Promoting Remyelination in Multiple Sclerosis – an Interview on rHIgM22




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The Mayo Clinic and Acorda recently enrolled the first patient in their phase 1 clinical trial of a remyelinating antibody that may potentially reverse the damage caused by multiple sclerosis. I recently interviewed Anthony O. Caggiano, MD, PhD, Vice President of Research & Development at Acorda since February 2009. Since joining Acorda in 2001, he has served in various roles in preclinical science and research and development, directing basic research and product development efforts, coordinating external research programs with academic and commercial partners, and collaborating in business development activities.

SL: What is the current state of knowledge on the pathogenesis of multiple sclerosis?

AC: In multiple sclerosis (MS), a person’s own immune system destroys myelin, a substance that insulates nerves and facilitates conduction of nerve impulses that control neurological function such as movement and vision. Without myelin, the neurons in the brain, spinal cord or central nervous system communicate less effectively.

Progressive damage to myelin causes functional impairment in people with MS. Currently there are no approved therapies that stimulate the repair or regrowth of myelin once it has been damaged. Acorda is now studying an antibody called rHIgM22 which has been shown to potentially stimulate remyelination and improve the function of neurons.

SL: How do our current lines of treatment for MS affect the disease course?

AC: There are two main categories of MS treatments. The first involves the use of disease-modifying agents (interferon beta-1a, interferon beta-1b, glatiramer acetate, natalizumab and fingolimod), which have been found to help with relapse management, decrease MRI activity and potentially delay disability. The second category is treatments that target specific symptoms of MS, such as AMPYRA (dalfampridine), which is indicated to improve walking in people with MS.

Disease-modifying agents are an important part of managing MS, and evidence suggests that they can be combined with other treatments to target different aspects of immune response or therapeutic targets such as inflammation or neuroprotection.

SL: How was rHIgM22 identified and what does it target?

AC: rHIgM22 was identified by a team at the Mayo Clinic led by Moses Rodriguez, MD, a neurologist specializing in MS. It is a monoclonal antibody that interested Dr. Rodriguez because of its ability to enhance the repair of the central nervous system (CNS). The cells that make myelin, called oligodendrocytes, can initially repair myelin, but as MS progresses, there is little spontaneous repair. Dr. Rodriguez’s team identified antibodies in mice that promote remyelination and then identified similar antibodies in humans. rHIgM22 is the lead of these human derived antibodies and has been shown to bind CNS myelin, stimulate oligodendrocytes and promote remyelination in animal models.

rHIgM22 is currently being studied in a double-blind, randomized, single ascending dose Phase 1 clinical trial in people with MS. This study will measure the safety and tolerability of rHIgM22 as well as any changes in the MRI results of treated patients. Evaluations of changes in MS symptoms, such as walking ability, will also be conducted.

SL: What is in on the brinks of translating from the benchside to the bedside in MS?

AC: Many researchers are continuing to develop disease modifying therapies and symptom management medications in MS, but research related to remyelination is positioned as a major focus in research in the years ahead. Such therapies have the potential to represent a novel and significant advance in MS care.

References

Rodriguez M, Warrington AE, & Pease LR (2009). Invited article: human natural autoantibodies in the treatment of neurologic disease. Neurology, 72 (14), 1269-76 PMID: 19349608

Watzlawik J, Holicky E, Edberg DD, Marks DL, Warrington AE, Wright BR, Pagano RE, & Rodriguez M (2010). Human remyelination promoting antibody inhibits apoptotic signaling and differentiation through Lyn kinase in primary rat oligodendrocytes. Glia, 58 (15), 1782-93 PMID: 20645409

Watzlawik JO, Warrington AE, & Rodriguez M (2013). PDGF is required for remyelination-promoting IgM stimulation of oligodendrocyte progenitor cell proliferation. PloS one, 8 (2) PMID: 23383310

Image via martan / Shutterstock.

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  • misty werth

    Take me. You saved my life in 2006. Use me as a study. Please

  • http://www.mammananny.com Linda Rousay

    How can you possibly expect to reverse the damage done to the nerve endings when you don’t even know what causes it? For 6 decades neurologists and MS Societies having hinted at an autoimmune theory which has not yet been proven even to the satisfaction of you or your colleagues. There is no credible or unbiased proof or studies that show that the disease modifying drugs do anything to shorten relapses.

    • Kim

      Linda,
      This is not a DMD. This is a monoclonal antibody that Dr. Rodriguez has discovered. He is my neurologist and I know he has been able to re-myelinate mice and monkeys. He was also able to restore function in these animals. He has been waiting years to start human trials! I think we should be excited and hopeful that there are doctors who spend their whole life trying to help people like us, who have MS. I think you should educate yourself before doubting. You never know what might happen. I choose to remain hopeful, even though I have SPMS. Please read:

      Another update on the re-myelination human trial!! I’m very excited to say the least! Dr.Rodriguez is my neurologist! He has re-myelinated mice and monkeys and just now finally started human trials of the momoclonal antibody he dicovered, after waiting many years!! If you have MS or know someone who does, please pass this info on! Linda, I hope we all get help! http://mayoresearch.mayo.edu/mayo/research/rodriguez_lab/remyelination_update.cfm

    • Angela Spindler

      Linda, I almost didn’t give Liberation a try either. Four treatments later I’m out of $ and my stented RJV is clotted off requiring vein replacement only done out of the states. My 1st two procedures (5/10, 12/10) gave me great results. Not so much for the two in ’11. I’ve been a fan and follower of yours since the start as I still am today but as all of our results weren’t as lasting as yours I have to praise God that somebody somewhere is looking for repair.

