Medication May Lessen Dystonia with Fewer Side Effects than Existing Drugs
The Dystonia Medical Research Foundation (DMRF) and Cure Dystonia Now (CDN) are collaborating to co-support a research investigation that may lead to a new drug for dystonia, the third most common movement disorder following essential tremor and Parkinson’s disease. The medications most frequently prescribed to treat this debilitating disease are ironically those with some of the highest incidence of intolerable side effects, which limit their use. A team of American and European investigators is exploring whether a drug called AZD1446 could potentially provide relief for dystonia patients without the unintended effects frequently caused by existing pharmacological therapies.
The investigation is led by David Standaert, MD, PhD, Professor and Neurology Chair at University of Alabama and includes Antonio Pisani, MD, PhD, Associate Professor of Neurology at University of Rome Tor Vergata.
Art Kessler, President of the DMRF, explains: “This project addresses two important issues for the dystonia community: We need additional treatment options and we need to find new ways to offer treatment with minimal side effects. This project provides an important opportunity to investigate a possible new medication for dystonia while pursuing a better quality of life for patients.” Kessler developed an especially debilitating childhood onset form of dystonia at age eight and knows firsthand the challenges inherent in treating the disease.
Marc Miller, Director and Co-President of CDN states, “Our priority is to work with the brightest and most motivated doctors and scientists, and our goal is to discover new treatments. This project is an exciting opportunity to do both.” Two generations of the Miller family are affected by dystonia.
Dystonia is a neurological disorder that causes skeletal muscles to contract or spasm involuntarily, resulting in twisting, repetitive movements and/or sustained, abnormal postures. A person who is affected by dystonia struggles against the movements of his/her own body to walk, sit or rest comfortably, eat, write, and/or speak. It may be impossible to sit still. Treatment typically requires a combination of approaches including oral medications, botulinum neurotoxin injections, surgical interventions, and supportive therapies such as physical therapy. In some people, a class of drugs called anticholinergics may replace or compound the physical symptoms with equally disabling cognitive effects such as drowsiness, hallucinations, and memory difficulties. Striking a balance between controlling the dystonia and preserving the ability to function in daily life is a challenge for physicians and patients alike.
Dystonia results from improper signals in the nervous system that instruct muscles to contract excessively. Experts do not yet fully understand the neurological mechanism that causes the abnormal muscle contractions, but the origins appear to stem from an imbalance of neurotransmitters in the brain and changes in brain cell synapses. Standaert and team are using a genetically engineered mouse with abnormal neuronal signaling to examine whether AZD1446 can correct the abnormal signaling and restore the balance of neurotransmitters. In separate studies, the drug has been examined for use in treating attention deficit/hyperactivity disorder and Alzheimer’s disease.
Cure Dystonia Now is a 501(c)(3) non-profit organization working with researchers on cutting edge treatments and ultimately a cure for dystonia. Learn more about Cure Dystonia Now at www.curedystonianow.org.
The Dystonia Medical Research Foundation is a 501(c)(3) non-profit organization dedicated to advancing research for improved dystonia treatments and ultimately a cure, promoting awareness, and supporting the well-being of affected individuals and families. The DMRF can be reached at 800-377-3978 or www.dystonia-foundation.org.
New study sheds light on cost of medications and perception of how well they work
A new study says that the cost of a medication may play a very important role in a patient’s perception of whether it works.
People’s perceptions of the cost of a drug may affect how much they benefit from the drug — even when they are receiving only a placebo. The finding, from a new study of people with Parkinson’s disease led by Alberto J. Espay, M.D., of the University of Cincinnati, and Jerzy P. Szaflarski, M.D., Ph.D., of the University of Alabama at Birmingham, is published in the Jan. 28, online issue of Neurology, the medical journal of the American Academy of Neurology.
“Patients’ expectations play an important role in the effectiveness of their treatments, and the placebo effect has been well-documented, especially in people with Parkinson’s disease,” said Espay, study author. “We wanted to see if the people’s perceptions of the cost of the drug they received would affect the placebo response.”
