The Hershey ALS Clinic and Research - Research

Research

  • Clinic Director: Zachary Simmons, M.D.
  • Basic Science Director: James Connor, Ph.D.

Our research team aims to advance the collective understanding of ALS

Clinical Research

  • 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 Terasemtiv when taken with or without riluzole (also called "Rilutek (R)") and how well it is tolerated in patients with ALS.  Additionally, the effects of Tirasemtiv on the performance of muscle strength, breathing, and muscle endurance will be evaluated.  How much of Terasemtiv gets into the blood-stream and how long it takes the body to get rid of it will also be measured. Patients who enter this study will be randomly assigned to receive either Tirasemtiv or placebo (inactive substance) for 3 months.
  • Mexiletine.  This study aims to find out if mexiletine is safe and if it will have an effect in people with ALS. The study will examine what dose of mexiletine is safe for people with ALS to take without causing too many side effects. In this trial, participants will take either 300mg/day of mexiletine, 900mg/day of mexiletine or placebo (non-active study drug). The study will compare the safety and efficacy of the treatment in these 3 groups.
  • Pure Upper Motor Neuron Disease Registry:  The goal of this project is to develop a Pure Upper Motor Neuron Disease (UMND) Pilot Registry by identifying the location, demographics, and functional status of patients with either early UMND or Primary Lateral Sclerosis (PLS). The project involves a chart review of people with pure UMND who were seen at clinic sites across North America.  The data generated from this project will be crucial to future UMND research.
  • 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. Participants keep a monthly diary of falls and complete phone interviews with our research staff if they experience a fall.
  • Understanding Patient Communications and Treatment Preferences: Based on a review of published literature and opinions of clinical experts, patients and caregivers, we developed the Penn State Hershey ALS Communication and Treatment Preference Assessment.  This is a questionnaire whose purpose is to document completion of legal documents (e.g., advance directive, power of attorney, and living will), express preferences for information, services,  and treatments for ALS, and communicate thoughts about living in the best manner possible with the disease. It is hoped that patient completion of this assessment will enrich the partnership of the clinical team with the patient and family while helping in treatment planning for ALS. We are currently piloting this new assessment in our clinic. We will use the information provided by all ALS patients in this pilot study to modify and improve the assessment so that it may be used routinely in the ALS clinic for all patients during their regular visits.
  • 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.  ALS produces a highly variable clinical course with regard to region of onset of the disease, rate of progression, severity of deficits in various body regions, and is associated frequently with cognitive and behavioral changes which vary from mild to severe. 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.
  • Medical Student Research (MSR): We support the Penn State University College of Medicine MSR projects. The MSR program gives each medical student an opportunity to participate in mentored medical research. Students gain an understanding of the research process, limitations and variability of data, and application of research to clinical practice. Our projects have included: understanding the relationship of quality of life (QOL) and medical inverventions for ALS such as percutaneous endoscopic gastrostomy (PEG) tube and non-invasive ventilation (BiPAP), studying the relationships of negative emotions and QOL, examining patient compliance with ALS clinic recommendations, and researching how bulbar symptoms (speech and swallowing) relate to QOL.
  • Changes in Thinking: In some cases, individuals with ALS develop changes in their thinking and/or behavior. If severe enough, this is classified as a frontotemporal dementia, or FTD. We aim to better understand the cognitive-behavioral changes that sometimes occur in ALS through studying these changes in patients over time.  A product of our early research on the topic, our 20-minute brief exam of cognitive functioning has become a vital tool in our clinic for detecting the subtle changes that sometimes occur in ALS. It is now being used at ALS clinics around the country as part of a multi-center research study.
  • 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.
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: 

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

Basic Science Research

Discovery of a Genetic Risk Factor for ALS: There continues to be close collaboration between our clinical program and the research laboratory of Dr. James Connor. Under his leadership, 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. This gene variant, which occurs in 30% of all ALS patients, was first found in patients visiting our clinic and our findings have now been confirmed in 5 studies around the world including ALS patients in China.  Studies now support that the presence of the H63D HFE gene is a four-fold risk factor for ALS.   In the past year, 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. Furthermore, we will be able to interrogate the mice to determine which disease pathways are activated that accelerates the disease progression which should provide therapeutic targets.  The mouse model will also provide 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 fail in the clinic.

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. As these mechanisms are uncovered, we will understand their importance and ALS and develop therapeutic strategies around that knowledge.
 

Click Here for a List of Recent Publications and Presentations