Mama Always Said, Life Was a Box of Chocolates. You Never Know What You’re Gonna Get – Forrest Gump, 1994 

A few years back Prof G, whilst talking about MS at a conference was approached by Takeda Pharmaceuticals on whether we would be interested in targeting plasma cells; probably one of the last frontiers in MS. The ideas started spinning from there. Roll forward a few years, after meeting the necessary regulatory and institutional requirements, there is finally light at the end of the tunnel. NDG, Prof G, and the whole SIZOMUS team now stand at the frontiers of new science in MS. It has been a team effort, and together with supportive colleagues and patients, the study is hitting its first safety review in May. The first five participants (anon.) who started SIZOMUS in September have been key to this. We are forever hopeful that many more will benefit from this work years to come.

So what SIZOMUS clinical Trial is about?

SIZOMUS is a short name for “Safety of IxaZOmib targeting plasma cells in Multiple Sclerosis”.

This is a clinical trial to investigate for the first time the role of “anti-plasma cell” therapy in multiple sclerosis. It is a Phase 1b clinical study, which means it is concerned with the safety of using anti-plasma cell treatments in multiple sclerosis patients. Ixazomib (trade name Ninlaro) is a 2nd generation proteasome inhibitor. It triggers the apoptosis (programmed cell death) of cancer cells including malignant plasma cells (called multiple myeloma). 

Why we should target Plasma cells in MS?

One of the main characters in the MS story is the presence of “antibodies”. These antibodies are key players in immune attack against different foreign agents such as bacteria and viruses and it is well known that plasma cells are the main factory for producing such antibodies.

In MS some of these plasma cells have been shown to relocate their domain to the brain and spinal cord, where they persist in their antibody production causing slow burn inflammation. However, most of the available artillery for MS do nothing to plasma cells; of course a plasma cell “can be” affected when you target its predecessor, the B cell but otherwise they are pretty much resilient. Plasma cells can survive for long-time once developed and continue to exert ongoing damage unless you specifically target them.

SIZOMUS study is the first of its kind to pave the way in answering the question of whether targeting these plasma cells will improve outcomes and hopefully reach the unmet need of stopping disease progression at the end.

Ready steady go! How can I participate?

If you are living in the UK with a diagnosis of MS and you are between 18-65 years of age, this is sufficient to contact the study and check for your eligibility further.

We will make sure that you are:

  • Stable on your MS treatment (DMT, disease modifying treatment) if you have the relapsing-remitting form of MS (RRMS)
  • Not on any DMT if you have the progressive form of MS (PMS)
  • Have a CSF sample from a lumbar puncture (LP) which shows the presence of OCB, if you never done it before, we will repeat the LP at the screening visit of the study
  • Agree to use contraception
  • Be willing and able to provide written informed consent to participate
  • Agree to comply with the requirements of the study protocol
  • Be reasonably fit and able to attend study visits.

Also, we will make sure that you do not have any of the following:

  • Have had a MS relapse within the last month
  • Be pregnant or breastfeeding
  • Have had recent major surgery
  • Have a serious infection at the time of the screening visit, or a history of HIV, hepatitis, tuberculosis or syphilis infections
  • Have any other serious medical or psychiatric condition, which in the doctor’s opinion may make it inappropriate for you to take part. This includes certain cancers, uncontrolled heart conditions and any other neurological disease apart from MS.

What does Taking part involve?

The study consists of anumber of steps taking place at the Royal London Hospital.

  • Screening and baseline phase (lasting up to 8 weeks)

During this phase we will make sure that you meet all the eligibility requirements mentioned above through clinical assessment as well as many tests and procedures.

  • Treatment phase (from the first dose to the last dose of study drug, lasting 24 months)

Once everything is ready, you will either receive the treatment pills or dummy pills (you will not be able to tell which is which, they would both look the same).

The study drug is taken once a week for the first three weeks of every month.

The initial three visits will be in person 2 weeks apart to ensure participant safety, followed by monthly visits thereafter (24 months). If things are fine some of these visits will be converted to telephone calls.

During each study visit, we will go through clinical assessment, compliance on the treatment and check for any side effects, as well as laboratory tests for safety and measures of efficacy. There is an MRI scan at baseline (time 0), year 1 and year 2. There is also an LP at these three visits for the oligoclonal band test (antibodies) to see if individuals on Ixazomib loose their antibodies over time.

If you are happy to have further discussion about your participation in SIZOMUS: Please feel free to contact me

Dr Mohammad Aboulwafa (Dr Wafa)
Clinical Research Fellow for the SIZOMUS trial
11D department of Royal London Hospital: 02035540637 / 02035540638

SIZOMUS team left to right on the 15th floor of The Royal London Hospital: Dr Mohammad Aboulwafa (Wafa) – Clinical Research Fellow and main study contact, Dr Sharmilee Gnanapavan (NDG) – Chief Investigator, Dr Michael Andrews – Clinical Research Fellow, Francesca Ammoscato – Post Doctoral Research Fellow in Head of Labs, Dr Lucia Bianchi – Post Doctoral Research Fellow and Research Manager. Prof G is present in spirit!

