Research
Current Basic and Translational Research
Two of Dr. Ferrante’s research interests in ALS are characterizing biomarkers of ALS and in drug development to translate therapeutic strategies to patients with ALS. Dr. Ferrante has funding that supports biomarker analysis. Biomarkers are urgently needed for diagnosis, following disease progression, and for their utility in measuring outcome measures using potential disease-modifying therapies that are being developed and evaluated in clinical trials, especially at the early stages of disease. While the development of early biomarkers is of great importance, as these may improve the power of clinical trails, it is likely that more than one biomarker will be needed for early diagnosis and similarly for evaluation of disease progression for therapeutic trials. Thespecific aims of this work are designed to identify and follow biomarkers that correspond to disease activity, disease progression, and disease modification in ALS mouse models in parallel with human ALS patients. The utility and validity of peripheral biomarkers (blood and urine) are critically vital in facilitating lead screening in mouse models and in human therapeutic clinical trials. The project analyzes and compares peripheral (blood and urine sample) to CNS biomarker profiles (brain tissue and csf) in ALS mice throughout presymptomatic and symptomatic disease and compares these findings to human ALS patients. These studies have demonstrated that peripheral biomarker profiles reflect changes in the CNS. By using ALS mice, we can examine complementary processes in the brain and periphery with much greater precision and much greater control of post-mortem and other technical factors. We have sufficient correspondence so far between ALS mouse models and ALS subjects to provide confidence that the animal studies will greatly facilitate the overall program. The current technologies allow for the measurement of multiple known and hypothesized biomarkers within the same individual and across comparable groups of humanpatients and animal models with ALS. This information will help to create adata set of multiple markers that can be used to develop a unique biochemical signature relating to ALS subjects that will provide a powerful means to assess therapeutic treatments in ALS patients and predict the potential magnitude of benefits in these patients.
In addition, Dr. Ferrante also has funding to develop novel drug therapies for ALS patients for use in human clinical trials. This work investigates protein aggregation inhibition as a potential therapeutic strategy for ameliorating disease progression in ALS. Dr. Ferrante and his colleagues at Northwestern University and Boston perform high throughput screens to identify compounds that protect cells against the toxic effects of mutant superoxide dismutase (SOD1) aggregation. SOD mutations are the cause of familial forms of ALS. They have identified three lead chemotypes that protect cells from aggregated mutant SOD1. Dr. Ferrante found that CMB-021805, a PYT analog, when administered to G93A ALS mice, improved survival and extended the life of the mice by 26%. Pathological findings in untreated G93A mice, including gross spinal cord atrophy and neuronal loss in the ventral horns from the lumbar spinal cord, were significantly reduced by CMB-021805, as compared to untreated ALS mice. In addition, when mice were treated with CMB-021805 at 10 mg/kg twice daily, survival was extended by approximately 31% in the G93A mice, as compared to untreated ALS mice. These findings are better than any current drug trial in ALS mice. He and his colleagues are developing this compound for use in clinical trials in ALS patients. While additional experiments are needed, the findings described above may lead to a better understanding of the disease mechanisms that initiate ALS, as well as identifying targets for potential biomarkers and new therapies to combat ALS.
Current Clinical Research Projects
Optimizing Nasal Ventilation for People with ALS
In this research study, we are comparing standard monitoring of nasal ventilation use to an enhanced approach. In the enhanced approach, patients and caregivers are given information on how effectively they are using devices. The study is no longer recruiting and is in the data analysis phase. Read More >
A Clinical Trial of Dexpramipexole in ALS (EMPOWER)
In this research study, subjects are receiving oral dexpramipexole or a placebo for 12-18 months in order to determine if the drug is effective and safe in ALS. The study is closed to enrollment. Read more >
Clinical Trial of Ceftriaxone in Subjects with Amyotrophic Lateral Sclerosis
Research subjects for the ‘Clinical Trial of Ceftriaxone Subjects with ALS’ are being recruited at the University of Pittsburgh Medical Center. Five hundred research participants with Amyotrophic Lateral Sclerosis (ALS) are being recruited for this double-blind study of Ceftriaxone. Read More >
Clinical Study of Cognitive Dysfunction in Subjects with Amyotrophic Lateral Sclerosis
Research subjects for the study ‘Cognitive Dysfunction in ALS’ are being recruited at the University of Pittsburgh Medical Center. Six research participants with Amyotrophic Lateral Sclerosis (ALS) are being recruited for this pilot study combining neuropsychological testing and neuroimaging studies, including MRI of the brain and MEG (magnetoencephalography). Read More >
Western PA Study
Epidemiological Descriptive Analysis of a Case Series of ALS Patients from 2008-2009 in Six Counties of Western Pennsylvania Read More >
