Progressive multiple sclerosis is a form of the disease where symptoms steadily worsen over time, making everyday activities gradually more challenging. While there is no cure, modern treatments can slow down the progression and help people maintain their quality of life.

Understanding Treatment Goals in Progressive MS

When someone receives a diagnosis of progressive multiple sclerosis, the focus of care shifts toward managing a condition that steadily advances rather than coming and going in waves. Unlike the more common relapsing-remitting form, progressive MS involves continuous accumulation of disability, which requires a different approach to treatment. The main goals are to slow down how quickly the disease worsens, manage symptoms that interfere with daily life, and help people maintain their independence for as long as possible.^[1][3]

Treatment plans for progressive MS depend heavily on the specific type someone has been diagnosed with, whether primary progressive or secondary progressive, as well as how advanced their symptoms are and their overall health. What works well for one person may not be suitable for another. Medical societies have approved certain standard treatments based on research, and at the same time, scientists continue to explore new therapies through clinical trials that may offer additional hope for people living with this challenging condition.^[8][11]

The disease affects the central nervous system by causing both inflammation and a process called neurodegeneration, which means nerve cells in the brain and spinal cord gradually lose their ability to function properly. This dual nature of progressive MS explains why treatment needs to address both the immune system’s attacks on healthy tissue and the ongoing damage to nerve cells themselves.^[1][3]

Standard Treatment Approaches

For many years, finding effective medications for progressive multiple sclerosis proved extremely difficult. The vast majority of drugs tested in clinical trials showed disappointing results, which researchers believe happened because progressive MS has different underlying mechanisms compared to relapsing-remitting disease. The inflammation that drives relapses is less prominent in progressive forms, while nerve damage becomes the dominant factor.^[3][11]

Currently, only two medications have received approval from the U.S. Food and Drug Administration specifically for treating progressive MS. The first is ocrelizumab, marketed as Ocrevus, which is approved for primary progressive multiple sclerosis. This medication is a monoclonal antibody therapy, meaning it’s a specially designed protein that targets specific cells in the immune system. Ocrelizumab works by attaching to certain immune cells called B cells and removing them from circulation. These B cells contribute to the inflammation and damage seen in MS.^[13]

Ocrelizumab is given through an infusion into a vein, typically administered twice per year. In 2024, a newer version became available that can be given as an injection under the skin, called Ocrevus Zunovo, providing patients with another delivery option that may be more convenient. The medication has been shown in clinical trials to slow the worsening of disability in people with primary progressive MS, though it does not stop progression entirely or reverse damage that has already occurred.^[13]

Treatment duration with disease-modifying therapies like ocrelizumab is typically ongoing, as stopping the medication may allow disease activity to resume. Healthcare providers monitor patients regularly through neurological examinations and MRI scans to assess whether the treatment is providing benefit and to watch for any concerning side effects.^[10][14]

Beyond disease-modifying drugs that aim to slow progression, a substantial portion of MS treatment involves managing individual symptoms that affect daily life. These symptoms can include muscle stiffness, which doctors call spasticity, bladder control problems, fatigue, pain, difficulty walking, and changes in thinking or memory. Each of these symptoms can be addressed with specific medications or therapies.^[1][10]

For muscle stiffness and spasms, healthcare providers may prescribe muscle relaxant medications such as baclofen or tizanidine. These work by affecting nerve signals in the spinal cord that control muscle tension. Physical therapy is also extremely valuable for maintaining mobility and strength, teaching people exercises and stretches that can reduce stiffness and improve coordination.^[15]

When someone experiences an acute worsening of symptoms, doctors may use high-dose corticosteroids such as methylprednisolone to reduce inflammation quickly. These powerful anti-inflammatory drugs are typically given through an IV infusion over several days. While corticosteroids can help with flare-ups, they are not used for long-term management because of significant side effects that can develop with prolonged use, including bone thinning, increased blood sugar, and higher infection risk.^[15]

Bladder problems affect many people with progressive MS and can significantly impact quality of life. Medications such as oxybutynin or tolterodine can help reduce urinary urgency and frequency by relaxing the bladder muscle. In some cases, people may need to learn to use a catheter to empty the bladder completely if nerve damage has made this difficult. Healthcare providers can teach proper techniques to minimize the risk of urinary tract infections.^[1]

Fatigue is one of the most common and troublesome symptoms in progressive MS. While medications like amantadine or modafinil are sometimes prescribed to boost energy levels, their effectiveness varies from person to person. Often, managing fatigue requires a combination of medication, energy conservation techniques, regular exercise, and ensuring good sleep habits. Occupational therapists can help people learn to organize their daily activities to preserve energy for the most important tasks.^[16][17]

Innovative Treatments Being Tested in Clinical Trials

Because effective treatments for progressive MS remain limited, researchers around the world are actively testing new approaches in clinical trials. These studies are exploring medications and therapies that work through different mechanisms than currently available treatments, with the hope of finding better ways to protect nerve cells from damage or even help them repair themselves.^[11]

