Most current medications and treatments are focused on relapsing MS and not on primary progressive MS (PPMS). However, clinical trials are constantly being held to help better understand PPMS and to find new, effective treatments.
The four main types of MS are:
- clinically isolated syndrome (CIS)
- relapsing-remitting MS (RRMS)
- primary progressive MS (PPMS)
- secondary progressive MS (SPMS)
These MS types were created to help medical researchers categorize clinical trial participants with similar disease development. These groupings allow researchers to evaluate the effectiveness and safety of certain treatments without using a large number of participants.
Only 15 percent or so of all people diagnosed with MS have PPMS. PPMS affects men and women equally, while RRMS is much more common in women than in men.
Most types of MS occur when the immune system attacks the myelin sheath. The myelin sheath is a fatty, protective substance that surrounds nerves in the spinal cord and brain. When this substance is attacked, it causes inflammation.
PPMS leads to nerve damage and scar tissue on the damaged areas. The disease disturbs the process of nerve communication, causing an unpredictable pattern of symptoms and disease progression.
Unlike people with RRMS, people with PPMS experience gradually worsening function without early relapses or remissions. In addition to a gradual increase in disability, people with PPMS may also experience the following symptoms:
Treating PPMS is more difficult than treating RRMS, and it includes the use of immunosuppressive therapies. These therapies offer only temporary help. They can only be safely and continuously used for a few months to a year at a time.
While the Food and Drug Administration (FDA) has approved many medications for RRMS, not all are appropriate for progressive types of MS. RRMS medications, which are also known as disease-modifying drugs (DMDs), are taken continuously and often have intolerable side effects.
Actively demyelinating lesions and nerve damage can also be found in people with PPMS. The lesions are highly inflammatory and may cause damage to the myelin sheath. It’s currently unclear whether medications that reduce inflammation can slow progressive forms of MS.
The FDA approved Ocrevus (ocrelizumab) as a treatment for both RRMS and PPMS in March 2017. To date, it’s the only drug that’s been FDA-approved to treat PPMS.
Clinical trials indicated that it was able to slow the progression of symptoms in PPMS by around 25 percent when compared to a placebo.
Ocrevus is also approved for the treatment of RRMS and “early” PPMS in England. It’s not yet approved in other parts of the United Kingdom.
The National Institute for Health Excellence (NICE) initially rejected Ocrevus on the grounds that the cost of providing it outweighed its benefits. However, NICE, the National Health Service (NHS), and the drug manufacturer (Roche) eventually renegotiated its price.
A key priority for researchers is learning more about progressive forms of MS. New drugs must go through rigorous clinical testing before the FDA approves them.
Most clinical trials last for 2 to 3 years. However, because the research is limited, even longer trials are needed for PPMS. More RRMS trials are being conducted because it’s easier to judge the medication’s effectiveness on the relapses.
See the National Multiple Sclerosis Society website for a complete list of clinical trials in the United States.
The following select trials are currently underway.
NurOwn stem cell therapy
Brainstorm Cell Therapeutics is performing a phase II clinical trial to investigate the safety and effectiveness of NurOwn cells in the treatment of progressive MS. This treatment uses stem cells derived from participants that have been stimulated to produce specific growth factors.
In November 2019, the National Multiple Sclerosis Society awarded Brainstorm Cell Therapeutics a $495,330 research grant in support of this treatment.
The trial is expected to conclude in September 2020.
MedDay Pharmaceuticals SA is currently performing a phase III clinical trial on the effectiveness of a high-dose biotin capsule in treating people with progressive MS. The trial also aims to specifically focus on individuals with gait problems.
Biotin is a vitamin that’s involved in influencing cellular growth factors as well as myelin production. The biotin capsule is being compared to a placebo.
The trial is no longer recruiting new participants, but it’s not expected to conclude until June 2023.
AB Science is performing a phase III clinical trial on the drug masitinib. Masitinib is a drug that blocks the inflammation response. This leads to a lower immune response and lower levels of inflammation.
The trial is assessing the safety and effectiveness of masitinib when compared to a placebo. Two masitinib treatment regimens are being compared to the placebo: The first regimen uses the same dosage throughout, while the other involves dosage escalation after 3 months.
The trial is no longer recruiting new participants. It’s expected to conclude in September 2020.
The following trials have recently been completed. For most of them, the initial or final results have been published.
MediciNova has completed a phase II clinical trial on the drug ibudilast. Its aim was to determine the safety and activity of the drug in people with progressive MS. In this study, ibudilast was compared to a placebo.
Initial study results indicate that ibudilast slowed the progression of brain atrophy when compared to the placebo over a 96-week period. The most common side effects reported were gastrointestinal symptoms.
Although results are promising, additional trials are needed to see if the results of this trial can be reproduced and how ibudilast may compare to Ocrevus and other drugs.
The National Institute of Allergy and Infectious Diseases (NIAID) recently completed a phase I/II clinical trial to evaluate the effect of idebenone on people with PPMS. Idebenone is a synthetic version of coenzyme Q10. It’s believed to limit damage to the nervous system.
Throughout the course of the last 2 years of this 3-year trial, participants took either the drug or a placebo. Preliminary results indicated that, over the course of the study, idebenone provided no benefit over the placebo.
Teva Pharmaceutical Industries sponsored a phase II study in an effort to establish a proof of concept for treating PPMS with laquinimod.
It isn’t fully understood how laquinimod works. It’s believed to change the behavior of immune cells, therefore preventing nervous system damage.
Disappointing trial results have led its manufacturer, Active Biotech, to discontinue the development of laquinimod as a drug for MS.
In 2018, University College Dublin completed a phase IV trial to examine the effect of fampridine in people with upper limb dysfunction and either PPMS or SPMS. Fampridine is also known as dalfampridine.
Although this trial has been completed, no results have been reported.
However, according to a 2019 Italian study, the drug may improve information processing speed in people with MS. A 2019 review and meta-analysis concluded that there was strong evidence the drug improved the ability of people with MS to walk short distances as well as their perceived walking capacity.
The National Multiple Sclerosis Society is promoting ongoing research into progressive types of MS. The goal is to create successful treatments.
Some research has focused on the difference between people with PPMS and healthy individuals. A recent study found that stem cells in the brains of people with PPMS look older than the same stem cells in healthy people of a similar age.
Additionally, the researchers found that when oligodendrocytes, the cells that produce myelin, were exposed to these stem cells, they expressed different proteins than in healthy individuals. When this protein expression was blocked, the oligodendrocytes behaved normally. This could help explain why the myelin is compromised in people with PPMS.
Another study found that people with progressive MS had lower levels of molecules called bile acids. Bile acids have multiple functions, particularly in digestion. They also have an anti-inflammatory effect on some cells.
Receptors for bile acids were also found on cells in MS tissue. It’s thought that supplementation with bile acids may benefit people with progressive MS. In fact, a clinical trial to test exactly this is currently underway.
Hospitals, universities, and other organizations all over the United States are continuously working to learn more about PPMS and MS in general.
So far only one drug, Ocrevus, is approved by the FDA for treatment of PPMS. While Ocrevus slows down the progression of PPMS, it doesn’t stop the progression.
Some drugs, such as ibudilast, appear promising based on early trials. Other drugs, such as idebenone and laquinimod, haven’t been shown to be effective.
Additional trials are needed to identify additional therapies for PPMS. Ask your healthcare provider about the latest clinical trials and research that could benefit you.