• Frequent tripping and falling: This can be due to buckling of the knees due to thigh weakness and may be the first sign of IBM.
• Weakness in the wrists and fingers: This may lead to challenges with pinching, buttoning, and holding onto objects.
• Struggling to rise from a seated position.
• Difficulty ascending stairs.
• Feeling fatigued after prolonged standing or walking.
• Dysphagia, or difficulty swallowing. At least 40 percent of IBM patients report this condition. It can also cause liquids to come out of the nose and lead to breathing in food or drink into the lungs. Weakness in throat muscles, known as dysphonia, can also make it difficult to speak.
• Muscle cramping and pain.

• Asymmetrical and distal muscle weakness: This condition sometimes affects only one side of the body, accompanied by an extremely gradual progression of IBM.
• Myalgia: Myalgia refers to pain and discomfort in the muscles and soft tissues of the body. This pain is typically dull and can affect one or multiple muscles.
• Muscle atrophy: Atrophy, the thinning or loss of muscle bulk, may occur most often in the forearm and quadriceps muscles of the legs.
• Difficulty lifting the arms.
• Weakness in the quadriceps, hands, forearms, and ankles.
• Unstable knees.
• Decreased walking ability.
• Impaired hand dexterity.
• Drop foot: A patient may have trouble lifting the front of their foot.

• Inflammation: The inflammatory aspect involves immune cells—particularly cytotoxic CD8+ T-cells and macrophages, which normally eliminate faulty cells—becoming misdirected and invading healthy muscle fibers. These immune cells and CD4+ T-cells incite an inflammatory response within the muscles. This immune activation is likely driven by specific antigens (toxic or foreign substances), as suggested by the presence of numerous antigen-presenting cells (APCs) within muscle fibers. However, it remains unclear whether this is a primary inflammatory disorder or if the inflammation is secondary.
• Degeneration: On the degenerative side, abnormal processing of proteins associated with aging can lead to the deposition of toxic polymers (large, long-chain, organic molecules made up of repeating smaller units called monomers) in the muscles, causing damage. The presence of degenerative protein beta amyloid in the muscle fibers of IBM patients supports the idea of a degenerative pathway. This beta-amyloid protein has been shown to stimulate the production of interleukin-6 by human myoblasts (immature muscle cells), which can further aggravate the local immune response.
• Genetics: Genetic inclusion body myopathies can be inherited via dominant or recessive patterns. Dominant disorders need only one genetic flaw to manifest, while recessive require both parents to pass on the flaw in the same gene. The disease is not directly inherited in s-IBM patients, but an increased presence of the human leukocyte antigen (HLA) DR52 and DR3 genes suggests a potential autoimmune predisposition. Thus, while some individuals may have a genetic predisposition to IBM, the condition is generally not inherited.

• Sporadic inclusion body myositis (s-IBM): Most IBM cases are s-IBM, whose cause is unknown. It involves an autoimmune component, where the body attacks its own tissues. However, other factors may contribute, and the exact triggers remain unidentified. A subtype of s-IBM called familial inflammatory sIBM affects at least two siblings.
• Hereditary inclusion body myopathy (h-IBM): H-IBM comprises a diverse range of disorders inherited through either autosomal recessive or dominant patterns. H-IBM cases are rare and associated with genetic factors. Unlike myositis (hence the name “myopathy”), muscle inflammation is not typically a significant feature of h-IBM. Its symptoms often appear much earlier than those of s-IBM—sometimes in a person’s 20s. Thigh muscles are usually spared until the disease reaches advanced stages. In addition, the term “hereditary inclusion body myopathy” is becoming less used, as specific disorders are nowadays named based on their underlying genetic mutations. For instance, h-IBM type 2 is now called GNE myopathy due to its association with a mutation in the GNE gene.

