Minerva Neurosciences Announces Findings Showing Effect of Roluperidone on Brain-Derived Neurotrophic Factor (BDNF)
Data from this study are being presented today at the
Dysregulation of BDNF has been described in the pathophysiology of schizophrenia and several other neuro-psychiatric disorders. Therefore, in addition to the known neurotransmitter pathways targeted by roluperidone, particularly the serotoninergic 5-HT2A and the sigma2 pathways, the effect of roluperidone on BDNF suggests that this investigational compound may have the potential for disease modification and improved neuroplasticity.
“These findings, along with the clinical results seen during the phase 2b study, suggest the potential of roluperidone to change the overall course of schizophrenia,” said Dr.
BDNF is a member of a family of proteins called neurotrophins that play an important role in the formation and function of neural connections. An emerging body of evidence has pointed to a link between BDNF and CNS disorders. Epigenetic changes in the BDNF gene have been shown to be related to the pathophysiology of schizophrenia, and the reduced expression of BDNF has been identified in the frontal cortex and hippocampus of the brain in patients with schizophrenia.4
Researchers believe that lower than normal levels of BDNF may affect the pathogenesis of schizophrenia by contributing to altered brain development and abnormalities in neuroplasticity and synaptic function. These disturbances may explain certain morphological and neurochemical characteristics in the brains of patients with schizophrenia.5
Furthermore, a functional polymorphism in the BDNF gene has been observed to interact with environmental factors in the development of psychoses including schizophrenia and bipolar disorders.6 Additional studies have found an association between higher levels of BDNF and improved cognitive function in schizophrenic patients and improved neuropsychological function.7
Roluperidone is a drug candidate with equipotent affinities for 5‑hydroxytryptamine-2A (5-HT2A) and sigma2 and at lower affinity levels, α1-adrenergic receptors. Roluperidone exhibits no affinity for dopaminergic, muscarinic, cholinergic and histaminergic receptors. Roluperidone has no direct dopaminergic post-synaptic blocking effects, known to be involved in some side effects like extrapyramidal symptoms, sedation, prolactin increases and weight gain.
A pivotal Phase 3 clinical trial is ongoing with roluperidone as monotherapy for negative symptoms in patients diagnosed with schizophrenia. Approximately 500 patients are expected to be enrolled at approximately 60 clinical sites in the U.S. and Europe. Top-line results from the 12-week double blind phase of this trial are expected in the first half of 2019.
Forward-Looking Safe Harbor Statement
This press release contains forward-looking statements which are subject to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts, reflect management’s expectations as of the date of this press release, and involve certain risks and uncertainties. Forward-looking statements include statements herein with respect to the timing and scope of current clinical trials and results of clinical trials with roluperidone, seltorexant, MIN-117 and MIN-301; the timing and scope of future clinical trials and results of clinical trials with these compounds; the clinical and therapeutic potential of these compounds; our ability to successfully develop and commercialize our therapeutic products; the sufficiency of our current cash position to fund our operations; and management’s ability to successfully achieve its goals. These forward-looking statements are based on our current expectations and may differ materially from actual results due to a variety of factors including, without limitation, whether roluperidone, seltorexant, MIN-117 and MIN-301 will advance further in the clinical trials process and whether and when, if at all, they will receive final approval from the
VP, Investor Relations/
1 BDNF and schizophrenia: from neurodevelopment to neuronal plasticity, learning and memory, R. Nieto et al, Frontiers in Psychiatry,
2 Childhood trauma interacted with BDNF Val66Met influence schizophrenic symptoms, Xiao-jiao Bi et al, Medicine, http://dx.doi.org/10.1097/MD.0000000000010160
3 Pridopidine activates neuroprotective pathways impaired in Huntington Disease, M. Geva et al, Human Molecular Genetics, 2016, Volume 25 Number 18, doi:10.1093/hmg/ddw238
4 Effects of Antipsychotic Drugs on the Epigenetic Modification of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampi of Chronic Restraint Stress Rats,
5 BDNF and schizophrenia: from neurodevelopment to neuronal plasticity, learning and memory, R. Nieto et al, Frontiers in Psychiatry,
6 Childhood trauma interacted with BDNF Val66Met influence schizophrenic symptoms, Xiao-jiao Bi et al, Medicine, http://dx.doi.org/10.1097/MD.0000000000010160
7 BDNF (brain-derived neurotrophic factor) serum levels in schizophrenic patients with cognitive deficits, N. Utami et al, doi:10.1088/1755-1315/125/1/012181
Source: Minerva Neurosciences, Inc