Plant extracts used by indigenous people may hold promise for the treatment of ataxia

Plants contain the first known compounds to reverse the dysfunction caused by gene mutations underlying certain neuromuscular and coordination problems

A University of California, Irvine-led research team has discovered that extracts from plants used by Kwakwaka'wakw First Nations people 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 Nature Communications in June.

"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, M.D., Ph.D., vice dean for 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 and Pacific ninebark can all correct the function of the mutation-carrying proteins that cause a specific form of ataxia."

Abbott's research team also found that two compounds found in these plants, tannic acid and gallic acid, were each able to rescue the 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," Abbott said.

"Gallic acid in particular is of therapeutic interest because it is already available over the counter as a dietary supplement and has been very well tolerated in toxicity studies."

People with ataxia have an abnormal gait, slurred speech, abnormal eye movements, difficulties with balance and walking, tremors and impaired fine motor skills.

"These mutations can cause other disorders, including epilepsy, so there is therapeutic potential for these conditions as well," Abbott said.

"We have discovered that where modern synthetic drug development techniques have failed to produce a drug that directly rescues the function of EA1-linked mutant channels, 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 created a mouse model of a relatively severe form of human EA1 to test the efficacy and safety of gallic acid and whole plant extracts," Abbott said.

"If the preclinical studies go well, our goal is to move into clinical trials. In parallel, we are synthesizing and testing other plant compounds and derivatives to identify other compounds with potential for treating EA1 and related disorders.

There are several forms of ataxia, an umbrella term for loss of coordination or balance.