Multiple system atrophy requires a comprehensive approach that addresses movement difficulties, blood pressure instability, and other challenging symptoms, with doctors working to improve quality of life while researchers explore therapies that could one day slow or stop the disease’s progression.

Understanding Treatment Goals for Multiple System Atrophy

When someone receives a diagnosis of multiple system atrophy, often shortened to MSA, the focus of medical care shifts toward managing symptoms and maintaining independence for as long as possible. This rare brain condition causes nerve cells in certain parts of the brain to deteriorate over time, leading to problems with movement, balance, and automatic body functions like blood pressure control and digestion. Because MSA affects multiple body systems simultaneously, treatment must address many different symptoms at once.^[1]

The treatment approach depends heavily on which symptoms are most troublesome for each person and how quickly the disease is progressing. Some people experience more problems with movement and stiffness, similar to Parkinson’s disease, while others struggle primarily with balance and coordination. Nearly everyone with MSA develops issues with their autonomic nervous system, the part of the nervous system that controls involuntary functions like blood pressure, bladder control, and digestion. These autonomic problems often appear early and can be some of the most challenging symptoms to manage.^[2]

Medical professionals recognize that there is currently no cure for MSA and no treatment that can stop the brain cells from deteriorating. However, various medications and therapies approved by medical societies can help control specific symptoms and improve daily functioning. At the same time, researchers around the world are testing new approaches in clinical trials, hoping to discover treatments that might slow disease progression or target the underlying causes of nerve cell damage.^[3]

Because MSA affects so many different body systems, treatment works best when coordinated by a team of healthcare professionals. This typically includes neurologists who specialize in movement disorders, physical therapists, occupational therapists, speech therapists, dietitians, and other specialists who can address specific symptoms as they arise. The patient’s own priorities and goals guide which treatments receive the most attention, since what matters most varies from person to person.^[8]

Standard Treatments Available Today

Managing Movement Problems

For people whose MSA primarily causes movement difficulties similar to Parkinson’s disease, doctors often try medications that work in Parkinson’s disease. The most common is levodopa, a drug that the body converts into dopamine, a chemical messenger that helps control movement. However, levodopa helps only about 30% to 40% of people with MSA, and even when it does work, the benefit is usually modest and temporary. The drug may help with stiffness and slow movement more than with balance problems.^[7]

When levodopa is prescribed, doctors typically start with a lower dose and gradually increase it while watching for side effects. Common side effects include nausea, dizziness, confusion, and involuntary movements. Because MSA causes problems with blood pressure control, levodopa can sometimes make dizziness when standing worse, which limits how much can be used safely. Some doctors also try other Parkinson’s medications like dopamine agonists, which mimic dopamine’s effects, or anticholinergic drugs that reduce muscle stiffness, though these often provide even less benefit than levodopa.^[5]

Physical therapy plays a crucial role in maintaining mobility and preventing complications. A physical therapist can design specific exercises to maintain muscle strength, improve posture, and reduce the risk of falls. As the disease progresses, the therapist may recommend assistive devices like canes or walkers. Most people with MSA will need a walking aid within a few years after symptoms begin, so learning to use these devices safely and effectively becomes important.^[2]

Treating Blood Pressure Problems

One of the most common and troublesome symptoms in MSA is orthostatic hypotension, a sudden drop in blood pressure when standing up from sitting or lying down. This can cause severe dizziness, lightheadedness, blurred vision, weakness, or even fainting. Falls resulting from orthostatic hypotension can lead to serious injuries, making this a priority symptom to address.^[3]

Treatment for orthostatic hypotension starts with non-drug approaches. Doctors recommend increasing salt and fluid intake to expand blood volume, which helps maintain blood pressure. Wearing compression stockings on the legs can prevent blood from pooling in the lower body when standing. Elevating the head of the bed by several inches at night helps reduce overnight drops in blood pressure. Small, frequent meals rather than large ones can prevent blood pressure from dropping after eating. Physical exercises called “counter-maneuvers” like crossing the legs, squatting, or contracting leg muscles can provide quick relief when dizziness occurs.^[7]

When lifestyle measures aren’t enough, medications can help raise blood pressure. Midodrine is a drug that tightens blood vessels to increase blood pressure, typically taken several times during the day. Fludrocortisone is a hormone-like medication that helps the body retain salt and water. Droxidopa works by converting into norepinephrine, a chemical that raises blood pressure. Some doctors prescribe pyridostigmine, which can modestly improve blood pressure control with fewer side effects.^[8]