      Maybe if this antibody can repair faster than the MS can destroy I may not need a new vein. Maybe all those being LIBERATED will only have to do it once. Start this antibody and commence with steady continued healing, can you imagine? I pray this works! The article’s intro about current treatments shouldn’t deter a pioneer such as yourself! Hoping you’re still out there trailblazing! Love ya, Angela

    • SPIRO SPYRATOS

      As mentioned elsewhere on this thread, it is not a DMD but a remyelinating agent. Almost all research points to MS being an autoimmune response against myelin and its proteins. How else do you explain the effectiveness of immune suppressants or immunomodulating treatments? Hoping that it’s caused by something else is wishful thinking on patients’ part, for example, CCSVI, proven time and again to be no better than placebo and can even be dangerous.

  • Beth Thomas

    This sounds promising and for the naysayers, it will not hurt to try and see if this helps. If it doesn’t, then at least he can say he tried.

  • Arthur Leeper

    I am old enough to clearly recall the period when scholars firmly believed that every part of the body had a repair mechanism… except for the brain. And some thirty years ago the research that was based on was reexamined and found to be false.

    What has been learned is that nerves and brain cells can regenerate and repair themselves, the problem with MS being that the rate that damage is being done exceeds the body’s ability to keep up, even though the repair mechanisms work to their maximum efficiency. Sorting out which of the chemical mechanisms in the body can aid in the repair of damaged myelin sounds both entirely possible and to be a really good idea. The damage that MS causes to individual lives and the cost of healthcare in this country is considerable. And growing. It has been noticed that at the present time three times as many women get MS than men, a broader ratio than ten or twenty years ago. Why? Figuring out why is obviously an important direction for research, but in the meantime there are 400,000 Americans who stand to benefit from work like this.

    • Joan Quilter

      400,000 was the number 20 years ago, and yet it is still being used.

  • Pearl Smith

    Why does it take so long to perform clinical trials? I remember reading about rHIgM22 at least 3 years ago. I was diagnosed with Secondary Progressive MS 10 years ago. I’ve been in a wheelchair and was forced to retire two years ago. By the time they fix MS, I’ll be long dead.

    • http://lori.wilson.friend@gmail.com Lori Friend

      There are procedures that have to be followed to make sure not just that it will work along with safety issues for human consumption. FDA okay’s have be had for many steps along the way as well and we all know how quickly the government works. Add ALL that with the length of the actual trial, time matters. If they didn’t and something happened, then people would complain about that.

    • Kim P.

      Dr.Rodriguez is my neurologist.He said that it takes so long because he had to write a 10,000 page paper about his research to be submitted to the FDA! Also, it takes a lot of money! I know I have heard about this monoclonal antibody for 3 years, but I think he has been working on this for over 10 years! I know it is a lot more complicated than we know! I have read some of what he has written about his research. It is very deep and complicated! All I know is that I am thankful it is finally in the trial phase.I too have SPMS and have lost function. But, I appreciate what Dr. Rodriguez is doing! I am hopeful, even though it will still be awhile before it would be approved.

  • Regina Beaulac

    I’m secondary progressive and I would be very willing to enter a clinical study for this therapy.

    • Kim P.

      Contact the FDA.Dr.Rodriguez said that he doesn’t get to choose who gets in the trial.

  • Angela Spindler

    I’m SPMS too and would love in on this!!!

  • http://Yahoo Chuck Huckaba

    I have been diagnosed with Primary Progressive MS and I feel that anything that may help would be a Godsend.

  • Theresa Stoddard

    I was officially diagnosed with RRMS in 1996, I am still RRMS ….ms sucks. I want to try the remyelination medicine, I want to participate in trial very, very much.

  • Nishaad Anantani

    Hello, This is very encouraging news indeed. I am from India and my wife has been diagnosed with RRMS 6 months ago.

    We would be willing to participate in trials if any going in India.

    Rdgs
    Nishaad

  • Randy

    I am an RN and my wife is wheelchair bound with PPMS.

    The information for the clinical trial can be found at:

    http://www.clinicaltrials.gov/ct2/show/NCT01803867?term=rHIgM22&rank=1

    Realize that the primary endpoint of this study is to evaluate the safety and tolerability of the investigational product in patients with MS. Secondary to that is the dose levels, PK as well as neuro assessment based on the EDSS. There is no preference over what stage of MS someone is in, as it is open to all stages and they want a variety.

