SCHIZOPHRENIA
DISEASE OVERVIEW:
Schizophrenia is a chronic, severe and disabling condition that affects almost 1% of the world's population and is believed to be caused by a combination of environmental and genetic factors. In addition to the enormous hardships endured by patients themselves, the burden on families and caregivers is immense. The cost of treatment and loss of productivity in the U.S. has been estimated at $60 billion annually. As a chronic condition, management of the disease and its symptoms is a life-long process for patients and their caregivers.
SYMPTOMS:
The symptoms associated with schizophrenia are often described within three categories: positive symptoms (paranoia, hallucinations and delusions), negative symptoms (loss or decrease in ability to speak and express emotion and social withdrawal), and cognitive symptoms (impairments in working memory, executive functioning and other cognitive functions).
CURRENT TREATMENT APPROACHES:
The greatest success of current treatments has been in treating positive symptoms, and most currently-approved therapies have shown limited success with regard to negative and cognitive symptoms. In part because of this, many psychiatrists and other experts are convinced that the key to improving the lives of patients with schizophrenia - and allowing patients to better manage their condition - lies in addressing the negative symptoms and the cognitive deficits associated with schizophrenia. It may be that it is with respect to negative and cognitive symptoms that glutamate modulation and other novel therapies hold their greatest promise.
The high cost of schizophrenia care arises, in part, from limited advances in treatment options. Virtually all of the major antipsychotics approved by the FDA in the past fifty years act primarily on dopamine and/or serotonin receptor function. Unfortunately, despite 2009 US antipsychotic sales of $14.6 billion, these antipsychotics produce severe side effects and are not effective in treating the full range of symptoms associated with schizophrenia. Moreover, despite these shortcomings, a significant percentage of development projects directed towards schizophrenia and related symptoms are still focused on dopamine and/or serotonin receptor function.
Despite the immense impact of the disease, patients and their physicians confront approved treatment options which do not successfully address the full range of symptoms and often give rise to significant side-effects. This has resulted in a treatment environment marked by poor overall compliance. For example, in a study initiated by the NIMH and published in the New England Journal of Medicine (September 22, 2005, Vol. 353), the treatment of 1,493 schizophrenic patients using first and second generation antipsychotics was followed. Of those patients, an overall 74% discontinued medication before 18 months, largely due to inefficacy or intolerable side effects. Moreover, the time to discontinuation was found to be similar among the first generation anti-psychotics and second-generation agents.
HOPE THROUGH RESEARCH:
In the past, drugs used to treat schizophrenia or other psychiatric conditions have typically been “discovered” serendipitously. At Promentis, we realize that a key in developing more effective medications is to target the pathology that underlies the disease, especially the pathological brain functioning that gives rise to negative symptoms and cognitive deficits associated with schizophrenia. This is a difficult endeavor, in part because of the complexity of the changes that contribute to these symptoms. Studies conducted over the past ten years have repeatedly implicated abnormal functioning of the neurochemical glutamate as an important part of the pathophysiology of schizophrenia. Specifically, these studies suggest that an increase in the activity of glutamate at NMDA receptors, a key target for glutamate, is needed to treat schizophrenia. Compelling data also suggest that a decrease in the activity of glutamate at AMPA receptors, a second key target for glutamate, would be therapeutically beneficial. In addition, other studies suggest that deficiencies in key cellular chemicals, including the critical antioxidant glutathione, are present in schizophrenia and may also represent key pathological changes. Thus, a more effective approach must target a complex constellation of changes in brain functioning.
At Promentis, we firmly believe that superior treatments require better science. Our goal of developing an effective first in class medication is based on research that we believe more completely addresses the pathological changes in brain functioning that give rise to schizophrenia, and which may be implicated in other disease states (which research is coupled with extensive intellectual property coverage). Within this framework, Promentis is aggressively embarking on an effort to redefine what is possible in the treatment of schizophrenia and other psychiatric disorders.
ADDITIONAL SITES:
More information regarding schizophrenia, its treatment and related issues of concern to patients and their caregivers can be obtained from the National Alliance for Research on Schizophrenia and Depression (NARSAD) www.narsad.org, The National Alliance on Mental Illness (NAMI) www.nami.org, and the National Institutes of Health (NIMH) www.nimh.nih.gov.
