Robert J. Ferrante, PhD, MSProfessor of Neurological Surgery
Robert J. Ferrante, PhD, MS, joined the Department of Neurological Surgery in July of 2011.
Prior to coming to Pittsburgh, Dr. Ferrante spent over 20 years at Harvard Medical School and the Massachusetts General Hospital in Boston in anatomical and experimental neuropathology under the tutelage of Drs. Edward P. Richardson, Jr. and Joseph B. Martin, publishing a number of seminal findings associated with the etiology and progression of neurological conditions, with one series of studies leading to the novel discovery of selective neuronal vulnerability and sparing in Huntington’s disease. This work initiated and strengthened current hypotheses of cell death. In 1993 he accepted a position at the Boston University School of Medicine and the Boston Veterans Administration System, and served as a professor of neurology, laboratory medicine and pathology, psychiatry, and behavioral neuroscience, as well as the director of the Experimental Neuropathology and Translational Therapeutics Laboratory. Dr. Ferrante is a visiting professor in neuroscience at Amherst College. He received both his doctorate and bachelor degree from Boston University.
Dr. Ferrante has a wide-range of knowledge about the neuropathology and mechanisms of neurodegeneration in adult-onset neurological diseases, with more than 30 years experience in clinical and experimental neurology. He is considered an expert in the application of experimental models of disease and in bench to bedside translational studies. Over the past 20 years, Dr. Ferrante has developed an international reputation as having one of the premier translational programs for understanding pathophysiological mechanisms of neurological disease and for developing and characterizing therapeutic strategies for these conditions. His work has set the standard for others in the field. His laboratory has been a driving force in completing pre-clinical drug trials in mouse models of neurological disease and has acted as a conduit of therapeutic agents for direct translation to human clinical trials in Huntington’s disease and amyotrophic lateral sclerosis patients. This work has provided the basis for human trials using coenzyme Q10, creatine, cysteamine, sodium phenylbutyrate, amongst others. He has directed patient trails in the Veterans Administration and remains on multiple steering committees in advancing human clinical trials. He has had continuous grant funding since 1988 and is the holder of multiple patents.
A major goal of Dr. Ferrante’s current clinical research is to identify parallels in peripheral and central biomarker detection of disease and manifestations of neuronal dysfunction with translation to potential disease-modifying therapies that are being developed and evaluated in the clinical setting, especially in early stage disease. The goal is to create a data set of multiple markers that can be used with multivariate techniques to develop a unique biochemical signature relating to neurological diseases and to evaluate correlative biomarkers and biomarkers in response to therapy.
Dr. Ferrante’s work has garnered national and international recognition and he is regularly invited to lecture nationally and internationally. He sits on multiple boards and committees, and on grant review panels for the NIH and the VA, as well as disease-related foundations.
Dr. Ferrante is section editor for Molecular Basis of Disease at Biochimica et Biophysica, and a regular referee for many other journals. He has received multiple honorary awards for his research and dedication to patients with neurological conditions.
Dr. Ferrante's publications can be reviewed through the National Library of Medicine's publication database.
Professional Organization Membership:
Society for Neurosciences
International Basal Ganglia Society
World Federation of Neurology Research,
Huntington's Disease Society of America
Huntington’s Disease Study Group
Northeast Amyotrophic Lateral Sclerosis Consortium
ALS Therapy Alliance
Dr. Ferrante has continued working on two funded drug translational NIH and DOD applications in Huntington’s disease and amyotrophic lateral sclerosis, respectively, developing new pharmacotherapeutic agents for each disease focusing on the reduction of protein aggregation and ameliorating mitochondrial dysfunction. In each, he has identified specific chemical scaffolds that have shown marked efficacy in both in vitro cell and in vivo animal models of each disease. Dr. Ferrante is advancing select chemical compounds to IND studies and hope to have approval within the next year to perform first of kind human clinical trials using these agents. One compound, CMB-021805 extends disease survival well beyond any previous ALS mouse clinical trial (~31%), slowing functional motor performance decline, and markedly ameliorating the neuropathological phenotype observed in ALS mice.
In addition, Dr. Ferrante is continuing with two NIH grant applications that are observational human studies in Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS). The overall aims of these applications are to identify and follow biomarkers that correspond to early disease activity and disease progression in HD and ALS patients. He is examining and correlating potential disease biomarkers from both central nervous system and peripheral body fluids in HD and ALS patients, as compared to healthy control patients. These studies will determine whether peripheral biomarker profiles reflect changes observed in the central nervous system and how these markers correlate to the clinical symptoms in HD and ALS patients. He has evidence that there are correlative biomarkers in brain and blood within the same individuals and that these biomarkers change over disease progression. The detection of early manifest and progression biomarkers in HD and ALS will provide a major advance in determining how they may inform the human disease in clinical practice as prognostic outcome measures, providing potential novel direction regarding therapeutic strategies, and increasing the ability to detect an effect in human clinical trials.
Dr. Ferrante is also currently developing research assays into GLP assays for human clinical trials. He has advanced two such assays for Huntington’s disease that are currently being used in human clinical trails. One is an assay for creatine kinase that is significantly reduced in HD and can be demonstrated in both brain and blood. The blood assay is specific to creatine kinase found in the brain, CKBB. The other assay is for a select transcriptional chromatin modulator, H2A histone family, member Y (H2AFY), which is specific to HD and overexpressed in the blood and brain in HD patients.
Finally, Dr. Ferrante has been analyzing polytherapies (combined therapeutic trials) associated with multiple molecular mechanisms of disease in neurodegenerative diseases. The concept that single target assays will result in an effective therapeutic may no longer be a sound strategy, as the complexity of different cell interactions and systems may result in adverse events when drug agents are administered in animals and patients. To that end, he has developed compounds with salient pleiotropic properties, as well as the use of mixed agents that we are proposing for use in human clinical trials in neurodegenerative disorders.