Anti-cancer therapy and Autoimmune disease: Part II
So, in my last post I gave a brief description of Autimmune conditions. Now, I’m going to describe the ways that research into cancer treatments is impacting on these diseases.
There was a big splash in the Media last Friday about a potential new treatment for certain forms of Multiple Sclerosis (MS). And the basis of that treatment? Chemotherapy. Yes, that’s right, cancer chemotherapy. MS patients are being treated with high doses of chemotherapy drugs to try and alleviate their symptoms. But why would you do this?? And how can it work?
I’ve spoken before about the common side-effects of cancer therapies such as chemotherapy and radiotherapy. Back in Bullseye! I described how these treatments can damage the patients’ immune systems. And this can be very bad for the patient, obviously. But the thing is, something which is bad in one setting can actually be good in another.
Listen to me! I sound like one of those self-help books. Turn that frown upside down! Accentuate the positive, eliminate the negative! Take a sad soooong and make it better….. But this, in essence, is the basis of the new treatment for MS that is being investigated.
So MS, like other Autoimmune diseases, is caused by an out-of-control immune reaction. So, what could you do to you fix it? How could you get the immune response back under control? Well, conventional treatments have tried to suppress the immune response in these patients. This has only had limited success, unfortunately. This led some researchers to consider something more drastic. They decided to treat the immune system like a computer.
Picture the scene: You’re on your PC, and it stops working. What do you do? Easy. Chances are, you switch it off, then switch it back on again. And you hope that this’ll fix the problem. But what if it doesn’t work? What if you find that the program is corrupted? Well, you can erase the corrupted version from your hard-disk and then re-install a clean version. And this, essentially, is the concept behind the new treatment for MS.
In cancer patients, there is an extreme form of treatment that is sometimes used which involves very high doses of chemotherapy or radiotherapy. Now, this may, or may not, destroy the patient’s tumour. Obviously, it’s hoped that it’ll be the former! But one thing it definitely will do, as a side-effect, is destroy the patient’s immune system. This is obviously not great, so in order to mitigate these unwanted side-effects, clinicians will repair the damage to the patient’s immune response by restoring the immune system after treatment. They do this using a technique called haemopoietic stem cell transplantation.
The haemopoietic stem cells live in your bone marrow and are the cells which give rise to all the different types of immune system cells. These are destroyed by the high dose therapy and this is what damages the patient’s immune system irreparably. So, knowing this is going to happen, clinicians remove some of the haemopoietic stem cells from the patient and store them before the high dose treatment is administered. After the treatment has finished, the clinicians can then put the patient’s haemopoietic stem cells back into their body, where they will grow and divide, and recreate the patient’s immune system.
So, that is what happens in cancer. But how does this apply to MS? Well, clinicians realised that what was a negative in a cancer setting – the destruction of & replacement of the immune system – could be a positive in the case of Autoimmune diseases. Autoimmune conditions are caused by aberrant immune responses, and high-dose chemotherapy or radiotherapy destroys the immune response.
So clinicians theorised that, like a computer, the use of high dose anti-cancer therapies, coupled with haemopoietic stem cell recovery & transplantation might erase the corrupted version of the patients’ immune systems and replace them with a rebooted, correctly functioning version.
So, a trial was conducted where haemopoietic stem cells were isolated from 24 MS patients. The 24 patients were then dosed with very high doses of chemotherapy drugs, which destroyed their immune systems. Then, the haemopoietic stem cells were put back.
Now. Sounds easy, yeah? Well…..no. This treatment is not straightforward. Far from it. It is incredibly tricky. And, it is incredibly risky. Chemotherapy drugs can have very, VERY nasty side-effects – and not just against the immune system. Indeed, one of the patients actually died during the course of this treatment, and all of the others suffered from a variety of pretty serious side-effects. So, not a walk in the park, by any means.
But, in the 23 patients who survived the treatment, the early results seem to be very promising. Their rebooted immune systems appear, so far, to be functioning normally, with no evidence of MS-related activity. Some of them have reported that their symptoms have stabilised. Others have actually seen an improvement in their conditions, recovering their mobility and quality of life.
So, all good, so far. And, as well as MS, similar studies are ongoing in patients with other Autoimmune conditions, such as Scleroderma. Now it’s still early days. There’s no way of knowing how long the rebooted immune systems in these patients will maintain their normal function. Hopefully, their immune systems will remain normal for a very, very long time. But, it’s possible that their rebooted immunity might contain the same flaws as the original, so that the Autoimmune conditions re-emerge. But even if this is the case, when could this happen? Dunno. There’s no way to tell yet.
Also, there is no way of knowing what other long-term effects will be caused by the high dose treatments. This approach is basically using a sledge-hammer to crack a nut – it hits the immune system, certainly, but it hits a lot of other things too. Studies of cancer survivors have shown that these high dose treatments can damage the digestive system, liver, kidneys, cardiovascular system and many others. And a lot of this damage may not become apparent for many years after the treatment has ended. So, it’s likely that similar side-effects will also be observed in the follow-up studies of the MS & Scleroderma patients taking part in these trials. So, a lot (and I mean, a LOT) of extra study will be needed to work out the long-term health risks of this approach.
But remember, this is just the early stages of this type of approach. If it can be shown to have real long-term benefits, then it will help drive research into finding more immune-specific treatments that can avoid potential off target side-effects. That still needs to be determined though. All we can say is that for now, for right now, we have a therapy which has the potential to be a major breakthrough in the treatment of MS, Scleroderma and other Autoimmune diseases.
Dr Harold L Atkins, MDcorrespondenceemail, Marjorie Bowman, MScN, David Allan, MD, Grizel Anstee, MD, Prof Douglas L Arnold, MD, Prof Amit Bar-Or, MD, Isabelle Bence-Bruckler, MD, Paul Birch, MLT, Prof Christopher Bredeson, MD, Jacqueline Chen, PhD, Prof (2016). Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial The Lancet : http://dx.doi.org/10.1016/S0140-6736(16)30169-6
Craciunescu, O., Steffey, B., Kelsey, C., Larrier, N., Paarz-Largay, C., Prosnitz, R., Chao, N., Chute, J., Gasparetto, C., Horwitz, M., Long, G., Rizzieri, D., & Sullivan, K. (2011). Renal Shielding and Dosimetry for Patients With Severe Systemic Sclerosis Receiving Immunoablation With Total Body Irradiation in the Scleroderma: Cyclophosphamide or Transplantation Trial International Journal of Radiation Oncology*Biology*Physics, 79 (4), 1248-1255 DOI: 10.1016/j.ijrobp.2010.05.036
AG McCluskey (2016). Computer Says No Zongo’s Cancer Diaries