In a groundbreaking discovery, researchers at the University of California, Irvine have identified the potential of plant extracts used in the traditional botanical medicine practices of the Kwakwaka’wakw First Nations people.
These extracts have shown the ability to restore the function of ion channel proteins that carry mutations responsible for human episodic ataxia, a movement disorder.
The study, titled “Native American ataxia medicines rescue ataxia-linked mutant potassium channel activity via binding to the voltage sensing domain,” was recently published in Nature Communications, shedding light on the promising medicinal properties of these plant extracts.
Episodic ataxia 1 (EA1) is a neurological disorder characterized by abnormal movements, impaired balance, slurred speech, eye movement irregularities, tremors, and difficulties with fine motor skills.
It is caused by mutations in the KCNA1 gene, responsible for encoding Kv1.1, a voltage-gated potassium channel vital for the normal functioning of the human nervous system.
Led by Dr. Geoffrey W. Abbott, the vice dean of basic science research and a professor in the Department of Physiology & Biophysics at the UCI School of Medicine, the research team discovered that extracts from stinging nettle, bladderwrack kelp, and Pacific ninebark can correct the malfunctioning ion channel proteins carrying specific forms of ataxia-related mutations.
Excitingly, the team also identified two compounds, tannic acid and gallic acid, present in these plants, which exhibited the ability to restore the activity of the mutation-carrying ion channel proteins associated with EA1.
According to Dr. Abbott, “These plant compounds are the first known substances capable of rescuing the activity of Kv1.1 carrying EA1-linked loss-of-function sequence variants. Gallic acid, in particular, is of significant interest for therapeutic purposes due to its availability as a nutritional supplement over the counter, as well as its well-tolerated nature in toxicity studies.”
The potential of these discoveries extends beyond the treatment of ataxia alone.
Since these mutations can also lead to other conditions, such as epilepsy, there is hope for developing therapeutic interventions for a broader range of disorders.
Dr. Abbott emphasized, “Where modern synthetic drug development techniques have failed, traditional botanical medicine developed by North American First Nation peoples has succeeded.
Our findings pave the way for further investigation into the efficacy of these plant-derived compounds through pre-clinical and clinical studies.”
To facilitate this exploration, the research team has created a mouse model that mimics a severe form of EA1.
This model will enable them to evaluate the effectiveness and safety of gallic acid, as well as whole plant extracts.
Positive results from pre-clinical studies will serve as a stepping stone for initiating clinical trials.
In parallel, the team is actively involved in synthesizing and testing other plant compounds and derivatives to identify additional substances with the potential to treat EA1 and related disorders effectively.
Ataxia encompasses a range of conditions characterized by impaired coordination and balance.
This breakthrough research has the potential to revolutionize the treatment landscape for individuals affected by these debilitating disorders.
Collaborating with Dr. Abbott on this groundbreaking study were esteemed researchers including Drs. Rian Manville, J. Alfredo Freites, Doug Tobias (UC Irvine), and Richard Sidlow (Valley Children’s Hospital).
Research Holds Promise for Traditional Medicine’s Role in Treating Ataxia
Groundbreaking research conducted at the University of California, Irvine has revealed that extracts from plants traditionally used in the medicinal practices of the Kwakwaka’wakw First Nations people could offer a breakthrough treatment for human episodic ataxia.
A team led by Dr. Geoffrey W. Abbott has found that these plant extracts can restore the function of ion channel proteins carrying mutations responsible for the movement disorder.
The research, published in Nature Communications, highlights the potential therapeutic applications of traditional botanical medicine.
Episodic ataxia 1 (EA1) is a neurological disorder characterized by difficulties with balance and coordination, abnormal gait, tremors, and disrupted fine motor skills.
It is caused by inherited mutations in the KCNA1 gene, which encodes a voltage-gated potassium channel known as Kv1.1.
This channel is crucial for the proper functioning of the human nervous system.
By studying extracts of stinging nettle, bladderwrack kelp, and Pacific ninebark, the research team discovered their ability to restore the function of mutation-carrying proteins associated with EA1.
