Most of you who read the blog know that I’m highly cynical when it comes to the word ‘CURE’ in the same sentence as a brain disorder or autoimmunity. In fact, it’s very similar to hearing the word VEGAN in the same sentence as pizza or donuts (apologies to any vegans who are currently sitting across from one of these right now; there’s always tomorrow).
Where do I begin?….
Science is imperfect, with perfect people searching for imperfect outcomes (an oxymoron if ever there was one), we live on Earth (the only planet in our solar system not named after a mythical being, but deriving its name from Anglo-Saxon erda meaning ground or soil, so some realism is needed here), and we are but small ants in the bigger schemes of things etc., etc.
But, may be from time to time the Universe my yet throw us a bone, or more likely we simply stumble across the answer just by chance alone. Over this decade, in the space of just a few years, we have seen the greatest development in targeted gene therapies that science has to offer, and for the first time since their characterization, we have the hope of curing some of the world’s rarest and incurable genetic disorders.
So, why can’t MS have its moment in the limelight? In my opinion, HSCT (Hematopoietic Stem Cell Transplantation) currently offers the best opportunity of achieving this goal.
What should be the aims of HSCT treatment?
At worst, remission. At best, a cure.
Remission is when your clinical examination and MRI scans indicate that the MS is no longer active, i.e. “no evidence of disease activity” (NEDA). A cure, on the other hand, is when the immune system stops targeting your nervous system, i.e. there is no longer CNS-directed autoimmunity. How, you’d judge the latter is open to debate, but the authors in this publication (see below) feel that the disappearance of oligoclonal bands (antibody synthesis) in the cerebrospinal fluid (CSF) is a good indicator of this. They have also included into this definition stabilization of CSF neurofilament levels into this (i.e. no further ongoing neuronal injury).
This is a very, very small study (n=10), and the protocol is not the partial immunoblation that is now being used in the UK, but full clearance of the bone marrow using proper-chemotherapy (BEAM/ATG) mainly (although one person did have the low intensity cyclophosphamide/ATG conditioning regimen). Two out of the ten went onto have a clinical relapse, and were started on Copaxone (I note, with interest that the choice by the treating physicians was to go with a low-efficacy agent; possibly to reduce the future occurrence of PML (progressive multifocal leukoencephalopathy), which is more likely if a higher efficacy agent was used). But, overall 50% achieved remission, and 30% a cure (see Figure 1 below). I might add, that alemtuzumab achieved ~68% remission at the same time point, but we’re not comparing like with like here.
Of course, HSCT is not without adverse events, and some of the side effects described in the study would be considered serious in nature (see Figure 2 below).
But, if you are in that lucky 30% that achieve a cure with this treatment, then who am I to argue with the facts?
Acta Neurol Scand. 2019 Jul 12. doi: 10.1111/ane.13147. [Epub ahead of print]
Sustained remission in multiple sclerosis after hematopoietic stem cell transplantation.
Tolf A, Fagius J, Carlson K, Åkerfeldt T, Granberg T, Larsson EM, Burman J.
To determine if treatment with autologous hematopoietic stem cell transplantation can induce sustained complete remission in patients with multiple sclerosis (MS).
MATERIAL AND METHODS:
Case series of patients with relapsing-remitting MS (n=10) treated at a single center between 2004 and 2007 and followed up for 10 years. The patients were treated with a BEAM/ATG conditioning regimen (n=9) or a cyclophosphamide/ATG conditioning regimen (n=1) followed by infusion of unmanipulated autologous hematopoietic stem cells. The primary endpoint was sustained complete remission. Sustained complete remission was defined as ‘no evidence of disease activity-4’, sustained for a period of at least 5 years without any ongoing disease-modifying treatment. Furthermore, MS was considered as ‘resolved’ if intrathecal IgG production and cerebrospinal fluid neurofilament light levels were normalized as well.
Five out of 10 patients were in sustained complete remission at the end of the study. In 3 of them, MS was resolved.
Our data demonstrate that sustained complete remission after autologous hematopoietic stem cell transplantation for MS is possible.