal Cord Injury Models
- Transgenic Models
- Knock-in Models
- Knock-out Models
- And More
Therapeutic Development Services
By Molecule Types
By Mechanism of Action
- Neuroprotective Agent Development
- Glutamate Modulator Development
- Antioxidant Development
- Mitochondrial Support Agent Development
- Protein Misfolding Inhibitor Development
- Excitotoxicity Inhibitor Development
Multiple Rare Motor Neuron Disease Research
Upper Motor Neuron Diseases (UMND)
Lower Motor Neuron Diseases (LMND)
Mixed Motor Neuron Diseases
By building precise animal models, we can investigate the mechanisms of rare motor neuron diseases and conduct pharmacology, pharmacokinetic (PK), and toxicology studies on candidate therapies to confirm their efficacy and safety. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Ciervo Y, Ning K, Jun X, et al. Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis[J]. Molecular neurodegeneration, 2017, 12: 1-22.