Valosin-containing protein (VCP) – multisystem proteinopathy type 1 (MSP-1)

Multisystem proteinopathies are a group of rare, inherited conditions where unusual proteins build up in tissue in the body. Valosin-containing protein (VCP) – MSP type 1 (MSP-1) is the most common type. These conditions can affect a person’s muscles, bones, brain, and motor neurones.

MSP-1 is caused by a pathogenic variant in the VCP gene which helps the body clean up and recycle proteins inside cells.

People with VCP MSP-1 may develop one or more distinct conditions. They may experience progressive muscle weakness, bone disease, dementia, or symptoms similar to motor neurone disease (MND). Symptoms usually begin in adulthood and vary widely, even within the same family.

VCP MSP-1 is also known as VCP disease or inclusion body myopathy associated with Paget’s disease of bone and frontotemporal dementia (IBMPFD).

VCP MSP-1 is a complex condition that can cause a variety of different health problems. A person with VCP MSP-1 may develop one or more conditions affecting the muscles, bones, brain, or nerves. Symptoms usually get worse over time, so regular monitoring and care is key to improving health outcomes.

Below is a description of the main conditions associated with VCP MSP-1 and the symptoms they cause.

Inclusion body myopathy

Myopathy (muscle weakness) is the most common feature of VCP MSP-1, affecting around 9 in 10 people with the condition. It usually begins as proximal weakness, which means weakness in the muscles closest to the centre of the body, such as the shoulders, hips, and torso. In some people, it may instead begin as distal weakness, which affects the muscles further away from the centre of the body, such as the arms, hands, legs, and feet. This muscle weakness can make everyday tasks more difficult, such as lifting objects, climbing stairs, or gripping things.

As the condition progresses, weakness spreads to all muscles throughout the body, including the trunk and, often, the breathing muscles. Most people with inclusion body myopathy eventually need to use a wheelchair. On average, people lose the ability to walk about 13 years after symptoms first appear.

Paget’s disease of bone

Paget’s disease of bone (PDB) affects over half of people with VCP MSP-1. This condition means bones can become enlarged and deformed, which may lead to:

• Bone pain
• Fractures
• Secondary osteoarthritis
• Hearing loss (due to changes in the skull)
• Nerve compression

Everyone with VCP MSP-1 should be routinely monitored for Paget’s disease using periodic nuclear bone scans and blood tests to check for raised ALP (alkaline phosphatase) levels.

Frontotemporal dementia

About 1 in 3 people with VCP MSP-1 develop frontotemporal dementia (FTD). It is a rapidly progressive cognitive syndrome where a person develops early behavioural and language deficits. It typically starts in a person’s 50s or 60s.

Symptoms may include:

• Apathy (lack of motivation or interest)
• Loss of inhibitions (behaving in socially inappropriate ways and acting without thinking)
• Loss of empathy (finding it harder to understand or share other people’s feelings)
• Repetitive or compulsive behaviours
• Overeating
• Trouble finding the right words, understanding language, or speaking clearly

Some people with VCP MSP-1 may also develop other types of cognitive decline that do not fit the full criteria of frontotemporal dementia. It’s important that the cognitive function is routinely monitored in people with a confirmed diagnosis.

Respiratory

Weakness of the muscles used for breathing affects at least 4 in 10 people with VCP MSP-1. Early signs of respiratory problems may include frequent chest infections. As the condition progresses, it can lead to breathing difficulties during sleep.

It’s critical to recognise early signs of respiratory problems so that appropriate treatment and support can be given. If these changes are not properly managed, they can result in respiratory failure, which is a frequent cause of death in VCP MSP-1 patients.

Other less common conditions

Some people with VCP MSP-1 may also develop:

Motor neurone disease (MND) affects around 1 in 10 people VCP MSP-1. MND is a progressive neurodegenerative condition that affects both upper and lower motor neurones. It can cause symptoms such as muscle weakness and loss, twitching, difficulty swallowing and breathing, and sometimes changes in thinking and behaviour.

Parkinson’s disease or parkinsonism is a group of movement disorders that cause symptoms like slow movement (bradykinesia), muscle rigidity, tremors, and problems when standing. These two conditions have been reported in around 4 in 10 people with VCP MSP-1. Other symptoms of Parkinson’s are trouble with movement, changes in speech and facial expression, and difficulty swallowing due to muscle stiffness, weakness, or poor coordination.

Peripheral neuropathy has been diagnosed in some people with VCP MSP-1. Peripheral neuropathy is a condition affecting the nerves outside the brain and spinal cord. It can cause numbness, pain, and weakness in the hands and feet.

Genetic changes

VCP MSP-1 is caused by a change (known as a pathogenic variant) in the valosin containing protein (VCP) gene. There are over 50 disease-causing variants reported in the VCP gene.

