Simply Stated: Understanding VCP-Associated Multisystem Proteinopathy (VCP-MSP)

Valosin-containing protein (VCP)-associated multisystem proteinopathy (VCP-MSP), also sometimes called VCP disease, is a rare inherited condition caused by changes in the VCP gene. These gene changes can affect multiple body systems, resulting in a range of clinical features. Historically, VCP-MSP was known as inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD), reflecting three of its recognized features. However, since VCP-MSP can affect other systems and present in many different ways, it is now recognized as part of a broader group of conditions called multisystem proteinopathies. Its full name is VCP-associated multisystem proteinopathy, and it is also referred to as multisystem proteinopathy type 1 (MSP1). Fewer than 2,000 people worldwide have been reported to have VCP-MSP, but the actual number is likely higher, with many individuals remaining undiagnosed.

Cause of VCP-MSP

VCP-MSP is caused by a change (pathogenic variant) in the VCP gene, which provides instructions for making the VCP protein that helps cells process and remove damaged or unwanted proteins in the cell. These pathogenic variants can disrupt normal cell functions and contribute to damage in the muscles, bones, and brain, although the exact mechanisms are not fully understood.

VCP-MSP is inherited in an autosomal dominant pattern, which means that a person only needs one copy of the defective VCP gene, passed down from one parent, to have the condition. Each child of a person with VCP-MSP has a 50% chance of inheriting the variant. In some cases, the variant appears for the first time in a person with no known family history.

Symptoms of VCP-MSP

VCP-MSP can affect multiple body systems, and symptoms vary widely from person to person, even within the same family. Symptoms typically begin in adulthood and may progress over time, although childhood-onset cases have also been reported and may have a different clinical presentation.

Common symptoms and features include:

• Muscle weakness: Progressive weakness, often affecting the hips, thighs, shoulders, and arms, which can make walking, climbing stairs, or lifting the arms difficult.
• Bone disease: Paget disease of bone, which can cause bone pain, deformities, and fractures.
• Cognitive and behavioral changes: Frontotemporal dementia, which can affect personality, behavior, language, speech, and decision-making.
• Other neurological symptoms: Some individuals develop additional neurological features, including motor neuron disease such as amyotrophic lateral sclerosis (ALS), parkinsonism, or peripheral nerve problems that can affect movement and sensation.
• Heart involvement: Some people develop cardiomyopathy, a weakening of the heart muscle, so periodic heart evaluation is recommended.
• Other symptoms: Some people experience respiratory muscle weakness, balance difficulties, pain, or mood changes.

Not everyone develops all of these symptoms. VCP-MSP can affect different combinations of body systems, and its presentation and progression can vary considerably among different people.

To learn more about the signs, symptoms, causes, and management of VCP-MSP the following resources may be helpful:

• Standard of Care for VCP-associated multisystem proteinopathy: The consensus care guidelines developed by more than 40 international experts across neurology, cardiology, pulmonology, therapy, genetics, and other fields, convened by Cure VCP Disease and published in the Orphanet Journal of Rare Diseases (Korb, Peck, et al., 2022). This is the primary reference for diagnosing and managing VCP-MSP.
• Provisional practice recommendation for the management of myopathy in VCP-associated multisystem proteinopathy: Management recommendations for muscle weakness related to VCP-MSP (Roy, Peck et al., 2023)
• Genotype-phenotype correlations in valosin-containing protein disease: a retrospective muticentre study: A clinical review of signs and symptoms (Schiava, Ikenaga et al. , 2022)
• Neuromuscular Disorders article by Romano, et al. (2026)
• Cure VCP Disease: Resources, support, and information for individuals and families affected by VCP-MSP
• Cure VCP Disease Patient Registry: An international registry where people living with VCP-MSP can share their health information to support research.

