Episodic Ataxia

Researchers have discovered that extracts from plants used by the Kwakwaka'wakw First Nations peoples in their traditional botanical medicine practices are able to rescue the function of ion channel proteins carrying mutations that cause human Episodic Ataxia. A University of California, Irvine-led team of researchers have discovered that extracts from plants used by the Kwakwaka'wakw First Nations peoples in their traditional botanical medicine practices are able to rescue the function of ion channel proteins carrying mutations that cause human Episodic Ataxia. The study, "Native American ataxia medicines rescue ataxia-linked mutant potassium channel activity via binding to the voltage sensing domain" was published in June in Nature Communications. "Episodic Ataxia 1 (EA1) is a movement disorder caused by inherited mutations in the human KCNA1 gene, which encodes Kv1.1, a voltage-gated potassium channel essential for normal function of the human nervous system," said Geoffrey W. Abbott, PhD, vice dean of basic science research and professor in the Department of Physiology & Biophysics at the UCI School of Medicine. "We found that extracts of stinging nettle, bladderwrack kelp and Pacific ninebark can all correct function of the mutation- carrying proteins causing a specific form of ataxia." Abbott's research team also found that two compounds contained in these plants, tannic acid and gallic acid, are each able to rescue activity of the EA1-linked mutation-carrying ion channel proteins. "The plant compounds are the first known compounds to rescue the activity of Kv1.1 carrying EA1-linked loss-of-function sequence variants," said Abbott. "Gallic acid in particular is of therapeutic interest because it is already available over the counter as a nutritional supplement and is very well tolerated in toxicity studies." Individuals with ataxia exhibit abnormal gait, slurring, eye movement abnormalities, difficulties with balance and walking, tremors, and disruption of fine motor skills. "These mutations can cause other disorders, including epilepsy, and so there is therapeutic potential for those conditions as well, " said Abbott. "We have discovered that where modern synthetic drug development techniques have failed to produce a drug that directly rescues EA1-linked mutant channel function, traditional botanical medicine developed by North American First Nation peoples has succeeded." Further research is now needed to explore the efficacy of the plant-derived compounds in preclinical and clinical studies. "We have made a mouse model of a relatively severe form of human EA1 so that we can test the efficacy and safety of gallic acid and also whole plant extracts," said Abbott. "If the preclinical studies go well, our goal is to move to clinical trials. Concurrently, we are synthesizing and testing other plant compounds and derivatives to discover other compounds with potential for treating EA1 and related disorders." There are several forms of ataxia, which is an umbrella term describing loss of coordination or balance. Together with Abbott, the research team comprised Drs. Rian Manville, J. Alfredo Freites, Doug Tobias (UC Irvine) and Richard Sidlow (Valley Children's Hospital). This work was supported by the National Institutes of Health and the National Institute of General Medical Sciences.

Findings also reveal new biomarker that may be used in treatment of major depression BURLINGAME, Calif.--(BUSINESS WIRE)-- Magnus Medical, Inc., a medical device company and developer of brain stimulation technology for the treatment of neuropsychiatric disorders, today shared promising results from a clinical trial published in the Proceedings of the National Academy of Sciences indicating that treatment with SAINT™ Neuromodulation reverses abnormal brain signaling by changing the direction of brain signal flow in people with severe depression. Findings also reveal a new biomarker that may be helpful in the diagnosis and treatment of major depressive disorder (MDD). “These findings have the potential to be a game-changer. This strongly supports the role of fMRI resting-state connectivity in our SAINT Neuromodulation System as a method of personalized targeting to treat underlying causes of depression, and suggests that this could be a fundamental biological signature of major depressive disorder,” said Brandon Bentzley, M.D., Ph.D., co-founder and chief scientific officer of Magnus Medical. “Identifying other neural pathways could lead to the discovery of additional biomarkers that characterize other highly debilitating neuropsychiatric disorders.” The study’s senior authors are Marcus E. Raichle, M.D., a Wolff distinguished professor of medicine at Washington University in St. Louis, and Nolan R. Williams, M.D., an associate professor within the Department of Psychiatry and Behavioral Sciences at Stanford Medicine. Researchers conducted the first investigation of the relationship between resting-state fMRI brain activity, major depression, and treatment response to the FDA-cleared SAINT Neuromodulation therapy. Findings show that treatment with SAINT for major depression produces changes in brain signaling by reversing the direction of abnormal brain signals in the bilateral anterior cingulate cortex (ACC)—the region that manages fundamental emotions, which predicts improvement in depression symptoms. Notably, pre-treatment ACC signaling predicts depression severity and the likelihood of a person’s treatment response to SAINT therapy. This reverse signaling may also serve as a biomarker for diagnosing and treating major depressive disorder, the leading cause of disability worldwide.1 Data from 33 patients diagnosed with treatment-resistant major depression, 23 of whom received treatment with SAINT and 10 who received a sham treatment, were compared to 101 healthy individuals. The fMRI data revealed that the anterior insula in healthy people—the region of the brain that supports subjective feelings and sensation—sent signals to the ACC, whereas in 80% of the people with depression, the flow of activity was reversed—the ACC sent signals to the anterior insula. The results also indicate that the higher quantity of abnormal signaling in the ACC is related to the severity of major depression. The SAINT Neuromodulation System uses structural and functional magnetic resonance imaging (MRI) to inform a proprietary algorithm that identifies the optimal anatomic target for focused neurostimulation in people with MDD. This new approach is delivered on an accelerated, five-day timeline with targeting of the stimulation precisely tailored to each person’s brain connectivity. About MDD Major depressive disorder is an episodic disorder that can last months or years.1 According to the World Health Organization, over 280 million people suffer from MDD globally, nearly half of whom have treatment-resistant depression, and far too many experience suicidal thoughts with no rapidly acting treatment options available to them.2 More than 550,0003 adults in the U.S. alone are hospitalized annually for suicidal depression, and the highest peak in suicide attempt4 and completion is immediately after discharge from the hospital, representing an unmet need for rapid and effective treatment in a hospital setting. About Magnus Magnus Medical, Inc., is a privately held medical device company driven to transform lives by restoring mental health. Magnus’ first FDA-cleared product is the SAINT Neuromodulation System, which received FDA Breakthrough Device Designation for its novel, rapid-acting therapy for treatment-resistant depression. The SAINT Neuromodulation System provides a new form of individualized neurostimulation for adults who have failed to achieve satisfactory improvement from prior antidepressant medications. For more information, visit . 1 2 Friedrich MJ. Depression Is the Leading Cause of Disability Around the World. JAMA [Internet] 2017;317(15):1517–1517. Available from: 3 4 View source version on businesswire.com: Contacts Amy Cook Media resources amy@magnusmed.com +1 925.200.2125 Source: Magnus Medical, Inc. View this news release online at: