Question

As the scientific director of a pharmaceutical company, you are interested in developing a drug that would prevent the cataplectic attacks experienced by narcoleptic humans. Based on the series of scientific research articles published about narcolepsy using dogs, rodents, and humans, how should your target drug function?

Answer 1

With development of animals model for conducting research on Narcolepsy (a form of sleep disorder), following was observed -

a) Narcolepsy is caused by imbalance between monoaminergic and cholinergic systems

b) It is caused due to orexin neurotransmission deficiency

In case of canine, it occurred primarily due to loss of Ox2R function or due to loss of orexin neuron. In case of rodent (mouse), this disease was found to be linked with loss of orexin gland, or loss of orexin receptor, post natal degeneration of orexin neuron or inhibition of the gene expression of orexin or its receptors. However, in case of humans, it was found that Narcolepsy is due to the presence of leukocyte antigen allele. This allele is essential for antigen processing and biomarkers for auto immune diseases

Drug –

Only pharmacological treatment is possible where drugs causing stimulation in CNS and treating cataplexy have been used. Thus, amphetamine (CNS stimulant) + Imipramine (antidepressant) can be used.

Currently, sodium oxybate is being used to treat narcolepsy as it can treat EDS, cataplexy and disturbed nocturnal sleep effectively