Lack of Progressive MS Treatments Has Several Causes, But Advances are Promising, Reviewers Contend

Lack of Progressive MS Treatments Has Several Causes, But Advances are Promising, Reviewers Contend

The complexity in underlying mechanisms, a lack of representative research models, and inconsistent criteria defining therapeutic benefit are the main reasons why an effective therapy for progressive forms of multiple sclerosis (MS) is still lacking, researchers maintain in a review study.

Nevertheless, as research continues to shed light on the root causes of the disease, scientists will move closer to finding targeted, effective treatments, the authors say.

The article, “Progressive multiple sclerosis: from pathophysiology to therapeutic strategies,” was published in the journal Nature Reviews Drug Discovery.

Although progress has been made in developing new therapies for relapsing-remitting MS (RRMS), treatment of progressive forms of MS — characterized by gradual accumulation of disability — without acute flares (relapses) or remissions, remains unsatisfactory.

Some patients experience progressive disease from the beginning of symptoms, referred to as primary progressive MS (PPMS), while others experience it as a later stage following RRMS, in which case it is called secondary progressive MS (SPMS).

In the review study, an international team of researchers, including doctors at St. Josef-Hospital, University Hospital at Ruhr-Universität Bochum (RUB), in Germany, and collaborators at the University of Calgary and the University of Alberta, Canada, joined to discuss how much is known about the mechanisms underlying progressive MS, and the potential treatments being explored. The setbacks encountered and future challenges also were discussed.

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Emerging therapies in MS currently include those targeting inflammation and nerve cell death (neurodegeneration), as well as those promoting remyelination — that is, the repair of myelin, which is the fatty coating that surrounds and insulates nerve cells, and is destroyed in MS.

“A bottom line of our analysis is that the reason why it is so difficult to treat progressive MS is the fact that progression is caused by various mechanisms,” Simon Faissner, MD, said in a RUB press release written by Julia Weiler. Faissner is a professor at RUB and the study’s lead author.

According to the team, finding therapies for progressive MS remains an unmet need due to the complexity of mechanisms involved. Several disturbances converge: chronic inflammation with activation of microglia (specialized immune cells of the brain and spinal cord), and involvement of immune T-cells and B-cells; in turn, inflammation can lead to an energy deficit in nerve cells, harming their functioning; plus, the environment associated with MS lesions inhibits cell growth and also impairs remyelination.

Moreover, nerve fibers devoid of myelin also change their set of ion channels, accelerating the neurodegeneration process.

“In order to provide more efficient treatment, we will probably need precise therapy approaches targeting various pathomechanisms [disease mechanisms],” Faissner said.

Another problem is that the animal models currently available for researchers to study the disease and test potential treatments cannot mimic the full range of mechanisms underlying progressive MS.

That is why identifying potential therapeutic agents for a clinical study, for instance, “poses a considerable challenge,” said Faissner.

Another reason why it has been difficult to find treatments for progressive MS is the inconsistent efficacy criteria often used in clinical studies, the team said. Frequently, studies rely on different objectives, which means the way therapeutic success is understood and assessed varies from study to study.

Ideally, uniform criteria should be implemented to make studies comparable, and provide trustful results.

There also are financial aspects impeding the development of new therapies. According to Faissner, medications approved for other conditions could prove effective against progressive MS, but because patents for such products have expired, “pharmaceutical companies can’t further develop them.”

“The implementation of studies to test the efficacy of those drugs for MS often fails due to a lack of funds,” Faissner said.

Despite the challenges, researchers believe treatment for people with progressive MS will improve, as scientists gain a deeper understanding of the underlying disease mechanisms.

In Faissner’s opinion, these findings “will enable us to introduce a more targeted therapy that will prevent patients from suffering more severe impairments as the disease progresses.”

Ana is a molecular biologist with a passion for discovery and communication. As a science writer she looks for connecting the public, in particular patient and healthcare communities, with clear and quality information about the latest medical advances. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in genetics, molecular biology, and infectious diseases
Total Posts: 1,053
Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.
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Ana is a molecular biologist with a passion for discovery and communication. As a science writer she looks for connecting the public, in particular patient and healthcare communities, with clear and quality information about the latest medical advances. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in genetics, molecular biology, and infectious diseases
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6 comments

  1. SHARON MAIN says:

    I have PPMS, diagnosed March 2015 at the age of 66. No treatment approved until April 2017. By that time I was already in a wheelchair. I received the first Ocrevus infusion on May 1st 2017. After receiving 3 infusions it was determined it was not working on me as the disease had moved into my arms & hands.
    I had to purchase a sit to stand machine so my husband could get me up & down. I am still trying to keep some strength in my upper body but I seem to be losing the battle.

    • My husband has had PPMS MS four 50 years. There were no treatments for many years. He tried Ocrevus last year and came down with a bad UTI TWIand had to be hospitalized for 5days. Since then he has gotten worse quickly. He now takes menthenamine Hippurate 1mg tabs twice daily with 500 vit C which creates an environment in the bladder to prevent further UTIs. This is the only thing that actually helped him. I think it is imperative to keep fighting this damn disease by having continuous PT, OT, and speech therapy to keep everything moving. Exercise is very important. Try to keep laughing and keeping yourself in a good place mentally. You deserve it.

  2. Karen Wagner says:

    I have SPMS. I have been waiting 9 months to see an MS Dr. in NM. I was diagnosed last December by a neurologist. I am treating myself with lots of vitamins and Gabapentin. I am 64 years old. At age 16 I was diagnosed with GBS. We now think that was wrong and that I had my first MS attack. The disease has been mostly dormant for the last 48 years until now. Last August I woke up with a numb hand and foot on the right side and numb fingers and toes on the left side (the last two toes and the last two fingers on the left.) I will be glad to see a doctor to discuss this. I still don’t have an appointment until October. Wish me luck!!

  3. Jackie pearce says:

    Hi my name is jackie, I was Diagnosed in 2016 with ppms ,it was good to read about other people with ppms I still wonder if I have it .I’m not as bad as any of them patients. Is there such a thing as mild ppms . ?

    • Wjciech says:

      unfortunately, over time, all PPSM patients get worse. I am not surprised by the lack of entries from Poland, because in my country the treatment of this disease is limited to the fact that you could cope with it alone. Doctors are usually incompetent and my leg was amputated because of venous congestion because this was the reaction of my body to the administered drug and this is one of the effects of MS. I am 66 years old and I have been living with MS for about 20. Fortunately, those years were full of life and I did a bit of the profession I learned – a lawyer

  4. wadalbertb says:

    “Lack of progressive MS treatment has several causes, but …” And that’s terrible. Because, which means “lack of representative research models”. For me, this is the same as the lack of research models recognized in achieving a positive or negative result. The lack of applicable procedures and procedures, only that they arise during research in various environments, teams and bringing them to a common denominator is the process of selecting them from hundreds of already completed activities. It is like reaching into their history of any research in which exceptional results were obtained and on their basis developing methodological assumptions. Very difficult, burdened with omniscience and time consuming. But the team of experts doing this work should be, only who should call them?

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