Computer Says No

Anti-cancer therapy and Autoimmune disease:  Part II

Computer Says NoSo, 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.

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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

ResearchBlogging.org

AG McCluskey (2016). Computer Says No Zongo’s Cancer Diaries

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Collateral Damage

Anti-cancer therapy and Autoimmune disease:  Part I

Collateral DamageBit of a detour in this post, as I’m going to be talking about Autoimmune diseases.  There is a cancer connection though, which is the current trials into the use of anti-cancer therapy to treat these Autoimmune conditions.  But, in order to explain how this works, I need to explain what Autoimmune diseases are.  So, that will be the subject of this post.  In the next one I’ll go on to discuss the current attempts to treat these diseases with chemotherapy and radiotherapy.

So.  Here we go.  Autoimmune disease 101:

Autoimmune diseases are caused by errors in the patient’s immune system.  Now, your immune system is there to do a very specific, very important job.  It’s there to protect you against infection.  The cells of your immune system circulate through your body, looking for anything that doesn’t belong.  If they find anything, they attack & destroy it.  This is how you fight off viruses, bacteria, fungal infections, etc.

So that’s what the immune system does.  It wanders about, looking for a fight.  But why doesn’t it start a fight with your own cells?  Well, as I described back in No Cure For Cancer…? every cell in your body has a protein on the outside called MHC, which acts like an “identity card” for the immune system.  So, normally, the immune system will ignore any cell which has the correct “identity card”, which is why it’s so hard to activate an immune response to cancer cells.

But, unfortunately, in some people this system breaks down.  Their immune systems stop recognising the “identity card” on some of their cells, which leads to them being incorrectly labelled as foreign invaders.  It’s a bit like the reports we’ve all heard from Iraq & Afghanistan, where innocent civilians are incorrectly identified as Enemy Combatants and blown to bits.  “Collateral Damage” is the oddly benign euphemism for this.  And the same thing happens in an Autoimmune disease.  So, the immune system goes on the offensive and starts to attack the supposed “foreign invaders”.

Different cell types come under attack in different Autoimmune diseases. In Rheumatoid Arthritis it is the joints. In Scleroderma it is the connective tissue that surrounds your blood vessels & major organs. And in MS it is a specialised cell type called oligodendrocytes.  I’m now going to describe the situation in MS, but similar events occur in Rheumatoid Arthritis, Scleroderma and other Autoimmine conditions.

So, in MS, the cells that comes under attack are the oligodendrocytes, which are part of your Central Nervous System (CNS).  The CNS is how information moves from your brain to your body and vice versa.  So, if you feel hot or cold, hurt yourself or feel hungry etc, then the information travels up the CNS to the brain.  If you decide to move your arms & legs, pick your nose or whatever, then your brain sends the appropriate signals to your body via the CNS.  Now, the signals work like electrical currents travelling through your nerves, in much the same way as the electricity running through the wires that power appliances like your TV, tablet, PC, etc.  In these appliances, the electrical wires  are covered in plastic insulation to prevent short circuits, which can damage the appliance, possibly irreparably.

And, in exactly the same way, your nerves are also covered in insulation to prevent “short circuits” in your CNS.  This biological insulator is called Myelin, and it is made by the oligodendrocytes.  So, in people with MS, the out-of-control immune response attacks & destroys the oligodendrocytes.  This means that their bodies can no longer make the insulating Myelin which protects the nerves in their CNS.  Therefore, their nerves become exposed, and this results in “short circuits” in their CNS.  And this is what causes the symptoms of MS.

In other Autoimmune conditions, the same thing happens.  In Rheumatoid arthritis, the painful swelling and deformation in the patients’ joints is caused by damage to the cartilage and bone.  In Scleroderma, damage to the connective tissue under the skin and around internal organs and blood vessels, leads to hard, painful swelling on the skin, circulatory problems and organ failure.  But in each case, like MS, the real issue in the aberrant, out-of-control immune response.

Right!  Now you have a (very!) brief description of Autoimmune diseases in general and MS in particular.  In the next post, I’ll go on to describe the potential of anti-cancer therapies for treating these conditions.

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Bell, E., & Bird, L. (2005). Autoimmunity Nature, 435 (7042), 583-583 DOI: 10.1038/435583a

ResearchBlogging.org

AG McCluskey (2016). Collateral Damage Zongo’s Cancer Diaries

Best Laid Plans

Best Laid PlansWant to hear a joke?  A really, really good one?  Well I’ve got one for you, and it’s a cracker.  It’s one of those jokes that’s a bit dark.  A bit sick, if I’m honest.  And it’ll both tickle your funny bone, and leave you outraged.  Hopping mad, even.

Believe me.  When I heard it, the first thing I did was laugh out loud.  And then I got angry.  Really, REALLY bloody angry.  And the best of it is, that I am the butt of this particular joke.  Me, personally.  I’m the punchline.  Still want to hear it?  Well, here goes.  I just saw this headline in the Guardian:

Revealed: cancer scientists’ pensions invested in tobacco

Yup.  You read that right.  Like most other workplaces, researchers who work in UK universities – researchers like me – have a pension scheme.  Ours is called USS (University Superannuation Scheme) and it is used by the majority of universities in the UK.  So, every cancer researcher based in a UK university uses this scheme.

And, unknown to us, it seems that our scheme has been investing in the tobacco industry for years.  So, every university-based cancer researcher in the UK has, unwittingly, been indirectly profiting from cigarette sales.

Good joke, eh?  Isn’t that a doozy?

Now to say that I am unhappy about this particular state of affairs would be an understatement.  I’m not so much unhappy, as hopping bloody mad.  I’ve spent 20-odd years trying to develop new treatment options for cancer.  So, it’s more than a little galling to discover that I’ve actually, in all that time, been a total hypocrite.

When I retire and start to claim my pension, some of that money will be derived from the World’s most infamous cause of the very diseases I spent a career trying to treat.

I. Am. Not. Happy.

How could this have happened?  What were the directors of the pension scheme THINKING?  Well.  It’s pretty obvious, really.  They were thinking about one thing, and one thing only.  Profit.

We live in an age of Free Market Capitalism, where the only important consideration in any business, in any industry, is The Bottom Line.  Are you in the Red, or in the Black?  And how much are you in the Red or Black?  Profit is King.  It trumps all other considerations.  Morals?  Ethics?  Workers’ rights?  Pah!  As long as you’ve got a nice, fat number in the Plus column, then you’re laughing, right?  Job done.

And if you’ve gotten that number using methods that go against the fundamental principles of your stakeholders?  Who cares?  Screw ’em!  What are they going to do?  Give the money BACK?

So.  Was I surprised by the discovery that USS profits from tobacco?  Yes I was, naive fool that I am.  But was I shocked to the core of my being??  No.  It’s repugnant, but not shocking.  I know how the world works.

But that doesn’t make it RIGHT.  And it doesn’t mean that I just have to shrug and accept it.  This is wrong.  Plain wrong.  And I need to try and change it.  I don’t know how.  I don’t know if I can.  But I have to try, at least.

This is not over.

 

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ResearchBlogging.org

AG McCluskey (2016). Best Laid Plans Zongo’s Cancer Diaries