Multiple System Atrophy: Understanding the Condition

Have you or someone you know been diagnosed with Multiple System Atrophy (MSA)?

Multiple System Atrophy is a rare but serious neurodegenerative condition, affecting an estimated 2 to 5 people per 100,000 worldwide. ^{​1, 2​} It can impact movement, balance, blood pressure, digestion, and more—often progressing rapidly over the course of 5 to 10 years. ​³​

This blog provides a comprehensive overview of Multiple System Atrophy, including its definition, diagnostic criteria, key symptoms, therapeutic options for daily management, and an overview of the current scientific research in development . Whether you are affected by Multiple System Atrophy or supporting an individual with this condition, this blog aims to inform and empower your understanding throughout your journey.

What is Multiple System Atrophy?

Multiple System Atrophy (MSA) is a rare, progressive neurodegenerative disorder that causes nerve cells to deteriorate in several key areas of the brain. These areas control movement, balance, coordination, and involuntary functions such as blood pressure regulation, digestion, and breathing. As the disease progresses and more nerve cells are lost, it becomes increasingly difficult for the body to carry out these functions normally.^{1,  3}​^{, 4​}

There are two main types of Multiple System Atrophy, based on the main symptoms a person experiences, especially early in the disease course. The first type is MSA-P (Parkinsonian type) which involves symptoms similar to Parkinson’s disease, such as slowness of movement, stiffness, and tremor. The second is MSA-C (Cerebellar type), which primarily affects balance and coordination, due to damage in the cerebellum—the part of the brain that helps control these functions. ​^{1,  3}​^{, 4​}

Multiple System Atrophy is a rare condition, estimated to affect between 2 and 5 people per 100,000 worldwide.​^{1, 2​} ​ In the United States, it is thought to impact approximately 15,000 to 50,000 individuals across all racial groups.​³

What causes Multiple System Atrophy?

The exact cause of Multiple System Atrophy is still unknown. However, researchers have identified several biological factors that may play a role in its development: ​^{3, 5}​

• Alpha-synuclein (α-synuclein): α-Synuclein is a protein naturally found in the brain that is believed to help nerve cells communicate.​^{5, 6}  In Multiple System Atrophy, this protein builds ups and forms clumps in different nerve cells, including those that create the myelin sheath — the protective layer surrounding the nerves.​​^{3, 5, 7}​ These cells become damaged by the buildup of alpha-synuclein and can no longer maintain the myelin sheath around the neurons. Without this protective covering, nerve fibers become exposed, slowing down or blocking the signals being transmitted within them — similar to a frayed wire that can’t carry electricity properly. ​^{5, 7}​^{, 8, 9} 
• Mitochondrial dysfunction: Mitochondria are tiny structures in cells that produce energy. They become damaged in Multiple System Atrophy, which can lead to reduced energy availability and an increased production of toxic byproducts. This can cause brain cells to become damaged, contributing to the progression of the disease. ​^{5, 7}​^{, 10} 
• Neuroinflammation: In Multiple System Atrophy, the body’s immune response may become overactive, leading to chronic inflammation in the brain. While it’s not yet clear whether this inflammation is a cause or a consequence of the disease, it can contribute to the progression of Multiple System Atrophy by damaging brain cells and tissues ​^{5, 7}​^{, 11​}
• Impaired protein degradation: The brain has systems that normally clean up damaged or excess proteins. In Multiple System Atrophy, these systems don’t work effectively, allowing toxic proteins to accumulate. Over time, this buildup can interfere with how cells function and contribute to cell death. ​^{5, 7}​

Risk Factors for Multiple System Atrophy

The risk factors for Multiple System Atrophy are not fully understood, but research suggests that several elements may contribute to its development:

• Age: Multiple System Atrophy usually begins in adults over the age of 30, with symptoms most commonly starting between the ages of 50 and 60. It affects both men and women equally. ^1,​ ^{9, 12​, 13} ​
• Genetic factors: Most cases of Multiple System Atrophy are classified as sporadic, meaning they appear randomly without a clear genetic cause or family history. However, in about 2–7% of cases, a genetic component may be involved, with certain mutations increasing the likelihood of developing the condition. ​¹⁰ These include mutations in genes involved in a-synuclein production (e.g., SNCA), mitochondrial function (e.g., COQ2), cell regulation (e.g., LRRK2), fat metabolism (e.g., GBA), and inflammation control (e.g., TNF-ɑ or IL-1α). Mutations in some of these genes have also been associated with Parkinson’s disease.^{5, 7}​^{, 10, 14}
• Environmental factors: Exposure to certain environmental agents— such as organic solvents, plastic monomers/additives, pesticides, agricultural activities, metals and tobacco — have been associated with Multiple System Atrophy in some studies. However, the exact mechanisms remain unclear and require further research.​ ^{10 , 14}​

What are the Symptoms of Multiple System Atrophy?

People with Multiple System Atrophy typically experience a combination of symptoms affecting autonomic functions—those that usually happen without thinking— movement, and sometimes cognitive or emotional.

