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Inclusion Body Myositis: Genomics and Solutions

What is inclusion body myositis?

Inclusion body myositis is a progressive, chronic condition that causes muscle weakness. The muscle weakness slowly progresses and causes difficulty climbing stairs, walking, lifting things, and swallowing.

Men are three times more likely to have inclusion body myositis than women, and symptoms often begin in the 50s or early 60s. While a rare condition, it is more commonly found in people in Norway, Western Australia, Minnesota (US), and Japan.[ref]

Sporadic inclusion body myositis:

Inclusion body myositis (IBM) is an inflammatory myopathy, which means it is a disorder that causes inflammation in the muscles. (“Myo” = muscles; “itis” = inflammation)[ref]

The term ‘sporadic’ here means it arises randomly or due to a currently unknown cause. It differentiates the later in life form of inclusion body myositis from the inherited form that tends to occur earlier in life. (More on the inherited form below.)

The main initial symptoms of inclusion body myositis are weakness in the fingers and wrists and weakness in the quadriceps and ankles. Initial diagnosis can be difficult and often misdiagnosed as arthritis or polymyositis.[ref] Additionally, muscles involving swallowing and facial movement can be impacted.[ref]

Muscle tissue changes in inclusion body myositis:

Biopsies of the muscles impacted by IBM showed inflammation surrounding the muscle fibers. Macrophages and T cells invade the muscle fibers. Additionally, there can be mitochondrial changes in the muscle fibers as well as atrophic fibers.[ref]

Another hallmark of IBM is the formation of rimmed vacuoles and the accumulation of misfolded proteins. It points to an increase in autophagy pathways.[ref]

This image from a good overview of IBM shows the changes in the muscle tissue (creative commons license):

Misfolded proteins:

Similar to age-related neurodegenerative diseases, the muscle tissue in people with IBM shows an accumulation of amyloid-beta protein, tau tangles, and alpha-synuclein. These proteins are ‘myotoxic‘ in the muscle tissue. When accumulated in the brain, these proteins cause Alzheimer’s and Parkinson’s diseases.[ref]

Increased autophagy:

Autophagy is how the body breaks down and recycles different components in the cell. It is often likened to taking out the trash and recycling. The overexpression of proteins associated with autophagy is found in muscle biopsies of sporadic inclusion body myositis.[ref]

In addition to recycling and removing misfolded proteins, defective mitochondria also break down via autophagy. Research is still ongoing on how and why autophagy is disordered in IBM.

Autoimmune or degenerative disease?

It is not yet clear to researchers whether IBM (inclusion body myositis) is an autoimmune disease – or – if it is a degenerative disease with inflammation.[ref]

Some researchers believe it is an autoimmune disease because people with IBM often have T cell abnormalities. Genetic research shows that the sporadic form of IBM is associated with known risk factors for autoimmune diseases.[ref]

Bringing this all together:

Like many complex diseases, there is likely not a simple answer to the cause of IBM. Instead, it may be an interplay between inflammation, the dysregulation of proteins, mitochondrial dysfunction, and changes to autophagy. Somewhere in the mix, autoimmunity may be triggering it.

Hereditary form: Inclusion body myopathy 2

Inclusion body myopathy 2 is a genetic form of the disease caused by mutations in the GNE gene. The GNE gene codes for an enzyme essential for creating sialic acid. People with two copies of mutations in the GNE gene can have lower levels of a type of sialic acid needed to produce certain cell-signaling proteins in muscle cells.[ref][ref]

Compared to the sporadic form, the disease’s familial (genetic) form can start affecting an individual in early adulthood.

Inflammation is not a big component of the hereditary form of inclusion body myopathy 2. Instead, the muscle biopsies show small fibers as well as protein misfolding.[ref]

Inclusion Body Myositis Genotype Report

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If you have inclusion body myositis, talk to your doctor before making any changes to your diet or lifestyle. 

Lifestyle Changes:

Several small studies on mild to moderate exercise show that it may help prevent some of the loss of muscle strength in people with IBM.[ref]

Ketogenic diet:
A case study of a 54-year-old woman with IBM showed that a low-carb, high-fat ketogenic diet helped to maintain strength, improve walking, and increase the quality of life.[ref]

Overall healthy diet:
The Myositis Association recommends a ‘healthy diet’ as necessary… Their recommendations include avoiding processed food, reducing sugar and flour intake, and eating vegetables and fish.[ref] (To me, this seems to be an obvious starting point that most people with IBM are likely already doing.)

Supplements for inclusion body myositis:

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Related Article and Topics:

Autophagy genes
Autophagy is a general term for cellular pathways that move something from the cytoplasm of the cell into the lysosome for degradation.

TNF-alpha and Inflammation
Tumor necrosis factor (TNF) is an inflammatory cytokine that acts as a signaling molecule in our immune system. In an acute inflammatory situation, TNF-alpha plays an essential role in protecting us, but genetically higher TNF-alpha levels are also linked to chronic inflammatory diseases.

AGEs and RAGEs
The receptor for Advanced Glycation Endproducts (RAGEs) is a target for HMGB1

Rapamycin, mTOR, and Your Genes
Learn about the recent research on rapamycin and how your genetic variants impact mTOR.



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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.