Konzo
People in developing countries who eat poorly processed cassava suffer from Konzo, a neurotoxic disorder. Protheragen uses advanced research on the causes of Konzo to create precision animal models and targeted therapies, thereby speeding up preclinical drug development. We aim to provide comprehensive, dependable support throughout every stage of your therapeutic development journey.
Introduction to Konzo
Konzo is an upper motor neuron disorder (UMND) which is non-progressive and caused by toxins, and is only found in sub-Saharan Africa. It is characterized by spastic paraparesis which occurs suddenly. This disease mainly impacts children and women in rural communities that depend on cassava (Manihot esculenta) for food during droughts and famines. Epidemiological studies report outbreak-associated prevalence rates of about 5% in certain regions. These outbreaks are associated with poorly detoxified cassava.
Fig.1 From individual susceptibility to the spectrum of Konzo. (Nzwalo H, Cliff J., 2011)
Pathogenesis of Konzo
The pathogenesis of Konzo involves the ingestion of inadequately processed cassava, which contains cyanogenic glycosides. The conversion of these compounds to cyanide in the body will result in cyanide toxicity. The damage cyanide inflicts upon the body is selective, targeting motor neurons in the spinal cord which leads to the distinctive rapid onset spastic paralysis affecting the lower limbs encountered in Konzo.
Therapeutic Development for Konzo
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Hydroxocobalamin | Binds cyanate/cyanide to form non-toxic cyanocobalamin, preventing mitochondrial toxicity. | Cyanide ions, cytochrome c oxidase | Phase II |
| Sulforaphane | Activates Nrf2 pathway, upregulating antioxidant genes (HO-1, NQO1) to counteract oxidative stress in motor neurons. | Nrf2-Keap1 system | Preclinical |
| Epothilone D | Microtubule-stabilizing agent that restores axonal transport in corticospinal tracts damaged by cyanate. | β-tubulin, microtubule-associated proteins | 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 Protheragen, we provide comprehensive services from biomarker identification to the development of targeted therapies for Konzo, a neurotoxic disorder which poses unique challenges for researchers. With our knowledge in disease modeling, patient-derived iPSCs, genetically engineered models, and novel blood-brain barrier (BBB) models, we offer rigorous assessment of drug delivery and neuroprotective efficacy.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model
Development
Development
- Acetone Cyanohydrin Induced Models: Acetone cyanohydrin was added to the drinking water of experimental rats to induce disease symptoms.
- Cassava Feeding Models: The rats were fed a cassava diet rich in cyanogenic glycosides, similar to the diet humans associate with Konzo.
To advance the commercialization of novel therapies for Konzo, 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
- Nzwalo H, Cliff J. Konzo: from poverty, cassava, and cyanogen intake to toxico-nutritional neurological disease[J]. PLoS neglected tropical diseases, 2011, 5(6): e1051.