Current Research Highlights & Stories
Ellen Hess Continues to Break New Ground
No cure for dystonia exists, effective screening and treatment for dystonia helps to lessen the symptoms of muscle spasms, pain, and awkward postures. The goal is to improve the quality of life and functioning of patients with the fewest side effects possible. The Bachmann-Strauss Scientific Advisory Board has announced that the Foundation will continue to fund the Anti-Dystonia Drug Discovery Program, headed by Ellen Hess, PhD, Professor, Department of Pharmacology, Emory University School of Medicine. "My general goal is to understand the pathomechanisms of dystonia by examining the underlying anatomical, physiological and biochemical substrates of the disorder by creating and manipulating mouse models. This strategy allows us to induce or ameliorate motor dysfunction in the context of an intact nervous system revealing potential targets for therapeutics," explained Dr. Hess.
For example, her team is currently using behavioral and cellular pharmacology to understand the cellular mechanisms that give rise to hyperactivity. Continuing her Bachmann-Strauss funded research studies, the objective of Dr. Hess's research is to identify drugs that can either move directly into clinical trial or be put forward for product development by a biotechnological or pharmaceutical company. The drug screening protocol created in the first phase of her research has transitioned to the testing of new compounds to alleviate dystonia symptoms in mice.
Looking ahead, the Anti-Dystonia Drug Discovery Program plans to make drug screening more widely available to facilitate preclinical testing of novel anti-dystonia compounds.
Using explicit criteria and a stringent scientific review process, The Bachmann-Strauss Dystonia & Parkinson Foundation encourages research designed to transform the care and treatment of dystonia and Parkinson’s disease. For 2012, a one-time special Request For Proposal (RFP) focusing on dystonia research was released by the Foundation. Following intense review, the Foundation’s Scientific Advisory Board awarded two interrelated grants. The first grant was awarded to H.A. Jinnah, MD, PhD, Professor, neurology, human genetics and pediatrics, Emory University, and the second to Cristopher Bragg, PhD, Assistant Professor of Neurology, Massachusetts General Hospital. The Board believes these gifted researchers have the potential to develop bold new directions in dystonia treatment.
The goal of Dr. Jinnah’s project – the Dystonia Coalition iPS Resource - is to develop a resource for the collection of skin samples for making fibroblast cultures for dystonia, to create stem cells from these fibroblasts to share with dystonia investigators, and to begin to examine the defects in these cells after they are converted into dopamine neurons.
Using newly developed technology to study neurons of different motor pathways, Dr. Jinnah explained that this technology involves taking a small skin sample from patients with dystonia, growing living fibroblasts from the skin, and then converting the fibroblasts into stem cells for making neurons. These stem cells can be used to generate a variety of different types of neurons. Thus, it becomes possible to have an unlimited quantity of different types of neurons for many different types of studies. As these cells are made from skins samples of dystonia patients, they will contain the genetic defects responsible for the disorder.
Dr. Bragg’s project - Generating Isogenic Dystonia iPS Cell lines with Custom TALE Nucleases - will generate iPSCs to different genetic causes of dystonia by turning normal cells into cells with dystonia mutations with TALE nucleases. Essentially they will be able to create iPSCs to any genetic form of dystonia using TALE technology. Dr. Bragg will also collaborate with the Jinnah laboratory in developing and comparing the different dystonia iPSC models. Directly comparing TALE nuclease -generated iPSC lines to ones generated by reprogramming patient fibroblasts can provide a lot of useful information.
The funds provided by The Bachmann-Strauss Foundation will support efforts to derive iPSCs by different methods. The work will take place over the next two years and will proceed in parallel with Dr. Jinnah’s lab. Dr. Bragg, explained, “Once our labs have derived iPSC models, it will be highly useful for us to coordinate functional analyses of the different models within the same assays, i.e., Dr. Jinnah’s group could potentially differentiate all lines in the same platform and characterize morphologic features, while our group could perform transcriptional profiling on all lines.”
In seeking proposals from extraordinary researchers like Drs. Jinnah and Bragg with the potential for innovative approaches in previously unexplored areas, the Scientific Advisory Board looks for projects that will lead to new tools or new directions for future treatments in dystonia and Parkinson’s disease.
Spasmodic dysphonia is a voice disorder that prevents a person from speaking clearly. Often, when one sounds awful and strains to get words out, people think the person has a terrible cold. This disorder makes telephone conversations an ordeal, and one can easily feel isolated and misunderstood.
Although a rare disorder, spasmodic dysphonia can affect anyone. The first signs of spasmodic dysphonia are found most often in people between 30 and 50 years of age, affecting women more than men.
Neurologically, spasmodic dysphonia is a disorder affecting the voice muscles in the larynx or voice box. When we speak, air from the lungs is pushed between two elastic structures - called vocal folds or vocal cords - with sufficient pressure to cause them to vibrate, producing sound. In spasmodic dysphonia, the muscles inside the vocal folds experience sudden involuntary movements, called spasms, which interfere with the ability of the folds to vibrate and produce the intended sound.
Spasmodic dysphonia causes voice breaks and can give the voice a tight, strained quality. At first, symptoms may be mild and occur only occasionally, but they can worsen and become more frequent over time. Spasmodic dysphonia is a chronic condition that continues throughout a person’s life.
Dr. Naomi Lubarr, a neurologist at The Bachmann-Strauss Dystonia Center of Excellence at Beth Israel Medical Center, explains, “Major concerns for patients with spasmodic dysphonia are the difficulties they have with communication due to the alteration in their voice and speech, and how their impaired voice affects their work life, social life, and family life.”
Continuing, Dr. Lubarr’s advice for coping is to seek the best medical treatment possible, based on each patient’s specific condition and needs. Treatment options include botulinum toxin injections by an experienced ear, nose and throat doctor, and speech therapy. However, paying attention to and treating other aspects of a patient’s overall condition are important, including any associated depression or anxiety.
Dr. Lubarr suggested that limiting voice use when possible, using email or writing notes, exercises as directed by a speech therapist when public speaking is necessary, and expression through other means, such as with a musical instrument, are great too.