• Age: IBM symptoms typically start appearing after the age of 50.
• Sex: IBM has a higher male-to-female ratio, estimated at around 3:1, in contrast to other autoimmune-related diseases.
• Genetics: Genetics, such as the HLA DR3 gene, can predispose some people to develop IBM.
• Certain conditions: Research has shown that individuals with a history of high blood pressure, high cholesterol levels, heart attacks, heart failure, pneumonia, anemia, or diabetes are at higher risk of developing IBM. Those infected with HIV may develop myositis, as can those with the human T-cell leukemia virus type 1 (HTLV-1 virus). In addition, some cases of myositis have been associated with Coxsackie B virus infection.
• Some medications: Certain medications may also trigger IBM. For instance, dasatinib, considered a safe drug for treating chronic myeloid leukemia, can lead to IBM in rare cases. Cholesterol-lowering statins such as atorvastatin, simvastatin, and rosuvastatin may induce autoimmune myopathy and cause IBM. Colchicine, used to prevent or treat gout, familial Mediterranean fever, cirrhosis, primary biliary cirrhosis, and pseudogout, has also been suspected in IBM cases. Interferons, used in treating viral infections, autoimmune diseases (e.g., multiple sclerosis), and certain cancers, may also induce s-IBM.

• Acid maltase deficiency
• Chronic inflammatory demyelinating polyradiculoneuropathy
• Late-onset distal myopathies
• Motor neuron disease
• Myofibrillar myopathies
• Overlap myositis
• Post-polio syndrome

• Evaluation of physical symptoms and medical background: A specialist will first consider an individual’s personal and family medical history and check symptoms to document the pattern of weakness in the muscles.
• Blood tests: A blood test can check the level of creatine kinase (CK), an enzyme that leaks out of damaged muscle fibers. In IBM, CK levels may be only slightly increased, moderately increased up to 10 times the normal level, or even within the normal range. This is different from other inflammatory myopathies, where CK levels are typically very high, often reaching 15 times the normal level. In addition, a newer blood test can detect an antibody called anti-cN1A or anti-NT5C1A in the blood. This test is positive in about 50 percent of IBM patients and can help differentiate IBM from polymyositis. The test can also detect other autoimmune diseases. However, it may not be widely available.
• Nerve conduction studies: Nerve conduction studies may be performed to evaluate the speed of nerve impulse transmission and detect disruptions in nerve signals. During a nerve conduction study, electrodes are placed on the skin to stimulate a nerve with a mild electrical impulse. Another electrode records the response, and the resulting electrical activity is measured. This process is repeated for each nerve being tested. The speed of nerve impulses is calculated by measuring the distance between electrodes and the time it takes for electrical signals to travel between them. A nerve conduction study is often used along with electromyography to tell the difference between a nerve disorder and a muscle disorder.
• Electromyography (EMG): Related to the nerve conduction study, EMG evaluates the electrical activity of muscles and their controlling nerves. In IBM, abnormal electrical impulses may be observed, and EMG may rule out neurological disorders. While EMG can aid in confirming muscle involvement, it does not provide a definitive diagnosis. Results can be misleading, suggesting neurological disorders such as motor neuron disease in some cases.
• Imaging tests: Muscle imaging using magnetic resonance imaging (MRI) or computerized tomography (CT) scans can reveal distinct patterns of muscle involvement linked to IBM. This information aids in confirming an IBM diagnosis and differentiating it from other types of myositis.
• Muscle biopsy: The definitive test for IBM is a muscle biopsy, which entails extracting a small muscle sample and examining it under a microscope. Various stains are applied to emphasize different muscle components. In IBM, inclusion bodies are typically found within muscle cells.
• Genetic testing: Genetic tests may identify potential genetic factors.

• Onset of symptoms after age 45
• Duration of symptoms exceeding 12 months
• Serum creatine kinase levels less than 15 times the upper limit of normal levels

• Knee extension weakness is greater or equal to hip flexion weakness
• Finger flexion weakness is greater than shoulder abduction weakness

• Presence of endomysial inflammatory infiltrate: Inflammatory cells within the connective tissue envelop individual muscle fibers.
• Presence of rimmed vacuoles: Rimmed vacuoles are localized areas of muscle fiber destruction.
• Protein accumulation or 15- to 18-nanometer filaments.
• Upregulation of major histocompatibility complex (MHC) class 1: There is an increase in the expression or production of MHC class 1 molecules on the surface of cells.

• Clinicopathologically defined IBM: Required criteria + one or both clinical criteria + first three pathological criteria
• Clinically defined IBM: Required criteria + both clinical criteria + one or more, but not all, pathological criteria
• Probable IBM: Required criteria + one clinical criterion + one or more, but not all, pathological criteria

• Inability to walk, necessitating assistive tools such as wheelchairs.
• Dysphagia.
• Aspiration pneumonia: The risk of aspiration pneumonia is highest for individuals with inflammatory myopathies such as IBM. Aspiration pneumonia has relatively high rates of recurrence and mortality.
• Compromised breathing due to diaphragm weakness and other respiratory complications, such as respiratory failure.
• Stumbling during walking and injurious falls.
• Development of pressure ulcers, muscle wasting, and other mobility-related issues.
• Challenges with everyday activities.
• Decreased self-reliance.
• Depression due to reduced quality of life.

