A team of researchers have discovered that extracts from plants are able to rescue the function of ion channel proteins carrying mutations that cause human Episodic Ataxia.
Individuals with ataxia exhibit abnormal gait, slurring, eye movement abnormalities, difficulties with balance and walking, tremors, and disruption of fine motor skills.
“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. “We found that extracts of stinging nettle, bladderwrack kelp and Pacific ninebark can all correct the 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.”
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.”
Rían W. Manville, J. Alfredo Freites, Richard Sidlow, Douglas J. Tobias, Geoffrey W. Abbott. Native American ataxia medicines rescue ataxia-linked mutant potassium channel activity via binding to the voltage sensing domain. Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-38834-6
University of California – Irvine. “Plant extracts used by indigenous people hold promise in treatment of ataxia: The plants contain the first-known compounds to reverse dysfunction caused by gene mutations underlying specific neuromuscular and coordination problems.” ScienceDaily. ScienceDaily, 21 June 2023. <www.sciencedaily.com/releases/2023/06/230621164651.htm>.
Photo by: Jackie Dilorenzo