    For my wife and I, this trial gives us more hope than in the past. It has been shown to reverses the breakdown of the myelin sheath in the lab animal trial (4000 x the recommended dose was given without adverse effects). This is just the start of the human trial. My wife is applying for the trial in Denver. It’s going to be a long shot for all of those applying. Good luck and let’s hope it’s successful !!

  • Randy

    I forgot to say: From what I’ve read, there will be only be ~ 80 to a hundred candidates nationwide . . . And several of those individuals will get the dreaded placebo. It’s going to be a long shot to be selected :-)

    • John

      How does one apply for the trials?

      • Randy

        Go to the site I listed. It gives you the locations of the trial sites and the contact information. BTW: Big pharmacy (Acorda) is funding the trial.

        • Angela Spindler

          Thank you so very much for sharing the info w/us Randy. May God continue to bless you and your wife. We have to start somewhere, right? Placebo or not, I say lets get this started.

        • Chris

          Acorda is not considered Big Pharma (like Novartis). Acorda is more like a promising start up company. I hope Acorda keeps up its good and ground breaking research. It is great that it develops drugs for all levels of MS and not just RRMS. Best of luck to Acorda!

          • Randy

            I stand corrected. Let’s hope and pray that if successful, rHIgM22 and Acorda doesn’t get bought out and/or research stifeled by Big Pharma . . .

            Being a nurse, I understand why most research is geared toward RRMS. I was surprised to get this email from Dr. Moses Rodriguez back in early March:

            “The phase I clinical trial will include all forms of MS- I do not know when the trials will start but I suspect by summer. All sites will be outside of Mayo Clinic: since Mayo is the inventor we have a conflict of interest and therefore we cannot enter patients at Mayo. Mayo patients can be involved in the trials but will have to be evaluated at a different sites. The sites will be decided soon. Moses”

            ALL FORMS OF MS !!!!

            There is Hope . . .

          • Angela Spindler

            Great info about Acorda, Chris. Looked stuff up today and prayer answered they’re testing 3 1/2 hrs. and 5 hrs. away from me. Praying harder now. Even crossing fingers. ;-)

          • Chris

            That sounds great Angela. Best of luck to both of us and everybody listed here.

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  • Dawn

    Finally! A study focused on repairing the damage caused by this disease, as opposed to another “disease modifying drug” designed to prolong or “delay” the damage. This could also prove to help those with other demyelinating diseases, remember Lorenzo Odone, the little boy in the movie,”Lorenzo’s Oil”? I have SPMS. I will be the first to volunteer if the opportunity arises! Imagine the possibilities??

    • Angela Spindler

      Amen!

  • John

    It all sounds so good but why is the myelin sheath being destroyed in the 1st place? And I highly doubt that big pharma will be enthused to have this re mylenating process come to fruition sadly.

    • Randy

      You are correct . . . This trial does not address the cause of the myelin breakdown. A few big questions that I still have and I have not found in my rHIgM22 research readings. Once given, do the antibodies reproduce/stay in circulation and continue to induce re-myelination – Sort of like a bone marrow transplant? Does one require multiple infusions to keep up de-myelination?

      • Angela Spindler

        Sad yes, John and great questions, Randy, BUT if they can fix faster than destroy let’s celebrate this find and get to the bottom of it later … just sayin’ … time is of the essence for some of us.

    • Chris

      John is right about big pharma. Big pharma is more like HUGE pharma and they spend more now than ever before to shut down new approaches and companies than to do any new development. They spend most of their money on commercials and research gets stuck in the mud. I worked in Big pharma research for 35 years and this unfortunately is what is happening now. So Accorda is stirring things up and I feel there is some hope. I have SPMS and I am also hoping to get on the rHIgM22 drug trial.

    • amber

      your own immune system is destroying the myelin for some reason you body is thinking your myelin is a virus or something like all people with autoimmune disorders like MS have very high white blood cells…think of your brain and spine as an electrical cord the white blood cells eat the out side of the cord leaving bare wires. this drug is made to lower your immune system giving your body a chance of repairing itself……

  • Angela Spindler

    Sent a couple e-mails, made a few calls, and because of the time difference was woke EARLY last week w/a return call to get more info from me. Two days later a packet of info arrives. PRAISE GOD! 1st order of business is to celebrate the 4th w/my boys, then nothing but paperwork this weekend. Moral of the story: Make a call! May God bless each of you commenting and reading w/all you need to fight this MonSter! <3

  • http://www.biobrea.com/ aaliyah

    Very Nice website. I just finished mine and i was looking for some ideas and your website gave me some.Primary antibody

Shaheen E Lakhan, MD, PhD, MEd, MS

Shaheen E Lakhan, MD, PhD, MEd, MS, is executive director of the Global Neuroscience Initiative Foundation (GNIF). He is a published scholar in protein biomarkers, bioethics, biotechnology, education technology, and neurology. He serves on the editorial board of several scholarly publications and has been honored by the U.S. President and Congress.
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