Roluperidone (MIN-101)

In Development for the Treatment of Negative Symptoms of Schizophrenia

Roluperidone is a compound that has been shown to block serotonin, sigma and α-adrenergic receptors that are involved in the regulation of mood, cognition, sleep and anxiety. We are developing roluperidone to treat the negative symptoms of patients with schizophrenia.

Roluperidone has been designed to block a specific subtype of serotonin receptor called 5-HT_2A. When 5-HT_2A is blocked, certain symptoms of schizophrenia, such as hallucinations, delusions, agitation and thought and movement disorders, as well as the side effects associated with antipsychotic treatments, can be minimized. Additionally, blocking 5-HT_2A promotes slow wave sleep, a sleep stage often disrupted in patients with schizophrenia. Roluperidone has also been designed to block a specific subtype of sigma receptor called sigma₂, which is involved in movement control, psychotic symptom control and learning and memory. Blocking sigma₂, along with blocking the α‑adrenergic subtypes α_1A, and to a lesser extent α_1B, also increases calcium levels in neurons in the brain, which can improve memory. Pre-clinical findings provide evidence of the effect of roluperidone on Brain-Derived Neurotrophic Factor (“BDNF”), which has been associated with neurogenesis, neuroplasticity, neuroprotection, synapse regulation, learning and memory.

We believe the scientifically supported and innovative mechanisms of action of roluperidone may potentially address the unmet needs of schizophrenic patients, which include negative symptoms and cognitive impairment, without the side effects of existing therapies. Negative symptoms are lifelong debilitating symptoms and include: asociality, or the lack of motivation to engage in social interactions; anhedonia, or the inability to experience positive emotions; alogia, or failure to engage in normal conversation; avolition, or loss of energy and interest in activities; and blunted affect, or diminished emotional expression. We plan to seek approval of roluperidone initially as a first line treatment of negative symptoms in patients diagnosed with schizophrenia, and we also may study its use to treat all aspects of the disease, including positive symptoms and relapse prevention. We believe that roluperidone, if approved, could treat the majority of patients diagnosed with schizophrenia. An estimated 69% of patients diagnosed with schizophrenia have negative symptoms, with at least 42% of patients diagnosed with schizophrenia having prominent negative symptoms.

Beyond schizophrenia, we believe roluperidone may possess therapeutic utility in brain disorders where negative symptoms are a core feature of the disease associated with a range of poor clinical outcomes. These potential indications include apathy in dementia, for which we have filed an Investigational New Drug (“IND”) application, the majority of schizophrenia spectrum and other psychotic disorders, autism spectrum disorders, Alzheimer’s disease, Parkinson’s disease and depression.

Publications

Efficacy and Safety of Roluperidone for the Treatment of Negative Symptoms of Schizophrenia
Authors: Michael Davidson, Jay Saoud, Corinne Staner, Nadine Noel, Sandra Werner, Elisabeth Luthringer, David Walling, Mark weiser, Philip D. Harvey, Gregory P. Strauss, Remy Luthringer 

Published:  25 February 2022

Network Analysis Indicates That Avolition Is the Most Central Domain for the Successful Treatment of Negative Symptoms: Evidence From the Roluperidone Randomized Clinical Trial
Authors: Gregory P Strauss, Farnaz Zamani Esfahlani, Hiroki Sayama, Brian Kirkpatrick, Mark G Opler, Jay B Saoud, Michael Davidson, Remy Luthringer

Published: 28 January 2020, PDF

Effects of Roluperidone (MIN-101) on two dimensions of the negative symptoms factor score: Reduced emotional experience and reduced emotional expression
Authors: Philip D. Harvey, Jay B. Saoud, Remy Luthringer, Svetlana Moroz, Yuliya Blazhevych, Cristinel Stefanescu, Michael Davidson

Published: January 2020, PDF

Letter to the Editor: Personal and social adjustment effects of roluperidone in patients with schizophrenia and negative symptoms: Results from an exploratory outcome of a randomized placebo-controlled trial
Authors: Jonathan Rabinowitz, Stefan Badescu, Pavel Palamarchuk, Viktor Filyk, Anatolii Voloshchuk, Vadym Rud, Ellina Melnyk, Andrii Skrypnikov, Michael Davidson, Jay Saoud, Remy Luthringer

Published: 4 June 2019, PDF

Cognitive Effects of MIN-101 in Patients With Schizophrenia and Negative Symptoms: Results From a Randomized Controlled Trial
Authors: Richard S. E. Keefe, Philip D. Harvey, Anzalee Khan, Jay B. Saoud, Corinne Staner, Michael Davidson, Remy Luthringer

Published: May/June 2018

The brief negative symptom scale (BNSS): Sensitivity to treatment effects
Authors: Brian Kirkpatrick, Jay B Saoud, Gregory P Strauss, Anthony O Ahmed, Kazunori Tatsumi, Mark Opler, Remy Luthringer, Michael Davidson

Published: 21 December 2017, PDF

Efficacy and Safety of MIN-101: A 12-Week Randomized, Double-Blind, Placebo-Controlled Trial of a New Drug in Development for the Treatment of Negative Symptoms in Schizophrenia
Authors: Michael Davidson, Jay Saoud, Corinne Staner, Nadine Noel, Elisabeth Luthringer, Sandra Werner, Joseph Reilly, Jean-Yves Schaffhauser, Jonathan Rabinowitz, Mark Weiser, Remy Luthringer

Published: 28 July 2017, PDF