Researchers from the University of California have discovered that extracts from plants used by the Kwakwaka'wakw First Nations peoples in the Pacific Northwest can potentially treat type 1 episodic ataxia by rescuing the function of ion channel proteins.
Episodic ataxia type 1 is an autosomal dominant inherited form caused by genetic variation in the human KCNA1 gene which encodes the Kv1.1 voltage-gated potassium (Kv) channel. Affected individuals typically suffer from spastic contractions in the skeletal muscles, loss of both motor coordination and balance, abnormal gait, slurring, eye movement abnormalities, and tremors.
The Kwakwaka’wakw First Nations reportedly used nettles, bladderwrack kelp, and pacific ninebark to treat locomotor ataxia. Ninebark root extract was ingested, kelp was rubbed on the affected limbs, and nettles were rubbed on the soles of the feet after cutting with sharp seashells. And the approach seems to work.
“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,” said Geoffrey W. Abbott, Vice Dean of Basic Science Research and Professor in the Department of Physiology & Biophysics at the UCI School of Medicine. “Prior to this study, we had discovered some synthetic compounds that activate Kv1.1 potassium channels (the dysfunction of which causes episodic ataxia type 1 [EA1]), but they did not rescue function of EA1 mutant channels. We then looked at the literature and found that Kwakwaka’wakw First Nations had used three different plants for ataxia, so we tried them.”
The research team applied extracts of the plants to cloned human Kv1.1 channels, including those carrying EA1 mutations, expressed in frog oocytes, and recorded the effects on channel activity using electrophysiological techniques. Two compounds contained in these plants, tannic acid and gallic acid, were of particular interest because each is able to rescue activity of the EA1-linked mutation-carrying ion channel proteins.
The team has now designed a mouse model of a relatively severe form of human EA1 to test the safety of gallic acid and whole plant extracts. “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,” said Abbott.
This is not the first such discovery from Abbott’s lab, which has been studying the potential of traditional medicines for some time. “It started five years ago, after we found that a small molecule (mallotoxin) from the Mallotus oppositifolius plant (used in African folk medicine as an anticonvulsant) activates neuronal KCNQ2/3 potassium channels, similar to the synthetic anticonvulsant, retigabine,” explains Abbott. “We realized that potassium channels could be a common target for herbal medicines and began intensive research in this area.”
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