Disclaimer: Please note that the opinions expressed here are those of the author Dr Wafa and NDG and do not reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust or Queen Mary University of London.

About the author

Dr Wafa


    • This is the licensed dose of Ixazomib in multiple myeloma. Dosing curves have already been performed to make this the optimal one.

  • I would love to participate in your study but unfortunately I don’t live in the UK. 🙁 However, I just wanted to wish you best of luck with the study! ❤

    • If you have RRMS on DMT and not noted to have low lymphocyte counts, you don’t need to stop your existing DMT. PPMS and SPMS individuals shouldn’t be on a DMT to enter the study (this is because we do not know what the interaction between an additional agent on top of an existing DMT would be in those with more disability and comorbidities).

  • Appreciate your effort but could you clarify on “probably one of the last frontiers in MS”. What are the frontiers that are to be explored?

    • The innate immune system is something that researchers are only now focussing on – microglia, neutrophils, mast cells. Every person with MS is different with different drivers to their disease. We’ll need to tailor treatments accordingly in the future.

  • “hopefully reach the unmet need of stopping disease progression at the end.”

    Excellent work. Thank you for all your efforts. Stopping progression is the holy grail of MS research – it’s the insidious neuro-degeneration which makes MS such a horrible disease.

    How do plasma cells relate to memory B cells?
    Has the approach of targeting plasma cells been used in other “auto-immune” diseases? (with any success?)
    Does Prof G know that you are using his lovely office while he recuperates at home?

    • NMOSD with quite good results as it is antibody driven disease. Small pilot study with interesting results.
      Lupus with lupus nephritis with decrease of proteinuria and improvement of disease index. Search KZR-616. Same drug used for poly and dermatomyositis.

        • I liked the study from the first time I have read of it, so I am glad to help… unfortunately, I do not live in the UK otherwise I would help also asking to be enrolled 🙂

    • Hi Sid
      Plasma cells, which secrete antibodies) are the last stage in the B cell lineage and are derived from plasmablasts which are themselves derived from memory B cells. Plasma cells haven’t been specifically targeted per se but anti-CD 19 has been used in other autoimmune conditions with success and se veral trials are ongoing with anti-Cd20 BTK inhibitors and also now prteosome inhibitors. The outlook looks promising.

    • Thank you..

      Memory B cells and plasma cells are both end lines for Activated B cells, and in a way both are long-lived cells that never forget!

      Anti plasma cell therapy has shown some promising success in systemic lupus erythematosus and we are excited to know if this will be the case for MS. This is a smart question really, thank you for it.

      Prof G is fully occupying his room now (and our hearts :D) , he is continuing his full work thankfully.

  • Hi Dr Wafa
    I have enjoyed your recent posts. Good luck with the trial. Nice to see the faces behind the blog too

  • So uplifting to read about this study🙂
    Don’t feel up to study participation, but hope you’ve the necessary volunteers asap.
    Very best wishes with this – with hopefully the benefit of Covid vaccine knock on = study taking far less time than you all initially envisaged!

  • DR WAFA, is there evidence of OCB negative pwMS do better than those with positive OCBs in the long term? And if ocrelizumab/rituximab/ofatumumab help to clear OCB bands in CNS after a while?

    • Very nice questions..thanks for that..

      There is an evidence that OCB negative pwMS have better progosis indeed. However -in my opinion- this should not be taken as a universal rule. We know that OCB differes in prevalence according to latitude and in some places of the world OCB is less prevalent and MS is more aggressive.

      Anti CD20 therapy does not show an effect on OCB positivity so far, which should be expected given that these treatments does not cross to the brain and the spinal cord where the cells that produce OCBs live.

      • Thank you for the reply – I was hoping without mediated by the B cells, plasma cell will disappear after a while, but as there are ones live a life long so I understand.

  • I meet all the criteria but one and have a long and respectable history of Being Part of Research; always participating fully through to the conclusions of the study, except where it’s longitudinal and open ended. I fail on one criterion; age. Some of the participants may be 65 at the commencement of the study, therefore >65 at its conclusion, so why not include older patients. After all, MS doesn’t go away.

    • Thank you KIT for your interest and your very positive attitude for participation in clinical trials.

      This is the first time to trial anti-plasma cell theray in MS and so we are a ‘safety concerned’ study. So the study design tries to minimize the risk and one of them is age.

      I hope this study comes up with positive safety data and we be able to welcome you in the future 🙂

  • If the trial gives positive results what should we expect to happen next? An expansion to ph2 size or a separate trial?

  • Thanks for the kind words Dr Wafa. Include me if you can at some point in the future if the safety data are promising. I bet older pwMS would be likely to throw out some interesting comparative data.

By Dr Wafa



Recent Posts

Recent Comments