Inheritance

The condition is inherited in an autosomal dominant pattern. This means that if one parent has a VCP variant, there is a 1 in 2 chance that it will be passed on to their children.

For more information, see our inheritance and genetics page.

Some of the conditions associated with VCP MSP-1, such as bone disease, dementia, or muscle weakness, can be caused by other, unrelated factors. Because of this, it’s important to have additional diagnostic testing to confirm the cause and help guide clinical care.

There are several ways to identify the symptoms of VCP MSP-1, but the only way to confirm that a VCP gene variant is the cause of these symptoms is through genetic testing.

Genetic testing involves taking a small sample of blood or saliva, which is then analysed in a laboratory to look for changes in the VCP gene.

Before recommending genetic testing, it’s important for a medical professional to conduct a detailed family history. This should focus on conditions linked to VCP MSP-1, such as:

• Muscle weakness
• Cognitive conditions like dementia
• Parkinson’s disease or parkinsonism
• Paget’s disease of bone

This family history assessment is particularly important in people with unexplained adult-onset muscle disease. If there is a family history of any of the associated conditions, and symptoms are present, genetic testing should be considered to confirm the diagnosis.

For more information, see our diagnosis page.

Condition management for someone with VCP MSP-1 depends on the symptoms they experience. There are no approved treatments that slow or stop the progression of the condition, but supportive care and therapies can help manage the symptoms and improve quality of life.

If a person is diagnosed with Paget’s disease of bone, treatment with bisphosphonates is recommended to help relieve bone pain. This is usually given alongside vitamin D to support bone health.

Access to a healthcare team

Everyone with VCP MSP-1 should have access to a multi-disciplinary healthcare team, with clinical appointments at least every six months. Because symptoms vary widely, it’s important that specialists from different areas, such as neurologists and respiratory specialists, are involved in the care of patients. To help guide care, your doctor may arrange tests such as an EMG (which measures electrical activity of the muscles) and regular neurocognitive assessments.

If a person is diagnosed with motor neurone disease, dementia, or Parkinson’s disease, care should be led by a specialist who has experience with that condition. Usually, this will be a neurologist or neuromuscular specialist – doctors who specialise in conditions that affect the muscles and nervous system. If you’re not already seeing a specialist, speak to your GP about a referral.

People diagnosed with frontotemporal dementia (FTD) often need substantial support, as behavioural changes can be challenging for family and carers. Doctors may prescribe medications to help control some of these behavioural symptoms. Regular follow-up with dementia specialists is essential for both patients and carers, ensuring ongoing support, monitoring of symptoms, and appropriate treatment.

Supportive therapies

People living with VCP MSP-1 can experience changes in muscle strength, movement, breathing, speech, and thinking over time. Because this condition can affect many parts of the body, supportive therapies can make a positive difference in daily life. These include:

• Physiotherapy – exercises and treatments to help maintain muscle strength, movement, balance, and flexibility
• Occupational therapy – support to help with daily activities and adapting tasks or environments to maintain independence
• Speech and language therapy – help with communication difficulties, including speaking clearly and understanding language, as well as swallowing support if needed
• Respiratory therapy – support to improve breathing, manage lung health, and address problems like weak breathing muscles or sleep-related breathing issues

These therapies can help maintain independence, mobility, and communication. The effects of VCP MSP-1 on the body should be regularly monitored and managed to help support quality of life and daily activities.

Mobility and aids

Mobility and positioning aids can help reduce falls, conserve energy, and support continued independence both at home and in the community. Relevant aids include:

• Ankle and foot orthotics (AFOs)
• Walking sticks and walkers
• Wheelchairs
• Chair seat risers
• Mobile arm supports
• Hoists and lifting equipment

You may be able to access mobility aids through your local NHS wheelchair or orthotics service, following a referral from your GP, physiotherapist, or occupational therapist. Some equipment may also be provided through local authority social care services or may need to be purchased privately. If you think you would benefit from any of these aids, speak to a member of your healthcare team about an assessment.

Mental health support

Access to appropriate mental health support can help people come to terms with their diagnosis, set and work towards short and long-term goals to improve quality of life, engage in peer or professional support groups, and have difficult conversations with family and friends. It can also reduce the risk of self-harm, and provide support for feelings of fear, grief, and anger.

If you would like to know more about mental health support and where to find help, please see our mental health support page or speak to your GP or healthcare team.

Care guidelines

For more detailed guidance on managing VCP MSP-1, including multidisciplinary care recommendations, see the published care guidelines. These guidelines were created by an international group of over 40 experts.

• Standard of care for patients with valosin-containing protein associated multisystem proteinopathy