For the study, 12 people with Parkinson’s disease were told that they would receive shots of two formulations of the same drug, with the second shot given after the benefits of the first shot had subsided. They were told that the formulations were believed to be of similar effectiveness, but that they differed in manufacturing cost — $100 per dose versus $1,500 per dose. Participants were told that the study was intended to prove that the drugs, while priced differently, were equally effective.
In reality, the participants received only a saline solution (placebo) for both injections, but were told they were receiving either the “cheap” or “expensive” drug first. Before and after each shot, participants took several tests to measure their motor skills and also had brain scans to measure brain activity.
“When patients received the ‘expensive’ drug first, their motor skills improved by 28 percent compared to when they received the ‘cheap’ drug, which was twice as much,” said Szaflarski, senior author of the study while on the faculty at the University of Cincinnati. He now is director of the Division of Epilepsy in the Department of Neurology at the University of Alabama at Birmingham. “On one test of motor skills, people’s scores improved from 29 to 22 points when taking the ‘expensive’ drug first, but improved by only 3 points when taking the ‘cheap’ drug. In addition, the ‘expensive’ drug decreased activation in the brain similar to that of the Parkinson’s drug levodopa, while the ‘cheap’ drug increased activation in the brain,” indicating differential responses to the medication cost.
“If we can find strategies to harness the placebo response to enhance the benefits of treatments, we could potentially maximize the benefit of treatment while reducing the dosage of drugs needed and possibly reducing side-effects,” Espay said.
Espay says that the placebo response may be stronger in people with Parkinson’s because the disease decreases the amount of dopamine in the brain and the placebo effect is known to increase the release of brain dopamine. Dopamine affects movement; but it also affects anticipation, motivation and response to new things. “People who receive the shots thinking they received a drug may have an ‘expectation of reward’ response, which is associated with the release of dopamine similar to the response to the reward itself,” he said.
The study received extra scrutiny from the university’s review board before it began, since it involved intentional deception of the participants. The review board found that the study complied with federal research regulations that allow waiver of the informed consent requirement, and that the deception would have no adverse effects on the rights or welfare of the participants.
After the study, the participants were told about the true nature of the study. “Eight of the participants said they did have greater expectations of the ‘expensive’ drug and were amazed at the extent of the difference brought about by their expectations,” Espay said. “Interestingly, the other four participants said they had no expectation of greater benefits of the more expensive drug, and they also showed little overall changes.”
The study was supported by the Davis Phinney Foundation for Parkinson’s. To learn more about Parkinson’s disease, please visit www.aan.com/patients.
By Bob Shephard
UAB Huntington's Disease Clinic
In January 2011, the UAB Department of Neurology opened a new multidisciplinary Huntington’s Disease Clinic. Our clinic has been named by the Huntington’s Disease Society of America (HDSA) as one of only 22 Huntington’s Disease Centers of Excellence in the United States. Below are highlights of this initiative, including a brief bio of our faculty and staff. Your care is important to us, and we hope that you will find this enhancement of our Huntington’s Disease clinic encouraging.
MEET OUR STAFF
| Victor W. Sung, MD
David G. Standaert, MD, PhDDavid G. Standaert, MD, PhD:Dr. Standaert is the Chair of the UAB Department of Neurology, the John N. Whitaker Chair of Neurology, and was recruited from Harvard University in 2006. He received an MD and PhD from Washington University in St. Louis in 1988 and completed residency training at the University of Pennsylvania. At Harvard, Dr. Standaert was involved in research and clinical care for Huntington’s. In addition to being Associate Director of the Huntington’s Disease Clinic, he also serves as Director of the Center for Neurodegeneration and Experimental Therapeutics (CNET) and Director of the Division of Movement Disorders at UAB.
| Jenna Smith, RN, BSN
Your UAB Huntington’s Disease Clinic team
(Left to Right, Leslie Harper, Dr. Sung, Laura Ellis, Dr. Standaert, Fallon Brewer, Jenna Smith, Cindy Sargent, Amy Holmes) will work closely together to provide multi-disciplinary care to address all your needs at each visit.
