December 27, 2012
Terry Heiman-Patterson, MD, is Chief of neuromuscular disorders at Drexel University College of Medicine, Medical Director of the MDA/ALS Center of Hope at Drexel University College of Medicine, Co-Founder and President of the Board of the ALS Hope Foundation, and a NEALS Executive Committee Member.
Dr. Terry Heiman-Patterson recalls clearly the first individual she diagnosed with ALS as a junior neurology faculty member. It was this encounter which led her to focus her career on improving quality of life for people with ALS and conducting clinical research that might eventually lead to a cure.
Today, apart from her diligent work as a Chair on the NEALS Biorepository Committee, Dr. Heiman-Patterson and her team conduct/participate in both pre-clinical and clinical studies. Their pre-clinical research focuses on transgenic mouse models. Their clinical studies include investigational treatments as well as quality of life research.
Dr. Heiman-Patterson and her laboratory team are actively exploring several pre-clinical interests. Two exciting projects endeavor to find the genes that influence phenotype (how severe the disease is) and to learn more about the potential role of environmental toxicity. Dr. Heiman-Patterson and her team previously noted that there was a significant variation in the life span of transgenic mice with the SOD1 mutation. They theorized this might be because there are genes carried by some of the mice that moderated the disease process or made it more severe. Through various linkage studies (which link how long a mouse lives and when its symptoms begin to different chromosomal regions), Dr. Heiman-Patterson and her team have narrowed the search to approximately thirty four different genes that could potentially be responsible for modulating the disease in SOD1 mouse populations. “If we are able to identify the gene, this can provide information on pathways important to motor neuron disease that may even be targets for new therapies,” she states.
Alternatively, the cause of the difference in severity may not be an actual gene but alterations in the genetic sequence that contains information on how the genes are translated or in regions that normally remain untranslated. Dr. Heiman-Patterson explains, “We are trying to find out what that modifier is, and that’s what our funded work is about.” She adds, enthusiastically, “We are very excited since it may give us a new direction to pursue for treatment.”
Once Dr. Heiman-Patterson and her team identify the source of genetic variation in the mouse model, they will translate their research to humans with ALS. Their goal is to “identify a predisposing [genetic] disease modifier and [see] if that will provide a target pathway that we can use to develop therapies.” Dr. Heiman-Patterson’s lab has developed a partnership with researchers at the Jackson Lab, a leading nonprofit genetics research organization, who independently identified the same region as modifying ALS in SOD1 mice. “The Jackson Lab and our lab have been collaborating because we feel very strongly that together we will do much better,” Dr. Heiman-Patterson explains.
Mouse models are also used to piece together answers to questions about toxic exposure. Does increased exposure to certain chemicals, at a level below the EPA rating, lead to a change in the way phenotypes are expressed in the mice? Does disease onset occur sooner? Does it occur in animals that would not normally develop symptoms of ALS? Dr. Heiman-Patterson created a transgenic mouse model that expresses a “low level” of the disease; these mice carry 4 copies of the human-mutated gene associated with ALS, as opposed to the 24 copies carried by typical SOD1 model populations. If this “low level” mouse is exposed to a certain toxin, will the toxin accelerate or initiate the disease process? Dr. Heiman Patterson explained that, “Many patients are worried about exposure; did it cause my ALS? This is one way to get at if these toxins actually can increase motor neuron damage. So if a patient’s motor neurons are not great and they get exposed to toxin X, will that trigger their disease?” If these studies show symptom acceleration in exposed mice, it would suggest that toxins may play a role in the development and progress of ALS.
Quality of Life/Device Studies
Outside the laboratory, Dr. Heiman-Patterson is also striving to improve the lives of people with ALS now by examining strategies to help PALS live fuller and more independent lives. Assistive technology “can really make a difference in promoting independence and control and in making a difference in the lives of people who have to live with this disease everyday,” she compassionately explains.
Such device trials study how available technologies, as well as new, emerging technologies, can help PALS control their environments. “If we could provide systems where you could turn on a light, change the channel with the remote, and open an email, it would open up the horizon so you could still feel like you had a good quality of life,” explains Dr. Heiman-Patterson. The EEG-based Brain-Computer Interface (BCI) is a tool to help PALS without movement interact with their environments through environmental control software. BCI is still in development, but Dr. Heiman-Patterson is at the forefront of making this technology work for PALS. She has also ensured that current technology is available for PALS who have been admitted to Drexel hospital rooms. For instance, she prompted the hospital to install “eye gaze switches, hoyer lifts over the hospital beds, and home-like environments for caregivers who may be staying with the patient and are using this technology to make life better.” She continues, “With the help of a student, we have even developed some technology inexpensively that will be used for [environmental] control, and we are hoping to develop these [devices] and get them used and distributed in our clinic.”
The implications of quality of life studies go beyond independence and control. “Device research is two-fold,” Dr. Heiman-Patterson emphasizes. These techniques have a secondary purpose – possibly providing EEG or other biologically derived information that can be used as biomarkers. Both the iBrain (which responds to PALS’ EEG brain waves) and Functional Near Infrared (fNIR) Spectroscopy (which detects oxygen utilization), have the potential to provide not only a switch that can be used to indicate a choice but also a biomarker that reflects either intent or disease changes over time. In the iBrain, a single electrode recording is analyzed with a special algorithm (Spears) developed by Neurovigil, that can detect intent and may have characteristics that differ between normal and disease subjects. Therefore, not only might this device be used to indicate choice or intent but also may provide a biomarker to follow during treatment in trials or for diagnosis. In the case of the fNIR, rather than brain waves providing the signals of intent and potential biomarkers, it is the change of oxidation in hemoglobin in the front of the brain that will provide the information. In fact, fNIR may eventually be capable of examining metabolic work of cognitive tasks and differences in ALS and controls. In both cases, if longitudinal changes over the course of the illness are detected, then these techniques also will provide markers of disease progression that can be monitored during treatment and potentially to help in diagnosis.
Dr. Heiman-Patterson’s ultimate goal is to nurture a sense of community and teamwork between funders, ALS clinicians, scientists, physicians, and patients. Although they come at the problem from many different angles, all of these parties share the same interest: to improve the lives of people with ALS. Dr. Heiman-Patterson worries that these individuals sometimes lose sight of what can be gained through open communication and collaboration. She insists that, with time, dedication, creative thinking, and teamwork, we will find treatments and a cure for ALS—maybe even sooner than we think. What people do not always recognize, she says, is the need to “make it about collaboration, cordiality, and moving the field forward,” and not about individual achievements. The focus should always be “the patient and nothing else,” she insists. Dr. Heiman-Patterson has found inspiration and strength in her patients, who remain her number-one priority.