Diagnosis of VCP-MSP

Diagnosis is based on clinical evaluation and genetic testing. Symptoms can overlap with other conditions, so genetic testing to identify a pathogenic variant in the VCP gene is essential to confirm the diagnosis. Evaluation may include:

• Medical and family history to assess symptoms and inheritance patterns
• Neurological examination to evaluate muscle strength, mobility, cognitive impairment, and other neurological symptoms
• Blood tests to measure creatine kinase (CK), which may be elevated due to muscle damage, and ALP level, which may be elevated due to Paget’s disease of bone
• Genetic testing to identify a pathogenic variant in the VCP gene
• Additional tests, such as muscle biopsy or imaging, when indicated by symptoms

Current management of VCP-MSP

There is currently no cure or disease-modifying therapy for VCP-MSP. Bisphosphonates are available to treat Paget’s disease of bone. Primary treatment for other symptoms focuses on treating symptoms, maintaining function, and addressing complications as they arise. The Standard of Care for VCP-associated multisystem proteinopathy, developed by more than 40 international experts convened by Cure VCP Disease and published in 2022, is the leading guide for clinicians and families when planning care.

Care may include:

• Physical and occupational therapy to maintain mobility, strength, and independence
• Respiratory assessment and support if breathing muscles become affected
• Cardiac evaluation to check for heart involvement
• Neurological and cognitive care to manage changes in movement, behavior, or thinking
• Management of Paget disease of bone and other musculoskeletal complications, when present
• Nutritional support and swallowing assessment if eating or swallowing becomes difficult
• Psychological support and genetic counseling for affected individuals and their families

Since VCP-MSP affects multiple body systems, care is typically coordinated by a multidisciplinary team that may include neurologists, physical therapists, occupational therapists, , pulmonologists, cardiologists, bone specialists, geneticists, and other healthcare providers as needed.

Evolving research and treatment landscape

Research is advancing the understanding of VCP-MSP and how it progresses. Scientists are also investigating potential treatments, including approaches that target VCP activity or reduce the effects of pathogenic gene variants. These approaches are experimental, however, and no disease-modifying treatment has yet been developed.

Notably, natural history studies are identifying ways to measure changes in muscle strength, mobility, and daily functioning, helping researchers prepare for future clinical trials. Examples include:

• Natural History of Multisystem Proteinopathy (MSP) Study (CReATe Consortium, University of Miami) – This multisite study is led through the University of Miami as part of the Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium. It follows adults with a genetically confirmed variant in the VCP gene or another MSP-related gene over time. Participants complete in-person and remote visits that include strength, movement, and daily-function assessments, neurological and cognitive testing, and collection of biological samples for future biomarker research. Cure VCP Disease provides travel support for participants. To learn more, contact projectcreate@med.miami.edu.
• VCP and Multisystem Proteinopathy Studies (John Walton Muscular Dystrophy Research Centre, Newcastle University) – Led by Professor Jordi Díaz-Manera, the VCP International Study gathered clinical and genetic information on people with VCP-MSP from 52 centers in 24 countries, making it one of the largest efforts to describe how the condition presents and progresses. Building on that work, the team has launched a new international study of people with multisystem proteinopathies, including VCP-MSP, to further define clinical features, family histories, and links between specific gene changes and symptoms.
• Natural History Study of Patients With VCP-related Disease (Nationwide Children’s Hospital) – This study was completed in August 2025. It was designed to evaluate the usefulness of strength, functional, and patient reported outcomes in quantifying disease progression over one year in individuals with mutations in the VCP Initial findings suggest that these outcomes and patient-reported measures can reliably track symptoms and effects on daily functioning, helping inform future studies and clinical trials.

Cure VCP Disease Patient Registry

People living with VCP-MSP and their family members are encouraged to join the Cure VCP Disease Patient Registry. Created in 2018, this international registry collects information about diagnosis, symptoms, and quality of life over time. Registry data have already supported published research on how VCP-MSP varies from person to person and how it progresses, and the registry helps researchers connect with people who may be interested in future studies and clinical trials. To learn more or enroll, visit curevcp.org/patient-registry.

MDA’s work to advance VCP-MSP research

Since its inception, MDA has invested more than $3.2 million in research on VCP-MSP. Together with support from patient advocacy organizations such as Cure VCP Disease and the National Institutes of Health (NIH), researchers have identified many of the gene variants responsible for VCP-MSP, improving diagnosis and understanding of how the condition develops. While significant challenges remain, continued research is laying the foundation for future therapies and improving care for individuals and families affected by this rare condition.

MDA’s Resource Center provides support, guidance, and resources for patients and families, including information about VCP-associated multisystem proteinopathy (VCP-MSP), open clinical trials, and other services. Contact the MDA Resource Center at 1-833-ASK-MDA1 or ResourceCenter@mdausa.org.