Most people experience issues with automatic body functions first, months or even years before movement problems. ^{1, 3}​^{, 15, 16}​ Common examples include:

• Low blood pressure when standing up from a sitting or lying position (orthostatic hypotension), which can cause dizziness, lightheadedness, or fainting.​^{1, 3}​^{, 15, 16}
• Bladder problems, such as frequent or urgent need to urinate, difficulty emptying the bladder, or accidental leakage (urinary incontinence). ​^{1, 3}​^{, 15, 16}
• Bowel issues, such as constipation or trouble controlling the bowels (bowel incontinence). ​​^{1, 3}​^{, 15, 16}
• Sexual dysfunction, including erectile dysfunction in men and reduced sexual function overall. ​​^{1, 3}​^{, 15, 16}
• Sleep disturbances, such as REM sleep behavior disorder (acting out dreams unknowingly whilst asleep) and sleep apnea (interrupted breathing during sleep). ​​^{1, 3}​^{, 15, 16}
• Decreased ability to sweat or trouble regulating body temperature, which can cause a feeling of unusual heat or cold. ^{1, 3}​^{, 15, 16}

Symptoms affecting movement differ depending on the type of Multiple System Atrophy a person has:

• Parkinsonian type MSA (MSA-P) includes symptoms similar to Parkinson’s disease, such as muscle stiffness or rigidity, slow movement, tremors, slurred speech and poor balance. ​​^{1, 3}​^{, 15, 16}
• Cerebellar type MSA (MSA-C) is characterized by problems with coordination and balance (ataxia), trouble with swallowing, speech difficulties or a shaky voice, and unusual eye movements. ​​^{1, 3}​^{, 15, 16}​

Some people may also experience cognitive and emotional symptoms such as trouble controlling emotions, anxiety, depression, or panic attacks. ​​^{1, 3}​^{, 15, 16}

Diagnosis of Multiple System Atrophy

Diagnosing Multiple System Atrophy can be especially difficult in the early stages, as many of its symptoms—like muscle stiffness, balance issues, and slowed movement—closely resemble those of other neurological conditions, particularly Parkinson’s disease. ​^{1, 3​, 15}​ There’s no single test that can confirm Multiple System Atrophy. Instead, physicians use a combination of tools to support the diagnosis and rule out other possible causes. ​^{1, 3, 15}

The diagnostic process typically starts with a review of the individual’s medical and family history, followed by a physical and neurological examination to assess muscle tone, coordination, reflexes, and involuntary (autonomic) functions.

To evaluate autonomic functions, a physician may order tests to evaluate blood pressure, bladder and bowel functions, heart rhythm (electrocardiogram) and the body’s ability to regulate temperature through a sweat test. If the person shows signs of sleep disturbance—such as snoring, acting out dreams, or pauses in breathing during sleep—a sleep study may be recommended to assess conditions like REM sleep behavior disorder or sleep apnea. ​​^{1, 3, 15}

Brain imaging can also help support the diagnosis. An MRI (Magnetic Resonance Imaging) may show deterioration or changes in brain areas affected by Multiple System Atrophy. A PET (Positron Emission Tomography) scan, which shows how the brain uses energy, may reveal reduced activity in those same regions. ​​^{1, 3, 15, 17}

Lastly, a person’s response to Parkinson’s medications, such as levodopa, can provide important diagnostic clues. In many cases of Multiple System Atrophy, these medications offer little or no lasting benefit, helping to distinguish the condition from Parkinson’s disease. ​^{1, 3, 15}

Treatment of Multiple System Atrophy

Currently, there is no cure for Multiple System Atrophy. However, various therapies can help manage symptoms and improve quality of life. ​^{3, 15 , 18}

Medications or medical procedures

Physicians often prescribe medications or medical procedures to address specific symptoms:

• Low blood pressure (orthostatic hypotension): To prevent dizziness or fainting, physicians may prescribe medications like fludrocortisone or midodrine, which help control blood pressure.​^{3, 15, 18}
• Erectile Dysfunction: Medications like Viagra may be prescribed for individuals experiencing erectile difficulties. ​^{3, 15, 18}
• Bladder issues: In earlier stages, medications such as anticholinergics can help reduce urgency or incontinence. As the condition progresses, individuals may require catheterization to help empty the bladder. ​^{3, 15, 18}
• Movement symptoms: Medications commonly used for Parkinson’s disease—such as levodopa—may offer some relief for stiffness or slowness in a few people, particularly those with the MSA-P subtype. However, even when they do help, the benefits are often limited and may not last ​[long. ^1,, [15], [18]​
• Swallowing difficulties: Dietary changes like soft foods or thickened liquids may be recommended to prevent choking and ensure proper nutrition. In more advanced cases, a feeding tube might be necessary. ​^{3, 15, 18}
• Breathing problems: Conditions such as sleep apnea may be managed with devices that help keep airways open during sleep. In severe cases, tracheostomy may be considered to bypass upper airway obstruction. ​^{3, 15, 18}

Supportive therapies

Rehabilitation therapies can play an important role in managing Multiple System Atrophy.