• Peripheral neuropathy: IBM patients are 2.7 times more likely to develop peripheral neuropathy. Peripheral neuropathy includes various conditions characterized by damage to the peripheral nervous system, which serves as a communication network transmitting signals between the brain, spinal cord (central nervous system), and the rest of the body.
• Sjögren’s syndrome: IBM patients are 6.2 times more likely to have Sjögren’s syndrome, a chronic autoimmune condition where the immune system targets and attacks the glands responsible for producing moisture in the eyes, mouth, and other areas, resulting in dryness.
• Blood cancers: Individuals with IBM are 3.9 times more likely to experience hematologic malignancies, particularly T-cell large granular lymphocytic leukemia, but are not at higher risk of other cancers.

1. Medications

• ABC008: Biotechnology company Abcuro is currently conducting a phase 2/3 clinical trial for ABC008, an antibody aimed at targeting highly cytotoxic T-cells found in the muscles of individuals with IBM. These T-cells are believed to contribute significantly to muscle damage in the disease. ABC008 selectively eliminates the majority of highly cytotoxic T-cells while sparing protective T-cells and white blood cells, thus minimizing potential harm. The U.S. Food and Drug Administration (FDA) has granted an Orphan Drug Designation for ABC008 for the treatment of IBM.
• Alemtuzumab: A small clinical trial involving 13 IBM patients tested alemtuzumab, a drug typically used for leukemia and multiple sclerosis. The drug, which depletes specific immune cells, showed promising results in slowing IBM progression and improving strength in some patients. However, further research is needed to confirm its effectiveness.
• Arimoclomol: Arimoclomol is a substance thought to help fix specific proteins in muscle cells, preventing them from clumping. In a pilot study with IBM patients, the treatment was safe and well-tolerated. It also reduced important markers of IBM in mouse lab models representing different aspects of the disease and improved disease characteristics and muscle function of the mice. However, recent results from a large, randomized controlled trial showed the drug did not improve outcomes.
• Azathioprine: Immunosuppressive and immunomodulating drugs such as azathioprine have been used to address IBM’s inflammatory and muscle-wasting aspects. However, they weren’t able to reverse or slow the progression of the disease, and many clinicians believe their possible side effects outweigh the potential benefits, particularly for patients who also have other autoimmune diseases.
• Bimagrumab: Bimagrumab, or BYM338, is a human antibody that addresses muscle loss and weakness. In a pilot trial with s-IBM patients, it appeared to increase muscle mass and function. If the drug is approved, bimagrumab’s potential off-label use for s-IBM will be considered.
• Follistatin: Follistatin, also referred to as AAV1-FS344, is a protein delivered through gene therapy that enhances muscle strength and performance. It blocks certain proteins in the body that slow muscle growth and cause muscle loss, so it’s being explored as a potential treatment to improve muscle health and counteract muscle wasting in IBM.
• Glucocorticoids: Glucocorticoids are a type of corticosteroid with anti-inflammatory and immunosuppressive properties that some doctors may consider. These properties make them useful in treating conditions related to inflammation and immune system dysfunction. However, corticosteroids typically do not effectively treat this disease.
• Intravenous immunoglobulin (IVIG): IVIG therapy involves using blood plasma to manage dysphagia symptoms in some individuals. It is administered through an infusion that takes several hours. The treatment typically spans up to four months, including an induction phase and three maintenance cycles, to assess improvement in swallowing difficulties. If no benefit is observed, IVIG therapy is usually discontinued.
• Methotrexate: Limited evidence indicates that methotrexate, an immunosuppressive drug, can potentially lead to disease stabilization or modest improvement in some IBM patients.
• Sirolimus: Sirolimus, or rapamycin, is usually used to prevent kidney transplant rejection. A previously conducted phase 2b clinical trial investigated its use for IBM with promising results, and a phase 3 trial to further evaluate its efficacy is currently underway.

