Methods of treating psychosis and schizophrenia based on polymorphisms in the cntf gene

Abstract

This invention relates to the use of the association between the 103 G>A polymorphism in the CNTF gene to determine antipsychotic treatment strategies in patients with psychotic disorders.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention belongs to the fields of pharmacology, medicine and medicinal chemistry and provides methods to treat psychotic conditions including schizophrenia and related conditions. In particular, this invention relates to the use of genomic analysis to determine a patient's responsiveness to antipsychotic medication including lloperidone and methods to determine optimal treatment strategies. 2. Description of the Related Art Ciliary Neurotrophic Factor (CNTF) was originally known as a survival factor for chick ciliary neurons in vitro but has more recently shown to be a survival factor for different neuronal cell types. CNTF is involved with the prevention of degeneration of motor axons and is a member of the interleukin-6 cytokine family. Barbin et al. used a survival assay for neurons from chick embryonic ciliary ganglia to report the neurotrophic activity of CNTF from chick eye. See, Barbin, G et al., J. Neuroc...

AI Technical Summary

Benefits of technology

The present invention answers this need by providing methods for treating a patient suffering from or susceptible to a psychotic disorder, including but not limited to schizophrenia and mood disorders with psychotic symptoms, comprising determining for the two copies of the CNTF gene present in the individual, the identity of the nucleotide pair at the polymorphic site 103 G>A, (the CNTF gene is located on 11q12.2 the polymorphism is 103 G>A in GenBank sequence X55890 (Version 1)). This nucleotide variation results in the creation of a new splice acceptor site, an altered mRNA and a resultant aberrant protein (FS63 TER), see, Pub Med ID No. 9285965. The determination of treatment is based on the knowledge that if both nucleotide pairs are G or if both nucleotide pairs are A then the individual will be responsive to treatment with antipsychotic medications including but not limited to lloperidone. If one nucleotide pair is A and one is G it can be expected that the individual will be less responsive to antipsychotic medications, including but not limited to lloperidone and may require a higher dose or an adjunctive therapy in addition to, or instead of an antipsychotic. On the basis of this information the individual can be administered an effective amount of an appropriate antipsychotic medication designed to minimise side effects and to maximise response and patient compliance.

Problems solved by technology

Psychoses exact a tremendous emotional and economic toll on the patients, their families, and society as a whole.

Unfortunately, neuroleptics-resistant negative symptoms account for most of the social and vocational disability caused by schizophrenia.

However, up to now there has been no means, other than trial and error, to determine which patients will respond to an antipsychotic agent and what dose level a given patient may require to produce a therapeutic response without severe side effects.

Since all antipsychotic agents, even the newer atypical ones, have significant side effects including extrapyramidal symptoms, such as rigidity, tremor, bradykinesia (slow movement), and bradyphrenia (slow thought), as well as tardive dyskinesias and dystonias this “trial and error” period could be time consuming, unpleasant and even dangerous for the patient and increased the likelihood of non-compliance.

These side effects and toxic effects are dose dependent.

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