Physical therapy can help preserve mobility, reduce stiffness, and prevent contractures, while occupational therapy can support daily living by helping people adapt to challenges in dressing, eating, and maintaining independence. Mobility aids such as walkers or wheelchairs may be recommended. Speech-language therapy can help with speech clarity and teach safer swallowing techniques. ​^{3, 15, 18}

Investigational Therapies for Multiple System Atrophy

Different types of investigational treatments are being studied in Multiple System Atrophy clinical trials and preclinical studies to explore their potential to slow or prevent disease progression.

Current investigational studies focus on targeting core features of the condition, including: ​[7], [19]​

1. Development in α-synuclein targeting therapy

Researches are exploring investigational therapies aimed at reducing the formation of α-synuclein clumps or to better break them down. Some strategies include:

• Immunotherapy: This treatment works by stimulating or suppressing the body’s immune response to fight disease. One approach being studied in Multiple System Atrophy involves using antibodies—proteins naturally made by the immune system—that are modified in the lab to target and eliminate the clumps of α-synuclein specifically. ​^7, ​^{18, 19}​
• Antisense oligonucleotides (ASOs): These are tiny pieces of genetic material that act like instructions to “turn down” the production of a-synuclein in the brain. Instead of removing the protein after it builds up, ASOs aim to reduce how much of it is made in the first place. ​​^7, ​^{18, 19}
• Small molecules: These are simple chemical compounds that can easily enter the body’s cells due to their size, making them versatile tools for targeting various biological processes. In Multiple System Atrophy, they are being developed to reduce the buildup of toxic a-synuclein. These therapies are being investigated to understand if they can work in different ways, such as binding to a-synuclein to prevent clumping, breaking apart existing clumps, or interfering with the processes that lead to its accumulation. ​​^7,  ​^{18, 19}

2. Neuroinflammation

In Multiple System Atrophy, the brain’s immune system can become overactive, leading to chronic inflammation that may worsen the condition. Scientists aim to develop treatments that help control inflammation in different ways, such as reducing the activity of overactive immune cells or blocking the chemical signals that amplify inflammation. ​^7,  ​^{18, 19}

3. Protein recycling

The brain’s natural systems for managing and clearing out damaged proteins often don’t work properly in Multiple System Atrophy, allowing harmful proteins like a-synuclein to build up. Investigational therapies are being studied to understand whether the brain’s natural recycling processes can be augmented—either by enhancing these mechanisms or by directing harmful proteins to cellular “disposal units” for elimination. ​^7,  ​^{18, 19}

4. Neuroprotection

Neuroprotective treatments aim to help nerve cells survive longer by targeting different aspects of the disease. Some of these investigational drugs work by aiming to balance harmful brain chemicals, like glutamate, which can become too active in Multiple System Atrophy and contribute to cell damage. Others focus on supporting the brain’s energy production— which is often reduced due to problems with mitochondria—using compounds like Coenzyme Q10. Additional strategies involve boosting the brain’s natural repair systems through neurotrophic factors, which are substances the brain makes to support nerve survival. Researchers are also studying certain types of stem cells that may release protective chemicals that support brain health. ​^7,  ​^{18, 19}

Conclusions

Multiple System Atrophy is a neurodegenerative disorder caused by the deterioration of nerve cells in several key areas of the brain. This leads to progressive problems with movement, balance, coordination, and automatic functions such as blood pressure regulation, digestion, and breathing. While there is no cure, various treatments can help manage symptoms. These may include medications for Parkinson’s-like symptoms (such as stiffness and slowness), low blood pressure, bladder issues, and sleep problems. Rehabilitation therapies—such as physical, occupational, and speech therapy—can also support daily function and quality of life. Several investigational treatments are currently being evaluated in clinical trials to explore whether and how they can target key features of the disease, including α-synuclein buildup, chronic inflammation, impaired protein recycling, and nerve cell loss.

At myTomorrows, we have a team of Patient Navigators, who are multi-lingual professionals with a medical background, who can help you to explore your treatment options and support you through your journey.

References

Authors:

Andrea Enguita Marruedo, PhD – Expert Medical Writer
Medical Content Writer at myTomorrows

Dr. Andrea Enguita Marruedo holds a master’s in Genetics and Cell Biology from the Autonomous University of Madrid and a PhD in Developmental Biology from the Erasmus Medical Centre in Rotterdam. She began her career in medical writing after completing her doctoral studies and has covered a wide range of therapeutic areas, including neuromuscular and neurodegenerative disorders, cancer, and diabetes.

Andrea specializes in translating complex biomedical topics into clear, accessible content for patients and healthcare professionals. With a strong research background and a passion for science communication, she is committed to delivering accurate, well-referenced content that supports greater awareness and understanding of medical topics among patients, caregivers, and clinicians.