Neurolathyrism
Spastic paraparesis is the main indicator of a disorder called neurolathyrism. Building on our foundational work in neurolathyrism research, Protheragen is leading the way in developing new therapies to improve the management of neurolathyrism. As your trusted collaborator in neurolathyrism therapeutic research, we are committed to supporting your research project from every angle.
Introduction to Neurolathyrism
Neurolathyrism is an irreversible degenerative disorder of the nervous system that results from the persistent consumption of Lathyrus sativus (grass pea), especially amongst nutritionally deprived and famine-stricken populations. The disorder manifests as spastic paraparesis, hypertonia, and enduring lower-limb paralysis resulting from upper motor neuron atrophy. Outbreaks have been recorded historically in Ethiopia, India, and Bangladesh, where grass pea is a neurotoxic staple crop that withstands drought.
Fig.1 Overview of neurolathyrism onset. (Singh V, et al., 2023)
Pathogenesis of Neurolathyrism
The neurotoxin β-N-oxalyl-L-α, β- diaminopropionic (β-ODAP) is responsible for the pathogenesis of neurolathyrism and functions by glutamate simulation and over stimulation of AMPA/kainate receptors which causes persistent neuronal depolarization as well as calcium overload. Excitotoxicity causes oxidative stress along with mitochondrial dysfunction and activation of certain proteases such as calpain which leads to motor neuron degeneration that is irreversible. Prolonged exposure leads to damage of the corticospinal tract, Betz cell loss in the motor cortex, and death of anterior horn cells in the spinal cord, leading to spastic paraplegia.
Fig.2 Molecular mechanisms of neurolathyrism. (Tan R Y, et al., 2017)
Therapeutic Development for Neurolathyrism
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Tolperisone HCl | Blocks voltage-gated sodium channels and modulates calcium influx, reducing spasticity. | Voltage-gated Na⁺/Ca²⁺ channels | Approved |
| Gabapentin | Binds to α2δ subunit of voltage-gated calcium channels, decreasing excitatory neurotransmission. | Neuronal α2δ-1 (CACNA2D1) subunit | Approved |
| Perampanel | Non-competitive AMPA receptor antagonist, inhibiting glutamate-induced excitotoxicity. | AMPA-type glutamate receptors (GRIA1-4) | Approved |
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, as a leader in the upper motor neuron disease (UMND) research, offers complete preclinical services to aid in the translation of neurolathyrism therapeutics from discovery to validation. Our platforms are aimed towards disease modeling of BOAA-induced excitotoxicity as well as duplicating the hallmark corticospinal tract degeneration seen in neurolathyrism.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- Induced Disease Model: Experimental neurolathyrism can be reliably induced in ascorbic acid-dependent animals (e.g., guinea pigs, primates) by combining subclinical ascorbic acid deficiency with Lathyrus sativus seed or extract feeding.
Focusing on end-to-end therapeutic development for neurolathyrism, 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
- Singh V, Mishra Y, Mishra V N. Existence of Lathyrus Beyond Lathyrism[J]. Journal of Preventive, Diagnostic and Treatment Strategies in Medicine, 2023, 2(4): 208-217.
- Tan R Y, Xing G Y, Zhou G M, et al. Plant toxin β-ODAP activates integrin β1 and focal adhesion: A critical pathway to cause neurolathyrism[J]. Scientific Reports, 2017, 7(1): 40677.