ALS: Is there a Role for Klotho?

Dr. Ian C E Hale Ph.D

Lou Gehrig’s Disease, named after the famous baseball player diagnosed in 1939, is now more commonly referred to as amyotrophic lateral sclerosis (ALS). He died 2 years after his diagnosis, aged 37. Gehrig was an unusual case and his high profile brought ALS to public attention. Generally, it strikes the 45-65 age group and is not gender specific. The condition itself was first described by French neurologist Jean-Martin Charcot in 1869. In England it’s commonly called Motor Neuron Disease. 

In many ways that term best describes the condition. Its onset is usually slow; the sufferer may barely notice symptoms or shrug them off as “having a bad day”, “being a bit clumsy” – just a few twitches, stumbles, shaky hands or feet. It all depends on which parts of the brain are attacked first. Unfortunately, it quickly accelerates. It always attacks the voice and throat muscles, making speaking and breathing increasingly difficult. Muscles then start to spasm and tighten all over the body at random, before starting to wither away from disuse (atrophy) leading to an inability to eat, and finally to breathe.  

The cause is unknown, although in around 10% of cases, it affects succeeding generations, so there may be a genetic disposition. It’s very rare. America records only about 5000 cases a year. This is at best a guesstimate because ALS is difficult to diagnose. The diagnosis is made largely by medically excluding other conditions and the experience of the specialist. What we do know is how it works. It disintegrates the motor (muscle control) neurons in the brain. 

They are the roundabout-like structures which direct nerve messages to their proper muscle group for appropriate response. A burn will register on the receptor cluster reporting to the neuron, which then routes the message to the relevant muscles to withdraw the area from the heat quickly. With the motor neurons gone, the muscles no longer work. Only muscle control is affected. The sufferer is in all other ways unimpaired. It’s particularly horrible because the patient knows exactly what’s happening – day-by-day.

Physical therapy helps, swimming especially can slow decline, along with music, learning a sign language, emotional support and riluzole (Rilutek). ALS seems to be characterized by a loss of minerals and vitamins from the body, an unnaturally high level of glutamate and general inflammation. Beyond this, further research is needed.

Preliminary evidence strongly points towards adding Klotho to the armory. The Klotho family is composed of three specialized proteins which have a profoundly protective effect on both the kidneys and brain.  We can stimulate Klotho production by vigorous exercise – Max Interval Training – or controlled fasting. The problem is that as we age our ability to produce enough naturally declines, making supplementing especially important. It’s reckoned that a sizable proportion of the population over 40 have a moderate to serious KL deficiency.

Those 3 Klotho types and their metabolic actions are a very complex study, the details of which may be read at the NCBI link below, from the Journal of Lifestyle Medicine by Ji-Hee Kim, Kyu-Hee Hwang & Seung-Kuy Cha. Yonsei University Wonju, College of Medicine, S Korea. (JLM March 5th 2015). Many other high-quality reports are available online and support Dr Kim’s findings and recommendations.

It is enough to say that from all current research Klotho, and Klotho gene therapy, could prove one of the most important anti-aging proteins yet discovered. It acts as a nootropic, anti-inflammatory, antioxidant and all-body protective agent. It is recommended for all adults over the age of 40 and to anyone in an at-risk group (Familial ALS or Kidney disease) as early in life as possible as a prophylactic agent.

References and Suggested Reading

Cararo-Lopes, Marina Minto, et al. “The relevance of α-KLOTHO to the central nervous system: some key questions.” Ageing research reviews 36 (2017): 137-148.

Kiernan, Matthew C., et al. “Amyotrophic lateral sclerosis.” The lancet 377.9769 (2011): 942-955.

Kuro-o, Makoto. “The Klotho proteins in health and disease.” Nature Reviews Nephrology 15.1 (2019): 27-44.

Zeldich, Ella, et al. “Klotho is neuroprotective in the superoxide dismutase (SOD1 G93A) mouse model of ALS.” Journal of Molecular Neuroscience 69.2 (2019): 264-285. 

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