Many of the experimental treatments being evaluated fall into the category of agents with what researchers call neuroprotective effects. This means they aim to shield nerve cells and their protective coverings from the ongoing damage that characterizes progressive MS. Some of these approaches try to reduce harmful inflammation that occurs within the brain and spinal cord itself, while others attempt to support the survival and function of nerve cells directly.^[11]

Several trials have investigated whether existing immunosuppressant medications, which are drugs that broadly suppress immune system activity, might benefit people with progressive MS. While most of these studies had disappointing outcomes, they provided valuable lessons. Scientists learned that the pathways driving progression may be quite distinct from those causing relapses, which explains why treatments effective for relapsing-remitting MS often don’t work for progressive forms.^[3][11]

One area of intense research interest involves medications that target specific aspects of inflammation that occur inside the central nervous system, rather than just in the bloodstream. Researchers have noted that in progressive MS, immune cells and inflammatory processes become trapped behind the blood-brain barrier, continuing to cause damage in a way that may not respond to treatments targeting the peripheral immune system. New therapies are being designed to penetrate into the brain and spinal cord to address this compartmentalized inflammation.^[3]

Another promising avenue involves therapies aimed at helping the brain’s support cells, called oligodendrocytes, survive longer or even regenerate. These cells produce myelin, the protective covering around nerve fibers that gets destroyed in MS. If treatments could encourage myelin repair, theoretically they might help restore some lost function. Several molecules that promote oligodendrocyte survival or maturation are being studied in early-phase trials.^[3]

Some clinical trials are investigating whether existing medications used for other conditions might have unexpected benefits in progressive MS. This approach, called drug repurposing, can potentially bring new treatments to patients faster since these medications already have known safety profiles. Examples include certain cholesterol-lowering drugs, diabetes medications, and even some antibiotics that researchers believe might have properties that protect nerve cells beyond their original intended use.^[11]

The phases of clinical trials serve different purposes in determining whether a new treatment is safe and effective. Phase I trials primarily assess safety, testing a new medication in a small group of volunteers to understand how the body processes it and what side effects might occur. Phase II trials involve larger groups of patients and focus on whether the treatment shows signs of working against the disease, while also continuing to monitor for side effects. Phase III trials are the largest studies, comparing the new treatment directly against either a placebo or the current standard treatment to definitively prove whether it provides meaningful benefit.^[11]

One challenge in conducting trials for progressive MS is selecting appropriate ways to measure whether a treatment is working. Traditional measures like counting relapses don’t apply since progression happens gradually without distinct attacks. Researchers have developed composite endpoints that combine multiple measurements, such as walking speed over a set distance, hand coordination tests using pegs, and cognitive assessments. They also use advanced MRI techniques to measure brain shrinkage, which correlates with worsening disability. Some newer trials are measuring levels of neurofilament light chain in blood or spinal fluid, which is a protein released when nerve cells are damaged and serves as a marker of disease activity.^[11]

While most experimental therapies are still being studied and their effectiveness remains unproven, preliminary results from some trials have shown encouraging signs. For instance, certain studies have reported slowing of brain volume loss or modest improvements in mobility measures. However, these early findings need confirmation in larger studies before the treatments can be approved for general use. The path from laboratory discovery to approved medication typically takes many years and requires extensive testing to ensure both safety and effectiveness.^[11]

Most common treatment methods

• Disease-modifying therapy
  • Ocrelizumab (Ocrevus), a monoclonal antibody that targets B cells in the immune system, given as an infusion twice yearly or as a subcutaneous injection
  • Aims to slow the progression of disability by reducing inflammation and preventing new damage to the nervous system
  • Requires ongoing monitoring for potential side effects, particularly infections
• Symptom management medications
  • Muscle relaxants such as baclofen or tizanidine for spasticity and muscle stiffness
  • Bladder control medications like oxybutynin or tolterodine for urinary urgency and frequency
  • Fatigue-reducing medications such as amantadine or modafinil, though effectiveness varies
  • High-dose corticosteroids like methylprednisolone for acute symptom flare-ups
• Physical and occupational therapy
  • Exercise programs designed to maintain mobility, strength, and balance
  • Stretching routines to reduce muscle stiffness and prevent contractures
  • Energy conservation techniques to manage fatigue and maintain independence
  • Training in the use of assistive devices like canes, walkers, or wheelchairs when needed
• Experimental neuroprotective agents
  • Medications being tested in clinical trials that aim to protect nerve cells from damage
  • Therapies designed to reduce inflammation specifically within the brain and spinal cord
  • Compounds that may promote myelin repair or support oligodendrocyte survival
  • Repurposed drugs from other medical conditions that might have unexpected benefits in progressive MS