Penn State Hershey ALS Clinic and Research Center

Research

We strongly believe that research into the causes of ALS and other motor neuron disease will eventually be the key to more effective treatments and to a cure.  We also believe that research can lead to a better understanding of factors contributing to quality of life of individuals with ALS and their families.

With funding from the ALS Association Greater Philadelphia Chapter, the Campbell Fund for ALS Research, Department of Defense, and many other individuals and groups, the Penn State Milton S. Hershey ALS Clinic and Research Center carries out studies at several levels:

  1. Clinical trials of medications that show promise for treating ALS.
  2. Clinical research to improve care and support of patients and their caregivers.
  3. Basic science research involving genetics, biomarkers, oxidative stress, iron metabolism, and other factors believed to be involved in the pathogenesis of ALS.

 

Clinical Research Faculty

Basic Science Research Faculty

Zachary Simmons, MD

Professor, Departments of Neurology and Humanities

Director, Neuromuscular Program and ALS Center

James Connor, PhD

University Distinguished Professor

Vice-Chair, Department of Neurosurgery

Stephen Schiff, MD, PhD

Brush Chair Professor of Engineering

Professor, Department of Neurosurgery

James Broach, PhD

Chairman, Biochemistry and Molecular

Biology Director, Institute for Personalized Medicine

Stephanie Felgoise, PhD

Professor and Vice-Chair, Department of Psychology

Philadelphia College of Osteopathic Medicine

Glen Gerhard, MD

Professor, Department of Biochemistry and Molecular Biology

Institute for Personalized Medicine

Susan Walsh, RN, MSN, ACNS-BC

Regional Nurse Manager

ALS Association Greater Philadelphia Chapter

 

Beth Stephens, MA, CCRC

Neuromuscular Program Manager

 

 

If you are interested in learning about our research, please contact our research manager, Beth Stephens at 717-531-0003, ext. 283395. 

Clinical Research

H.P. Acthar Gel (Acthar) (also known as adrenocorticotropic hormone, ACTH, ACTH gel and corticotropin) is a formulation of hormones that causes increased production and release of other hormones called corticosteroids (also known as glucocorticoids) known to suppress the immune system.  Acthar is approved by the U.S. Food and Drug Administration for the treatment of a number of disorders including multiple sclerosis, infantile spasms, dermatomyositis (DM) and polymyositis (PM). Investigators associated with the trial will evaluate the safety and tolerability of four different dosing regimens of Acthar to help inform dose selection of future studies of the drug in ALS.

Tirasemtiv (CK-2017357) is being investigated as a potential new therapy for the improvement of muscle weakness and muscle fatigue in patients with ALS. The purpose of this research study is to evaluate the safety and effectiveness of Tirasemtiv and how well it is tolerated in patients with ALS. 

Mexiletine, a sodium channel blocker that has been FDA-approved for the treatment of cardiac arrhythmias and neuropathic pain in diabetic polyneuropathy, has been shown to be neuroprotective, largely by blocking excitotoxicity. This study aims to find out if mexiletine is safe and tolerable and if it will have an effect in people with ALS.

Brain-Computer Interface Technology: Brain-computer interface (BCI) devices have the potential to enhance the quality of life for those living with ALS, and can aid in basic forms of motor control and communication.  In collaboration with Dr. Steven Schiff, our research aims to show how the success of BCI deployment is complicated by the high level of disease heterogeneity, and how we can use engineering principles to adapt our systems to optimize BCI use for each user.

Longitudinal Outcomes Research:  A new strength measurement device called Accurate Test of Limb Isometric Strength (ATLIS) was developed to precisely and conveniently measure static limb strength in patients with ALS. We will compare ATLIS data with data from two commonly used ALS outcomes measures, the ALS Functional Rating Scale-Revised (ALSFRS-R) and slow vital capacity (SVC) in a prospective, longitudinal study. All three outcome measures will be performed on subjects collected preferably at clinic visits during the study period.

