Plant compound shows potential for treating ALS and dementia

A team of scientists has recently identified a widely available, naturally occurring plant compound that appears to safeguard nerve cells from deterioration, potentially offering a breakthrough in the treatment of ALS (amyotrophic lateral sclerosis) and dementia. 

Many fruits and vegetables, including kale, endives, and berries, naturally contain the compound kaempferol, which is an antioxidant.

Despite its common presence in our diet, new findings reveal that the compound kaempferol’s benefits for nerve cell health may far exceed what we previously understood.

“It’s exciting to discover a naturally occurring compound that may help people suffering from ALS or dementia,” said Smita Saxena, a professor of physical medicine and rehabilitation at the University of Missouri School of Medicine and the lead investigator on this study.

“We found this compound had a strong impact in terms of maintaining motor and muscle function and reducing muscle atrophy.”

A unique plant compound

Kaempferol is a flavonoid, a class of molecules prized for their antioxidant and anti-inflammatory properties. In this research, scientists honed in on how kaempferol might help nerve cells deal with two major sources of stress. 

First, neurons depend on mitochondria to produce the energy they need to function. If these mitochondria falter, neurons become less able to maintain the electrical signals and chemical communications essential to muscle control. 

Second, neurons rely on the endoplasmic reticulum (ER) to assemble and process proteins correctly. In many neurodegenerative diseases, including ALS, the ER is under tremendous strain, leading to protein misfolding and cell damage.

In nerve cells sampled from ALS patients, the plant compound significantly boosted the cells’ energy production and reduced ER stress.

The experts argued that this is one of the first compounds scientists have identified to directly act on both mitochondria and the ER at once. That double-targeting mechanism could be a potent means of slowing or preventing neuronal loss.

Compound has potential to fight ALS

ALS is a progressive condition that disrupts muscle control, often beginning with twitching or weakness and ending in complete paralysis. Current treatments for ALS are limited and generally only slow progression marginally. 

As a result, the demand for new therapeutic options is high. Kaempferol’s ability to bolster two of the cell’s most vulnerable processes – energy generation and protein management – makes it stand out as a promising candidate.

Lab tests showed that kaempferol not only delayed the deterioration of nerve cells but also retained motor function in experimental models. 

According to Saxena, the compound is particularly interesting because it seems effective even after symptoms of ALS begin manifesting.

Many potential therapies lose their efficacy once a disease’s clinical signs emerge, so a compound that works in symptomatic patients could represent a major step forward.

Obstacles to overcome

Despite these promising findings, there are two major challenges to transforming kaempferol into a widely used treatment. 

The first issue is that the human body absorbs it poorly. While foods such as kale or berries do contain kaempferol, you would need to eat staggering amounts – at least 10 to 11 pounds of kale in a single day – to reach the dosage levels shown to be beneficial in laboratory conditions.

This poor absorption means only a small fraction of dietary kaempferol reaches nerve cells.

Second, the blood-brain barrier adds another challenge. While it protects the brain from harmful substances, it also blocks helpful compounds like kaempferol from reaching target cells in effective amounts. Even if one manages to consume enough kaempferol, delivering it to the brain is another significant challenge.

“Our bodies don’t absorb kaempferol very well from the vegetables we eat,” Saxena said. “Because of this, only a small amount reaches our tissues, limiting how effective it can be. We need to find ways to increase the dose of kaempferol or modify it so it’s absorbed into the bloodstream more easily.”

Paving the way for clinical tests

To address these issues, Saxena’s team is experimenting with improved delivery strategies. One leading idea is to use lipid-based nanoparticles as carriers.

Researchers have already explored these tiny fat-based spheres in other areas of medicine – particularly vaccines – to ferry molecules across biological barriers.

By packaging it in this way, scientists can help it dodge some of the body’s natural defense systems and enable more of it to reach the neurons. Essentially, neurons would take up these nanoparticles more efficiently, delivering a potent dose of kaempferol to the exact spot where it’s needed.

Saxena’s lab aims to finalize their nanoparticle formulations and begin testing them in model systems later this year.

If these trials are successful, it could pave the way for clinical testing in humans, a process that could eventually yield a new class of neuroprotective drugs derived from compounds found in common foods.

Plant compound’s potential beyond ALS

While the research is focused on ALS, the mechanisms targeted by kaempferol – such as energy metabolism and protein folding – are also at play in other neurodegenerative diseases, including Alzheimer’s and Parkinson’s.

This raises the possibility that a kaempferol-based therapy, once refined, could have broader applications in neurology.

By stabilizing both energy production and protein management, there’s a chance the compound could alleviate several types of degenerative stress in neurons.

Of course, researchers must still conduct substantial studies before they can consider kaempferol a bona fide treatment. Still, these early results renew hope in a field that desperately needs effective solutions.

For now, this work reminds us that even a molecule we routinely consume in fruits and vegetables may harbor remarkable secrets – if only we can figure out how to harness its power.

The study is published in the journal Acta Neuropathologica Communications.

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