2. Physical, Speech, and Psychological Therapies

• Occupational therapy: Occupational therapists provide advice and specialized equipment to address daily challenges for individuals with IBM. Equipment includes utensils with ergonomic handles for better grip, tools to aid in climbing stairs, ramps for accessibility, walking aids, lift chairs, and guidance on optimizing bathroom facilities.
• Speech therapy: Swallowing difficulties in IBM can lead to food or liquid entering the windpipe, causing coughing, chest infections, and weight loss. Speech therapists can help manage these swallowing issues.
• Psychological therapy: Due to IBM’s chronic nature, psychological therapy or consulting a rehabilitation psychologist may be beneficial.

3. Adjuvant Therapies

4. Surgery

5. Possible Future Treatments

• Reducing endoplasmic reticulum stress: The endoplasmic reticulum (ER) is a compartment within a cell that plays a significant role in protein synthesis and folding. ER stress can occur when misfolded proteins accumulate in the ER, leading to cell dysfunction and IBM. Reducing ER stress involves decreasing protein overload and removing misfolded proteins.
• Promoting autophagy: Autophagy is a process where cells degrade and recycle damaged or unnecessary components to maintain cellular health, similar to a cellular self-cleaning mechanism. In muscles, a lack of autophagy can cause muscle atrophy and the accumulation of harmful materials within cells. In s-IBM, autophagy appears to be defective.
• Removing toxic protein aggregates: IBM involves the invasion of T-cells and the formation of protein aggregates such as rimmed vacuoles and inclusion bodies. Protein aggregates can also trigger immune responses and inflammation, and persistent immune activation can lead to T-cell large granular lymphocytic leukemia that resists treatment, possibly explaining the progression from polymyositis to IBM. These protein aggregates can hinder cell functions, spread within cells like an infectious agent, and prevent muscle cell repair after damage, ultimately causing weakness and muscle shrinkage. Therefore, treatments centered on removing these protein aggregates may be an area of future exploration.

1. Medicinal Herbs

• Schisandra (Schisandra chinensis): In addition to Schisandra’s antioxidant, anti-allergen, antidepressant, and anti-anxiety properties, it decreased muscle cell inflammation and promoted autophagy in animal studies. It also improved muscle strength and stamina in rats.
• Turmeric (Curcuma longa): Turmeric can reduce inflammation and promote muscle recovery, but consuming it may lead to diarrhea, headache, and rash.
• Ashwagandha (Withania somnifera): Revered in the Indian Ayurvedic tradition as a tonic, particularly for the nerves, Ashwagandha is used for a wide range of health conditions. It is an anti-inflammatory and improves mitochondrial health and energy levels, but it may cause side effects such as rhinitis, constipation, and decreased appetite.
• Ginseng (Panax ginseng): Ginseng can enhance physical endurance, focus, and memory, boost immune system function, delay aging effects, and alleviate symptoms related to various health issues such as respiratory and heart conditions, depression, and anxiety. However, consuming it may affect sleep quality and blood sugar levels.

2. Supplements

• Creatine monohydrate: Athletes often use creatine monohydrate (creatine for short) to enhance muscle strength and size. Our bodies naturally produce creatine, and it’s found in foods such as meat and fish. Supplementation can boost muscle creatine levels, which is particularly beneficial for vegetarians. A daily dosage of around 3 grams is commonly advised for optimal effects. The supplement is generally considered safe.
• Mitochondrial cocktail: Some supplements are believed to support mitochondria, the energy-producing units in our cells often affected in IBM. A combination of such supplements called the “mitochondrial cocktail,” which includes Coenzyme Q10, L-carnitine, B-complex vitamins, and antioxidants, has been proposed as a potential treatment. However, these supplements haven’t been extensively researched and can be costly. It’s essential to consult your doctor before using them.

3. Diet

4. Mind-Body Practice and Acupuncture

• Regular exercise: Regular cardiovascular and strength-training exercises will discourage muscle wasting.
• Healthy diet: Choosing high-quality, whole foods over processed ones is essential.
• Stress management: Controlling stress will lower your odds of weakening your immune system and reduce systemic inflammation.
• Regular health checkups: Early detection and management of IBM can help maintain muscle function as much as possible.
• Sleep hygiene: Get seven or eight hours of sleep as often as possible and maintain a consistent bedtime routine.
• Avoid harmful substances: Avoiding smoking, limiting alcohol, and reducing exposure to toxins wherever possible will contribute to resilience.