Tuesday, 11 March 2014

Blood producing hormone promotes repair after relapse

EPO an exciting neuroprotective hormone that needs another look. #MSBlog #MSResearch

"This is a small proof-of-concept study looking at whether or not RRMSers do better from a relapse when erythropoeitin, or EPO, is given in combination with a steroid compared to a steroid in combination with a placebo. The study used both subjective and objective (MRI) outcomes. This study was positive despite the small numbers and hence will need to be confirmed. This study also builds on a body of literature that shows that EPO is neuroprotective. For example, we have reported on an optic neuritis trial showing similar results."

"EPO is an interesting hormone; it is produced by the kidney and has diverse effects on the body. Its main function is to stimulate the bone marrow to make red blood cells, but it also acts on other tissues of the body as a growth factor and the brain to protect neurons from dying. Interestingly, its effects seem to be mediated via two different types of receptors hence it may be possible to dissociate the blood forming effects from the neuroprotective effects by designing different types of EPO mimicking drugs. In fact, there are many companies trying to do just this at present. The one downside that needs to be avoided with EPO-mimics is neutralizing antibodies or NABs to EPO. If the EPO mimic induces the immune system to make antibodies to natural EPO, the NABs will cross-react with your own EPO and stop it from working. NABs to EPO cause a condition called pure red cell aplasia; essentially the NABs prevents EPO from telling your bone marrow to make red blood cells. In fact this is exactly what happened a decade or so ago when EPO came off patent and several biosimilar EPO formulations (generic equivalents) were launched. One particular biosimilar caused an epidemic of pure red cell aplasia. This event resulted in the regulatory agencies formulating very strict rules for generic biosimilars; manufacturers now have to show that they are safe and don't induce NABs. All this costs money hence biological, or protein-based, biosimilars don't bring down the price of the drugs very much; i.e. in the order of 30% compared to 90% with small molecule drugs. This is why there is a stampede by Big Pharma to get into biologicals; bigger profits, a longer shelf-life and less competition from biosimilars. You should not be surprised that most of the top selling drugs worldwide are now biological therapies."

"The other downside of EPO is its growth promoting effects on other tissues. This results in a greater cancer risk in those on EPO. This may be a problem for the EPO mimics as well. Therefore any drug development programme mimicing EPO biology is going to have to look into the cancer risk very carefully. This is unchartered territory and may be the killer of the class. The potential cancer risk with cladribine is what killed cladribine."

"I seem to rambling on. Overall this is a nice study and needs to be reproduced. I wonder who has the money and time to do it?"

"EPO was one of the compounds we looked at as part of our PROMISE 2010 programme. We were trying to develop a way of delivering EPO to the brain without exposing the rest of the body to its effects. Unfortunately, our test compound did not work in EAE in that EPO was delivered systemically. May be we should not have given up so quickly?"


Background: MS is a multifaceted disease in which genetic and environmental factors are involved. Although neurodegeneration aspect of MS has major influence in patients' disability, none of the available treatments have been shown to obviously reduce neurodegeneration. Recently, the role of Erythropoietin (EPO) as a neuroprotective and anti-inflammatory agent has been attracted tremendous interest. 

Aim & methods: In the present randomized double-blind pilot study, we combined EPO with methylprednisolone (MPred) in severe motor relapsing-remitting MSers to target both inflammatory and neurodegenerative aspects of disease. Twenty RR-MSers in relapse phase were randomized into two groups. The case group (10 MSers) received intravenous MPred (1,000 mg/24 h) and intravenous EPO (20,000 U/24 h) for five consecutive days, and the control group (10 MSers) received just MPred at the same dose as the case group, and a placebo. Both groups were followed for 3 months by ambulatory index (AI), Expanded Disability Status Scale (EDSS) and by magnetic resonance imaging (MRI) parameters.

Results: Improvement in maximal distance walking, reflected by reduction in AI and EDSS, was observed in EPO group after second month and continued after 3 months. Furthermore, MRI data analysis showed significant reduction in the number of T2WI lesions in EPO group without any significant change in contrast enhancing and black hole lesions. There was no major side effect in EPO group. 

Conclusions: The results of this first therapeutic pilot trial in RR-MSers are promising, but need to be validated in larger trials.

9 comments:

  1. What if it was injected into the brain, like baclofen?

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    1. It would reduce some of the side effects of EPO in the blood. However a pharmaceutical company has re-engineered EPO to produce carbamylated-EPO that does not have the blood doping capabilities but was neuroprotective in experiments. Is this being developed I don't know if not then maybe it has side effect issues.

      How does MS, do in high altitudes (maybe you need to adjust for higher vitamin D levels) as this is the natural way of stimulating blood cell production?

      High Altitude (oxygen) tent for MS, are our paralympian atheletes using these devices saving their brains?

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    2. Hyperbaric Oxygen JunkieTuesday, March 11, 2014 2:11:00 pm

      I suspect carbamylated-EPO will induce NAbs. High Altitude tents are designed to cause hypoxia, or low oxygen levels, the opposite what hyperbaric oxygen chambers do. The latter have been tried in MS and many people with MS are convinced they work, which is why the many centres in the UK providing this treatment continue to flourish.

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    3. Those who feel revived after a course of hyperbaric oxygen are certainly halucinating. There is not enough evidence to account for a beneficial role of oxygen to an oxygen-deprived CNS. The only way to see true benefit is to hit your MS hard and early with the latest collection of anti-inflammatory and neuroprotective drugs. Everybody please adhere to your medication and stop reading unvalidated internet stuff.

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    4. "High Altitude tents are designed to cause hypoxia, or low oxygen levels" yes exactly thereore it stimulates the prductin of EPO in order to stimulate red blood cell production to increase oxygen supply to tissues....This is why dubious atheletes blood dope, they inject EPO to make more red blood cells so that can consume more oxygen and with more oxygen you can feed more energy demands.

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    5. Is this a different VV??

      "The only way to see true benefit is to hit your MS hard and early with the latest collection of anti-inflammatory and neuroprotective drugs" is a change in stance

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    6. He obviously declined to use the sarcasm identifier.

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    7. "Everybody please adhere to your medication and stop reading unvalidated internet stuff".

      So within the last two weeks Dre and VV have had a change in stance on drugs and its not even April 1st yet

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    8. All available evidence suggests that optimal long-term outcome is achieved if MS is aggressively treated at the very first episode indicative of MS. No one should do what i have done. I may be 3 years free of disease activity in any possible, formal or informal way, but what i have done is dangerous and unsupported by recent objective literature. After all, at least 3 people died of it.
      Natalizumab is the way to go. It's a pity that it is only offered as a second line treatment, because it is very effective and has a clear risk profile. Only 9 people every month get PML and as few as 101 people have died amongst hundreds of thousands of total recipients worldwide.
      And even if get JC-positive you can always change to fingolimod and prevent the rebound effect.

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