The team also identified two compounds, tannic acid and gallic acid, present in these plant extracts that were able to rescue the activity of the ion channel proteins linked to EA1.
Of particular interest is gallic acid, as it is already available as a nutritional supplement and has shown good tolerance in toxicity studies.
The discovery of these plant compounds represents a significant advancement in the search for a direct treatment for EA1 and related conditions.
Dr. Abbott emphasizes the importance of this breakthrough, stating that traditional botanical medicine has succeeded where modern synthetic drug development techniques have fallen short.
The plant extracts and compounds discovered have the potential to not only correct the function of the mutation-carrying proteins but also to address other disorders, including epilepsy, that may arise from these mutations.
To further investigate the efficacy of these plant-derived compounds, the research team plans to conduct pre-clinical and clinical studies.
They have developed a mouse model that replicates a severe form of human EA1, allowing them to test the safety and effectiveness of gallic acid and whole plant extracts.
Positive outcomes in the pre-clinical studies will pave the way for clinical trials. Additionally, the team is actively exploring other plant compounds and derivatives to identify further potential treatments for EA1 and related disorders.
The implications of this research are far-reaching, as ataxia encompasses various disorders characterized by a loss of coordination and balance.
With this groundbreaking study, the University of California, Irvine researchers have opened up new possibilities for the treatment of these conditions.
Collaborating with Dr. Abbott on this significant breakthrough were Drs. Rian Manville, J. Alfredo Freites, Doug Tobias (UC Irvine), and Richard Sidlow (Valley Children’s Hospital).
Frequently Asked Questions (FAQ)
Episodic ataxia is a neurological disorder characterized by symptoms such as abnormal gait, balance difficulties, slurred speech, tremors, and disrupted fine motor skills. It is caused by inherited mutations in the KCNA1 gene, which affects the function of a voltage-gated potassium channel called Kv1.1.
The researchers at the University of California, Irvine found that extracts from plants used in the traditional medicine practices of the Kwakwaka’wakw First Nations people can rescue the function of ion channel proteins carrying mutations responsible for episodic ataxia. Specifically, extracts from stinging nettle, bladderwrack kelp, and Pacific ninebark were able to correct the function of the mutation-carrying proteins associated with a specific form of ataxia.
The researchers identified two compounds in the plant extracts, namely tannic acid and gallic acid, that were able to rescue the activity of the mutation-carrying ion channel proteins linked to episodic ataxia. Gallic acid, in particular, showed promise as it is already available as a nutritional supplement and has demonstrated good tolerance in toxicity studies.
Yes, these plant compounds are the first known substances to rescue the activity of the Kv1.1 channel carrying EA1-linked loss-of-function sequence variants. This discovery is significant as previous synthetic drug development techniques have been unsuccessful in directly addressing the mutant channel function associated with episodic ataxia.
The mutations in the KCNA1 gene can also cause other disorders, including epilepsy. Therefore, the findings from this research hold promise for the development of treatments for a broader range of conditions beyond episodic ataxia. Traditional botanical medicine, as developed by North American First Nation peoples, may provide valuable insights and solutions for therapeutic interventions.
Further research is needed to explore the efficacy of the plant-derived compounds in pre-clinical and clinical studies. The research team has created a mouse model that simulates a severe form of human episodic ataxia. They plan to evaluate the safety and effectiveness of gallic acid and whole plant extracts using this model. If the pre-clinical studies yield positive results, the team aims to proceed with clinical trials. Additionally, the researchers are actively synthesizing and testing other plant compounds and derivatives to discover additional potential treatments for episodic ataxia and related disorders.
The research was led by Dr. Geoffrey W. Abbott, vice dean of basic science research and a professor in the Department of Physiology & Biophysics at the UCI School of Medicine. The team also included Drs. Rian Manville, J. Alfredo Freites, Doug Tobias (UC Irvine), and Richard Sidlow (Valley Children’s Hospital), among others.
Currently, there is no known cure for episodic ataxia. However, the discovery of these plant extracts and compounds offers potential avenues for the development of treatments that could rescue the function of ion channel proteins and alleviate the symptoms associated with the disorder. Further research and clinical trials