Addressing Bladder and Bowel Issues

Bladder control problems affect most people with MSA and can include urgency (sudden, strong need to urinate), frequency (needing to urinate often, including at night), and difficulty emptying the bladder completely. Medications called anticholinergics or antispasmodics, such as oxybutynin or tolterodine, can reduce urgency and frequency by relaxing the bladder muscle. However, these drugs can cause side effects like dry mouth, constipation, and confusion, particularly in older adults.^[5]

When the bladder doesn’t empty completely, the remaining urine can lead to infections. Some people need to use intermittent catheterization, where a thin tube is inserted several times a day to drain the bladder completely. A urologist can teach this technique and monitor for complications. Constipation, another common problem, is treated with increased fiber intake, adequate fluids, stool softeners, and sometimes medications that stimulate bowel movements.^[7]

Managing Speech and Swallowing Difficulties

As MSA progresses, many people develop speech problems including a soft voice, slurred speech, or a voice that sounds strained or quivering. Speech therapy can teach techniques to speak more clearly and loudly, and therapists may recommend assistive communication devices when speech becomes very difficult. Some people benefit from the Lee Silverman Voice Treatment, a specific therapy program originally developed for Parkinson’s disease that focuses on speaking louder.^[4]

Swallowing difficulties develop in many people with MSA and pose serious risks because food or liquid can enter the lungs instead of the stomach, causing pneumonia. A speech-language pathologist can evaluate swallowing function and recommend safer swallowing techniques, changes in food texture (like thickening liquids or softening solid foods), and proper positioning during meals. In advanced stages, some people may need a feeding tube to ensure adequate nutrition and prevent aspiration pneumonia.^[7]

Sleep-Related Problems

Sleep disturbances are common and often appear before other MSA symptoms. REM sleep behavior disorder causes people to physically act out their dreams, sometimes violently, which can lead to injuries. Medications like clonazepam or melatonin can reduce these behaviors and help everyone sleep more safely. Other sleep problems include fragmented sleep, restless legs syndrome, and sleep apnea, each requiring specific treatments like changes in sleep habits, medications, or breathing devices.^[4]

Treatment Duration and Adjustments

MSA treatment is ongoing and requires frequent adjustments as the disease progresses and symptoms change. Medications that were helpful initially may become less effective or cause intolerable side effects, requiring switches to different drugs. Regular follow-up appointments allow doctors to monitor disease progression, adjust treatments, and address new symptoms as they emerge. Because MSA typically progresses over 5 to 10 years, long-term planning becomes essential, including discussions about advanced care preferences and quality-of-life priorities.^[8]

Emerging Therapies in Clinical Trials

Targeting Alpha-Synuclein Accumulation

Scientists have discovered that MSA involves abnormal accumulation of a protein called alpha-synuclein in brain cells, particularly in cells called oligodendrocytes that normally support nerve cells. These abnormal protein clumps, called glial cytoplasmic inclusions, are a hallmark feature of MSA. Researchers believe that preventing this protein from clumping or removing existing clumps might slow or stop disease progression, leading to several experimental approaches now being tested.^[13]

One promising strategy involves immunotherapy, where antibodies are designed to recognize and bind to alpha-synuclein, potentially preventing it from spreading or helping the immune system clear it away. Several clinical trials are testing different antibodies that target alpha-synuclein in various ways. These trials are being conducted at specialized centers in the United States, Europe, and Asia, typically enrolling people who have been diagnosed with MSA within the past few years, since early treatment might be more effective.^[8]

These immunotherapy trials involve multiple phases. Phase I trials focus on safety, determining whether the antibody causes harmful effects and establishing safe dosing. Phase II trials examine whether the treatment shows signs of slowing disease progression, often by measuring changes in movement, balance, and autonomic function over several months. Phase III trials compare the new treatment to placebo in larger groups of patients to definitively determine effectiveness. Early results from some trials have shown that these antibodies can be administered safely, though proving they slow disease progression requires longer observation periods.^[13]

Cell-Based Therapies

Another experimental approach involves using stem cells or other cell types to potentially replace damaged brain cells or protect remaining cells from further damage. Several types of cells are being explored, including mesenchymal stem cells derived from sources like bone marrow or umbilical cord blood. The theory is that these cells might release protective factors that reduce inflammation in the brain or support the survival of threatened nerve cells.^[11]

Some research centers have tested injecting human umbilical cord blood-mononuclear cells directly into the space around the brain and spinal cord through specialized procedures. Early reports from small groups of patients have described improvements in some symptoms and positive safety profiles, meaning serious complications were rare. However, these are preliminary findings from small studies, and larger, more rigorous trials are needed to determine whether cell-based therapies truly provide meaningful benefits.^[11]

