Project Summary

Jeffrey A. Lieberman, M.D. (Distinguished Investigator 2007) of Columbia University, aims to do a small clinical trial of a drug called AL-108 in individuals with chronic schizophrenia already receiving antipsychotic treatment to determine if the additional medication enhances their cognition. Approximately 75 percent of patients with schizophrenia have deficits in at least two cognitive domains; 90 percent, in at least one domain. Cognitive deficits antedate clinical onset of illness, may worsen over time, and are correlated with functional outcome. Because current antipsychotics are generally unable to reverse the dysfunction, new drugs that target schizophrenia’s cognitive dysfunction is a major focus of investigation. NAP, an eight-amino acid active derivative of activity-dependent neuroprotective protein, ADNP, has demonstrated substantial neuroprotective effects in animal models of CNS insult and in neuropsychiatric disorders, NAP has improved short-term memory in normal, middle age rodents and in animal models of psychiatric disease. NAP is believed to work by binding brain tubulin, promoting microtubule reorganization, and increasing synaptogenesis in hippocampal and cortical regions; thus it may be affect synaptic plasticity by promoting synaptic reconnections after injury in the mature brain. AL-108 (in development by Allon Therapeutics for neurodegenerative conditions, such as Alzheimer's disease), is an intranasal formulation of NAP. A Phase-IA randomized, double-blinded, placebo-controlled, escalating dose study of AL-108 in which single doses up to 15 mg were administered to 25 individuals has been completed. The drug was well tolerated with headache being the most common minor side effect. In this NARSAD proposal, Dr. Lieberman is seeking funding to conduct a 12-week randomized, double-blinded, placebo-controlled, proof-of-concept study of two fixed doses of daily AL-108 added to stable, antipsychotic treatment in individuals with chronic schizophrenia. Dr. Lieberman’s primary hypothesis is that those taking AL-108 will exhibit greater cognitive improvement from baseline compared to the antipsychotic/placebo group. Positive findings may lead to a better understanding of schizophrenia and be the basis for additional funding support for research on a possible new treatment for schizophrenia’s cognitive dysfunction.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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