Understanding Falls: We are investigating the characteristics and circumstances of falls in people diagnosed with ALS in order to identify risk factors and prevent injuries from falls.

Understanding Pain in ALS: ALS has generally been considered a painless disorder, but recent studies have shown that pain is a frequently underestimated and under-reported symptom in ALS. We are conducting a study of pain experienced by ALS patients in Pennsylvania to better understand the nature of the pain and how it is currently treated. We will simultaneously survey ALS physicians in the U.S. and Canada on their experiences with pain management in the ALS population. From this study, we hope to contribute to the development of better pain management for people living with ALS.

Quality of Life: We have a longstanding interest in quality of life (QOL) in patients with ALS. Our group has developed a QOL questionnaire specific for those with ALS, the ALS-Specific Quality of Life Instrument - Revised, or ALSSQOL-R.  The ALS-Specific Quality of Life-Revised (ALSSQOL-R) is available free of charge to those wishing to use it. (View and download the ALSSQOL-R Manual here). We welcome collaboration from other ALS centers for projects using this instrument.  Those interested in such collaboration should contact Dr. Zachary Simmons at zsimmons@psu.edu. We are currently working with investigators in US centers and International centers to understand QOL in patients with different cultural and ethnic backgrounds. We have recently constructed a short form of the tool (ALSSQOL-SF) which includes 18 items. We are in the process of validating the ALSSQOL-SF in a multicenter study.

Turning Research into Practice: Evidence-Based Practice is a method of providing clinical care to patients, by systematically incorporating solid research evidence with clinician expertise. This process has inspired several collaborative teams, made up of clinicians and researchers alike. Each group focuses on a particular aspect of patient care, in order to better meet the needs of our patients. Topics include: 

Basic Science Research

Discovery of a Genetic Risk Factor for ALS:  Under the leadership of Dr. James Connor, a potential genetic risk factor for ALS has been identified. Termed the H63D HFE genetic variant, this is a variation of the hemochromatosis gene, a gene involved in iron metabolism, the immune system, and inflammatory responses. Studies now support that the presence of the H63D HFE gene is a four-fold risk factor for ALS.  

Developing Innovative Mouse Models of ALS: We have successfully developed a mouse model that expresses the HFE risk factor gene and mated that mouse line with the established ALS mouse model. The resulting mice have a faster and more aggressive disease. This is an exciting breakthrough and will provide opportunities to understand how the risk factor we identified impacts the disease.  This also provides a new model in which to test therapeutic strategies under consideration for ALS and hopefully improve the currently poor success rate for drugs that tested well in animal models but failed in human trials.

Understanding Cellular Stress and ALS: Studies to understand the relationship between H63D and cellular stress and between H63D and two other mutations known to be associated with ALS - TDP-43 and SOD1 - are in progress. Human cells that carry the H63D mutation have elevated levels of stress and mitochondrial dysfunction and alterations in glutamate metabolism and increased TDP-43 that are thought to contribute to ALS. These models will help us to understand the impact of the mutations on cell function and how the mutations combine to cause cell death, permitting the development of therapeutic strategies around that knowledge.

Biomarker Research: We have made progress with a novel biomarker-panel based approach to model ALS disease prognosis. We found that several important biomarkers involved in inflammation, iron metabolism, and immune responses may predict ALS disease course. Because current methods to predict prognosis are limited, these results have direct impact on clinical management and trials of novel therapies. We are currently establishing a repository of samples to be used for biomarker research.

Personalized Medicine: Since the creation of Penn State Hershey's new Institute for Personalized Medicine, this game-changing medical model is driving opportunities for greater collaborations across the institution to advance medical science.  In collaboration with Drs. James Broach and Glenn Gerhard, and with patient and family member consent, blood and saliva samples will be taken and used to conduct highly sophisticated genetic sequencing.  The process will identify known or new genetic mutations that are associated with ALS. 

Click Here for a List of Recent Publications and Presentations