The mechanism by which these cell therapies might work is still being studied. The cells likely don’t permanently replace damaged brain tissue but instead may reduce neuroinflammation, a harmful inflammatory process in the brain that contributes to nerve cell death. They might also release growth factors that help remaining brain cells survive longer. Clinical trials testing these approaches are generally in early phases, focusing primarily on safety and optimal delivery methods.^[8]

Neuroprotective Approaches

Researchers are investigating various medications and compounds that might protect nerve cells from the damage that occurs in MSA. One area of interest involves reducing oxidative stress and inflammation in the brain, processes that contribute to nerve cell death. Various antioxidants and anti-inflammatory agents are being studied, though none have yet proven definitively effective in large clinical trials.^[13]

Some trials are exploring repurposing existing drugs approved for other conditions. For example, certain drugs that affect immune function or cellular energy production are being tested to see if they might slow MSA progression. The advantage of repurposing existing drugs is that their safety profiles are already well-established, potentially speeding the path to approval if they prove effective.^[8]

Novel Drug Mechanisms

Beyond immunotherapy and cell therapy, scientists are testing drugs that work through entirely different mechanisms. Some experimental treatments aim to enhance the ability of oligodendrocytes (the brain cells primarily affected in MSA) to clear out abnormal protein accumulations. Others try to reduce the production of alpha-synuclein or prevent it from folding into the abnormal shapes that cause problems.^[13]

Researchers are also investigating compounds that might reduce the toxic effects that occur when oligodendrocytes fail to properly support nearby nerve cells. This involves complex molecular pathways including neurotrophic factors (proteins that support nerve cell survival) and pathways that regulate cellular stress responses. While these approaches show promise in laboratory studies, translating them into effective human treatments remains challenging.^[8]

Eligibility and Access to Clinical Trials

Clinical trials for MSA typically have specific eligibility requirements. Most seek people who have been diagnosed with MSA relatively recently, often within the past two to five years, because treatments might be more effective when started earlier in the disease course. Trials may specify whether they’re enrolling people with the parkinsonian type (MSA-P) or cerebellar type (MSA-C), or both. Other factors like age, disease severity, and other medical conditions affect eligibility.^[8]

Trials are being conducted at various locations worldwide, including specialized centers in the United States, Canada, European countries, Japan, and other nations. Some trials require frequent visits to the study site, which can pose challenges for people who live far away. Researchers are increasingly recognizing these barriers and working to make participation more feasible, including through remote assessments when possible.^[13]

Most Common Treatment Methods

• Medication for Movement Symptoms
  • Levodopa to increase dopamine and potentially reduce stiffness and slow movement, though benefit is limited and temporary in MSA
  • Dopamine agonists as alternative medications that mimic dopamine effects
  • Anticholinergic drugs to help reduce muscle rigidity
• Blood Pressure Management
  • Midodrine to tighten blood vessels and raise blood pressure when standing
  • Fludrocortisone to help retain salt and water in the body
  • Droxidopa that converts to norepinephrine to increase blood pressure
  • Pyridostigmine for modest blood pressure improvements with fewer side effects
  • Non-drug approaches including increased salt and fluid intake, compression stockings, and elevated sleeping position
• Bladder Control Medications
  • Anticholinergic drugs such as oxybutynin or tolterodine to reduce urgency and frequency
  • Intermittent catheterization when the bladder doesn’t empty completely
• Rehabilitation Therapies
  • Physical therapy to maintain strength, improve balance, prevent falls, and learn to use assistive devices
  • Occupational therapy to help with daily activities and recommend home modifications
  • Speech therapy to address voice problems and swallowing difficulties
• Sleep Disorder Treatment
  • Clonazepam or melatonin for REM sleep behavior disorder
  • Breathing devices for sleep apnea
  • Medications for restless legs syndrome
• Experimental Immunotherapy (Clinical Trials)
  • Antibodies targeting alpha-synuclein to potentially prevent protein accumulation or enhance clearance
  • Multiple trial phases testing safety and effectiveness
• Stem Cell Therapies (Clinical Trials)
  • Mesenchymal stem cells to potentially protect nerve cells or reduce brain inflammation
  • Human umbilical cord blood-mononuclear cell injections into the space around the brain and spinal cord
  • Early research showing positive safety profiles in small patient groups
• Neuroprotective Approaches (Clinical Trials)
  • Compounds aiming to reduce oxidative stress and inflammation in the brain
  • Repurposed drugs originally approved for other conditions
  • Experimental medications affecting various molecular pathways involved in nerve cell survival