Laura Ellis, MS, LPT is the Physical Therapist for the clinic and will provide PT evaluation and individualized treatment plans for balance and walking during each visit.
Cindy Sargent,OTR/L is the Occupational Therapist for the clinic and will provide OT evaluation and individualized treatment plans for coordination and tasks involving daily basic function during each visit.
Leslie Harper, MS, CCC-SLP is the Speech Therapist for the clinic and will provide speech and language evaluation and individualized treatment plans for speech and swallowing during each visit.
Amy Holmes, LGSW is the Social Worker for the clinic and is familiar with several resources available and can help with social and psychosocial needs.
Fallon Brewer, MS, CGC is the Certified Genetic Counselor and is very involved in the clinic to address any questions related to genetic testing.
We know Huntington’s disease not only affects you as an individual but also your family. Each member of our team is specialty trained to provide the unique care required for Huntington’s Disease patients. Our goal is to provide the best comprehensive care available to patients while also providing support for your family and loved ones. We look forward to serving you, and please feel free to contact us if there is anything we can do for you.
Jenna Smith, RN, BSN
UAB researcher receives grant to study decision-making abilities in cancer patients
A University of Alabama at Birmingham researcher has received an American Cancer Society Mentored Research Scholars grant to study long-term decision-making abilities in patients with advanced cancer.Kristen Triebel, Psy.D., assistant professor of neurology and director of the Neuropsychology Fellowship Training Program in the UAB Department of Neurology, has been awarded a five-year, $728,000 grant for her work titled “Decisional Capacity Evaluation in Metastatic Brain Cancer.”
Metastasis, or the spread of a cancer from one organ or disease site to another,to the brain occurs in 25 percent of all individuals with cancer. Due to cognitive impairment, emotional distress and other changes occurring as a result of their severe illness, individuals with brain metastases frequently have reduced capacity to make well-informed decisions about their medical treatment. These decisions may include deciding among focused or whole-brain radiation, surgery, chemotherapy or palliative care, or whether to pursue experimental treatment. Surprisingly, decisional capacity is not routinely assessed in this patient population prior to patients’ consenting to treatment.
The ACS grant allows Triebel to critically study patients with advanced cancer, including lung and breast cancer that has metastasized to the brain, and pancreatic cancer. She also will examine issues in these patients’ treatments, cognitive function and quality of life.
“Patients with advanced cancer are seriously ill and have to make a lot of important medical decisions,” said Triebel, an associate scientist in the Cancer Control and Population Sciences program at the UAB Comprehensive Cancer Center.“We are looking to see whether our initial findings from metastatic cancer patients can generalize to other cancer populations who have comparable levels of illness — even those who don’t get tumors that spread to the brain.”
According to Triebel, the goal is to be able to improve decision-making capacity. “We hope this research leads to better understanding of patients at risk, so we can advise on best practices for assessment and interventions to support patients in this capacity, ultimately improving their quality of life.”
Triebel, who received a Center for Clinical and Translational Sciencegrant in 2012, leveraged that research into this five-year grant from ACS. “This award provides opportunities for me to grow a research program by fostering collaboration with other cancer investigators. And it also allows me to pursue other career-development opportunities.”
At a time when funding opportunities are difficult to attain, Triebel is an example of what researchers need to do to secure additional funding that has the potential to change the future of cancer treatment and care. She emphasizes the protected time and money to conduct the research that the CCTS grant allowed, as well as “access to successful researchers who taught me how to conduct research and write grants,” she said. “That grant was great, providing two years of support that allowed me to do the research, which in turn helped me secure this larger ACS grant.”
Ultimately this work comes down to the patients. “Certainly, this study will address the knowledge gap by investigating medical decision-making capacity in patients; but the great potential is to improve clinical practice and decision-making for these populations,” said Triebel.
By: Beena Thannickal