Treatment of schizophrenia

Abstract

The present invention relates to a method of treating schizophrenia in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a selective D3 antagonist, wherein said subject has at least one negative symptom (NS) among the following core negative symptoms in PANSS: Blunted Affect (N1), Emotional Withdrawal (N2), Poor Rapport (N3), Passive withdrawal (N4), and Lack of Spontaneity (N6); with moderate or higher severity. Methods for improving the probability of success and / or the effect of a treatment of schizophrenia in a subject in need thereof are also described.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application claims the benefit of priority to U.S. Provisional Application No. 62 / 581,249, filed on Nov. 3, 2017, which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0002]The present invention relates to a method of treating schizophrenia in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a selective D3 antagonist, wherein said subject has at least one negative symptom (NS) among the following core negative symptoms in PANSS: Blunted Affect (N1), Emotional Withdrawal (N2), Poor Rapport (N3), Passive withdrawal (N4), and Lack of Spontaneity (N6); with moderate or higher severity, wherein said moderate or higher severity corresponds to a score equal to 4 or higher before beginning of said treatment. Methods for improving the probability of success and / or the effect of a treatment of schizophrenia in a subject in need thereof are also descr...

AI Technical Summary

Benefits of technology

The inventors have discovered that a specific group of patients with schizophrenia respond better to treatment with a drug that targets a certain protein in the brain called D3. This is surprising because previous research had not identified this particular group of patients.

Problems solved by technology

The disorder is accompanied by significant social or occupational dysfunction, mainly related to the impairment of cognition with difficulties in memory, executive functions, slow processing speed, attention and concentration, as well as to the severity of negative symptoms.

Social problems, such as long-term unemployment, poverty and homelessness, are common.

Antipsychotics drugs however fail to significantly improve the negative symptoms and cognitive dysfunction in schizophrenia.

Although these medications produce improvement in the positive symptoms of schizophrenia, they often result in serious adverse effects, including extrapyramidal symptoms (EPS) (Schotte et al., Psychopharmacology, 1996, 124, 57-73) which are attributed to the blockade of D2 receptors in the striatal region of the brain.

Whether as a drug class the typical or atypical antipsychotics are better is debatable.

Given this pattern, it seems obvious that the mechanism of action of the currently available antipsychotics, by blocking the dopaminergic D2 receptors in both regions, is not optimal in the treatment of schizophrenia.

However, as determinants of treatment response are poorly understood, it is very difficult to address the heterogeneity of treatment effects.

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