The MDA/ALS Center of Hope provides an important setting for research towards understanding, treating, and curing ALS. That is why the ALS Hope Foundation supports an extensive clinical research program at the Center of Hope. Without research, there would be no progress in our fight against ALS. Clinical Research is a broad term, encompassing clinical trials (studies on the effect of a medicine on the disease or its symptoms) and clinical research that examines other aspects of the illness, such as assistive technology or quality of life. Clinical research at the Center complements our basic research program, in the hope that promising therapeutics identified at the lab bench can be tested for efficacy in the clinic. For more information, please contact our Research Coordinator, Lindsey Colman, at lindsey.colman@tuhs.temple.edu or 215-707-7845.

Clinical Research: Ongoing Projects

Tirasemtiv Clinical Trial

We are participating in the Phase III clinical trial of the experimental drug called Tirasemtiv to examine whether this drug improves lung function and muscle strength in people with ALS. Previous studies have demonstrated that Tirasemtiv is safe and well-tolerated when administered over 14 days. This drug improved muscle function in SOD1(G93A) mice, the animal model of ALS. The major side effect was dizziness. See the official press release from Cytokinetics here.

Diaphragmatic Pacing

As ALS progresses, breathing can become difficult due to weakening of the breathing muscles. The Synapse Biomedical NeuRx® Diaphragm Pacing System™ (DPS) is a four channel, implanted percutaneous diaphragm muscle stimulation system that is used to assist in diaphragm functioning. Since DPS has not been rigorously evaluated in ALS populations, a clinical trial has been designed to scientifically determine its effectiveness in improving diaphragm function and survival in ALS patients. This trial remains open but is not currently enrolling.

Cognitive-Behavioral Study

While ALS primarily affects the motor system, up to 40% of PALS have cognitive impairment with predominantly executive dysfunction, while approximately 20% of PALS show behavioral changes, predominantly apathy and disinhibition. These cognitive and behavioral changes add significantly to the burden and distress of caregivers who now have to face the challenges of managing behavioral changes in addition to physical disability. Given this increasing burden, there is a critical need for validated interventions that can help the caregiver manage these behaviors. However, there is no standard and/or validated intervention currently available, nor has there been investigation directed at helping caregivers to manage these behavioral changes in ALS. The overall goal of our study is to characterize the relationship of caregiver burden to cognitive and behavioral impairment in ALS and to develop and perform a feasibility study of a pilot individualized intervention as a way to reduce caregiver burden. Ultimately, this study will provide the necessary background to develop, inform, and guide future targeted and larger scale interventions directed to both PALS and caregivers.

fNIR Optical Imaging 

Figure 1

Figure 1

The overall goal of this project is to determine if there are hemodynamic changes detected by Functional Near Infrared (fNIR) Spectroscopy that differ in PALS and controls and whether these changes correlate with cognitive changes assessed with neuropsychological tests in ALS. While the traditional teaching has been that cognition in ALS is intact, recent evidence suggests behavioral and memory deficits from frontal lobe brain involvement in a sizable number of PALS.  Functional Near Infrared (fNIR) Spectroscopy is a safe, non-invasive, and portable optical neuroimaging technology that can be used to monitor hemodynamic changes that occur in the brain, such as blood oxygenation and blood volume, during select cognitive tasks. The system is composed of three modules: a flexible headpiece (sensor pad), which holds light sources and detectors; a control box for hardware management; and a computer that captures data (see Figure 1). The safe, portable, and cost-effective nature of fNIR suggests that this technology is an ideal candidate for monitoring cognitive activity with concomitant hemodynamic changes not only in the laboratory but also in the clinic.

In our studies, we will examine whether there are hemodynamic differences between PALS and controls during thinking tasks.We will also compare PALS with and without cognitive changes on formal neuropsychology tests. If corresponding changes can be identified in PALS, this will set the foundation for longitudinal studies to determine if fNIR can provide a biomarker to be followed during clinical studies, as well as whether it can help identify and track ALS subjects at risk for cognitive involvement at an earlier stage of illness than traditional neuropsychological assessments. 

iBrain: Communication in ALS 

The objective of this project is to examine whether a single channel of electroencephalogram (EEG) data, recorded by Neurovigil’s iBrain™ device can be analyzed to identify brain waves that will serve as neurological biomarkers of human intent. This would allow us to use these biomarkers to enable a wide range of PALS to communicate throughout all stages of disease progression. Preliminary results from Neurovigil’s signal analysis of data collected on Professor Steven Hawking, revealed high frequency/low spectral power signals when he attempted to move. Distinct signals were demonstrated and appeared specific to attempted or imagined movements. We plan to validate these preliminary findings in a larger group of ALS subjects. If successful, these signals indicating the subject's intent could be used to link brain activity with a library of words and convert them into speech, thus providing people living with ALS communication tools more dependent on the brain than on the body. We are partnering with Neurovigil to perform these studies.

EEG-Based Brain-Computer Interface

By using EEG (brain wave) signals from the scalp to create a signal, the Brain-Computer Interface (BCI) allows people to make selections from a computer screen. This study is intended to evaluate both the complexity of the system and the degree to which each participant will be able to communicate using BCI. Trials will consist of asking the subject to follow a series of simple instructions and to complete certain tasks while using the BCI in our clinic or offices. We are also working to simplify the system as a prelude to home based use.

Tissue Donation

In a disease like ALS in which the cause is unknown, no animal models of ALS can substitute for understanding how it affects humans. We are currently collecting blood, urine, cerebrospinal fluid, and autopsy materials from people with ALS and other motor neuron diseases to look for clues in the human tissue. All samples are tied to de-identified clinical information in a database to help maximize the usefulness of this precious resource. The anonymous database includes demographic information, environmental exposures, and medical history. This will increase availability of human tissue for research with pertinent corresponding clinical information.

GI Dysmotility

Studies have shown delayed gastric emptying may be associated with ALS, possibly due to involvement of the autonomic nervous system. This may be the cause of the abdominal discomfort and constipation commonly observed in ALS. Our study examines the small bowel transit time in people with ALS and in control subjects in an effort to gain further insight into the extent and severity of GI dysmotility in PALS. Companion studies are also underway in autopsied material that examine the pathology underlying the delay in GI motility.