Distal Hereditary Motor Neuropathy (dHMN)
Distal hereditary motor neuropathy (dHMN) affects primarily the motor functions of hands and feet. Protheragen has a professional team of researchers and scientists who work extensively on dHMN. They seek to be first in developing innovative treatments for dHMN, specifically seeking to fill gaps in existing therapeutic options and further advance precision medicine in this area.
Introduction to Distal Hereditary Motor Neuropathy (dHMN)
Distal hereditary motor neuropathy (dHMN) consists of a group of lower motor neuron (LMN) disorders with genetic diversity, marked by progressive weakening of muscles distally, muscle wasting, and sensory function impairment. In terms of clinical presentation, dHMN appears as asymmetric or symmetric hand and foot weakness that can begin anytime between childhood to adulthood, progressing at different speeds depending on the age of onset. More than 10 subtypes (dHMN I–X) have been described which differ based on mode of inheritance and causal genes.
Table 1 Some subtypes of distal hereditary motor neuropathy (dHMN).
| Subtypes | Inheritance | Mutant Gene | Age of Onset | Clinical Features |
| dHMN II | Autosomal Dominant (AD) | HSPB1 | Childhood/Adolescence | Slowly progressive distal weakness |
| dHMN V | Autosomal Dominant (AD) | GARS | Adolescence/Adulthood | Upper limb predominance, hand muscle atrophy |
| dHMN VI | Autosomal Recessive (AR) | IGHMBP2 | Infancy (<6 months) | Severe infantile-onset LMN degeneration, respiratory failure |
| dHMN VII | Autosomal Dominant (AD) | Unknown | Variable (childhood-adulthood) | Diaphragmatic weakness, distal muscle involvement |
Pathogenesis of Distal Hereditary Motor Neuropathy (dHMN)
Distal hereditary motor neuropathy (dHMN) arises from genetically mediated dysfunction of lower motor neurons through multiple interconnected pathological mechanisms involving axonal maintenance, protein quality control, and RNA metabolism. Mutations in genes encoding critical neuronal proteins such as GARS tRNA synthetase disrupt axonal transport and protein synthesis, while HSPB1 chaperone deficiencies lead to toxic protein aggregation and cellular stress. IGHMBP2 helicase defects impair RNA processing and mitochondrial function, particularly affecting motor neuron survival.
Fig.1 Pathological mechanisms of genes reported in hereditary motor neuropathy (HMN). (Bansagi B, et al., 2017)
Therapeutic Development for Distal Hereditary Motor Neuropathy (dHMN)
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Riboflavin |
|
Electron transport chain complexes I/II, glutathione reductase | Phase II/III |
| Epalrestat |
|
Aldose reductase, sorbitol dehydrogenase | Preclinical |
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 the forefront of lower motor neuron disease (LMND) research, Protheragen provides precision diagnostic and therapeutic development solutions for distal hereditary motor neuropathy (dHMN). We identify disease-specific biomarkers to support the development of in vitro diagnostic (IVD) kits to enable early diagnosis. Our advanced disease models faithfully replicate key physiological and pathological features, while proprietary blood-brain barrier (BBB) models are used to validate CNS-targeted therapeutics.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- HSPB8 knock-in model expresses mutant Hspb8 protein and exhibits peripheral nerve degeneration and severe muscle atrophy.
- HSPB8 knock-out (KO) model completely ablates HSPB8 expression to investigate its neuroprotective role in motor neuron survival.
To advance the commercialization of novel therapies for distal hereditary motor neuropathy (dHMN), Protheragen provides comprehensive pharmacodynamic (PD), pharmacokinetic (PK) and toxicology research services. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Bansagi B, Griffin H, Whittaker R G, et al. Genetic heterogeneity of motor neuropathies[J]. Neurology, 2017, 88(13): 1226-1234.