Thursday, 12 February 2015

ClinicSpeak: lemon verbena biomarker study

Why the nutriceutical have an uphill battle to see the light of day. #MSBlog #MSResearch #ClinicSpeak

"The biomarker study below shows that lemon verbena a dietary supplement reduces pro-inflammatory cytokines and markers in MSers compared to baseline. The author's imply that lemon verbena has anti-inflammatory effects that may help MS. This is really a proof-of-concept study and should lead to a full development programme to find the component in lemon verbena that is responsible for these effects. The active ingredient(s) could then be extracted or synthesised and tested in EAE or similar animal model of MS. Depending on how effective it is the investigators' may be able to define some novel IP (intellectual property) and patent the substance as a treatment for MS. The patent is essential if the investigators want to attract follow-on funding. The ideal route for the latter is outside of academia as a University spin-off company. The start-up money can then be used to do the necessary work on developing a formulation of the compound(s), establishing the pharmacokinetics and pharmacodynamics of the new drug, doing toxicology studies in two animal species (e.g. rats and dogs). By this stage the initial round of funding will be spent, 6-8 years of patent life will be gone and big Pharma will want phase 1 (first in man) and phase 2a (proof-of-concept) data before investing in the compound. The academics who have started this University spin-off will now have to attract a second round of funding, only this time it will need to be much larger. Phase 1 toxicology studies will need to be contracted out to a CRO (contract research organisation) at great expense. The phase 2a study will need to be designed; will it be a simple baseline-line vs. treatment period (similar to what we have done with INSPIRE) or parallel-arm placebo controlled frequent MRI study? Industry and serious investors will almost certainly want the latter. After the phase 1 & 2a  studies another 3-4 years of patent life have expired and Big Pharma will be asking if there is really enough time left on the patent to do the necessary dose-finding 2b study and a full phase 3 programme to justify their investment. They business people will being say the anti-inflammatory market in MS is saturated and with small molecules off-patent, or due to come off patent, the market will be much less competitive. I predict that Pharma will say no thanks and the academics will be depressed that they have dedicated 15 years of their research careers to a project that has not be commercialised. Why am I so negative? It is simple, almost all new activity in the MS anti-inflammatory field is with repurposed or me-too drugs; i.e. a low-risk strategy. Very few companies are trying new anti-inflammatory drugs. This is why lemon verbena, or its active ingredient, has almost no chance of getting developed into an anti-inflammatory drug for MS using the standard pharma development approach."


"I hope I have made the point that the current Big Pharma model is almost certainly missing many effective drugs. This is another reason why we need an alternative model." 

"The other option for MSers is to simply take lemon verbena without any real data to support it efficacy in MS. This is the usual route of nutriceuticals. Please note that nutriceuticals are not without problems. They may for example contain toxic substances or metabolites that in small doses are not a problem, but as soon as you start using them in pharmacological doses side effects appear. Nutriceuticals can also interact with other medications and cause problems. This is why we can't recommend them to our patients; evidence-based medicine is brutally blunt."

Mauriz et al. EFFECTS OF DIETARY SUPPLEMENTATION WITH LEMON VERBENA EXTRACTS ON SERUM INFLAMMATORY MARKERS OF MULTIPLE SCLEROSIS PATIENTS. Nutr Hosp. 2014;31(n02):764-77

Introduction: Inflammation is one of the main contributory factors to the etiopathogenesis of MS. Dietary interventions with Lipia citriadora (lemon verbena) extracts have been proved to be effective in the prevention of inflammatory diseases. 


Objectives: The aim of this study is to evaluate the effect of lemon verbena supplementation in pro- and anti- inflammatory serum biomarkers of MSers with different clinical sub-types of MS.

Methods: The effect of lemon verbena supplementation (10% w/w verbascoside) was evaluated in a randomized, double-blinded placebo-controlled study with 30 participants classified in relapsing-remitting (n=10), primary progressive (n=5) and secondary progressive (n=15) MS presentations. Serum cytokine and C reactive protein levels were assessed in intervention and control groups for each MS clinical subtype after 28 days of dietary supplementation.

Results: Serum levels of C reactive protein and 8 cytokines/ inflammatory (IFN-G, IL-12, IL-23, IL-6, TNF, TGF, IL-4 and IL-10) markers were studied. Secondary progressive MS-supplemented MSers showed C reactive protein concentrations significantly lower compared to the placebo group (p<0.005). IFN-γ levels decreased for all MS-treated groups whereas IL-12 diminished levels were observed for relapsing-remitting type (p<0.05). Anti-inflammatory cytokine concentrations of  IL-4 (difference 2.98 ± 2.99 pg/mL) and IL-10 (difference 1.78 ± 5.54 pg/mL) increased in secondary progressive MSers (p<0.05). 

Conclusion: The variation of several pro- and anti-inflammatory markers after supplementation suggests that lemon verbena extracts may affect cytokine profiles in multiple sclerosis. Further investigation on dietary components with antioxidant and anti-inflammatory properties may contribute to understand MS pathogenesis and ameliorate MS symptoms.

7 comments:

  1. Me thinks that real research is thin on the ground at the moment. May put this lemon stuff on my pancake next Tuesday. Any change of a clinicspeak post on any of the following: the most interesting clinical trial results which will be reporting in the next 18 months, a summary of repair trials underway and future prospects for repair, where we are with neuroprotection and when we may start to see therapies available. I know much of this is guesswork, personal opinion etc. but I (and I suspect others) sometimes need a bit of hope for the future. Many thanks.

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    1. Clinical studies involving a number of potentially useful medications are already under way on the basis of this new data. The results will not be known for at least five years, however, explains Lassmann: "I firmly believe that in the foreseeable future, so within the next five to ten years, we will be successful in fighting the amplification mechanisms and slowing down the progressive phase further." This is from Dr. Hans Lassmann and Dr. Bruce Trapp preeminent researchers in the field of MS pathology.http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(14)70256-X/abstract. Because the research on progression is ongoing don't expect anything for 5-10 yrs: see you in 2020-2025 :-(

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    2. Are the docs living in a dream world?

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    3. probably.

      I have a lemon verbena that I borrowed (a cutting) from stately home garden, It is named after my Australian friend who was with me at the time. A bit of rooting powder and bobs your uncle....a plant that smells like lemon....and a cure for MS? I think not

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  2. "They business people will being say the anti-inflammatory market in MS is saturated and with small molecules off-patent, or due to come off patent, the market will be much less competitive. I predict that Pharma will say no thanks and the academics will be depressed that they have dedicated 15 years of their research careers to a project that has not be commercialised. Why am I so negative? It is simple, almost all new activity in the MS anti-inflammatory field is with repurposed or me-too drugs; i.e. a low-risk strategy." Very true Dr. G, the market for anti-inflammatories in MS is saturated. Therapies targeting neurodegeneration pathways need to take center stage.

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    1. Totally agree about neurodegeneration/neuroprotectants taking centre stage. This is happening, It's the primary focus in our group. Watch this space!

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  3. Ok, I agree that the focus of the pharmaceutical industry are possible ways to repair the myelin and also neuroprotective substances. However I think that one should rather invest in a new generation of anti-inflammatory, since according to the study led by Lassmann et al is the inflammatory process that drives the EM including neurodegeneration, including perhaps a substitute for corticosteroids for pulse therapies. .. And why would be absurd to find a potentially anti inflammatory substance in plants or fungi? ... We do not know even one-third of the planet's biodiversity has to offer ... This to me does not sound absurd because I know this is the history of Aspirin, and what about the Fingolimode which is obtained from a fungus ... Well I just think, who am I to find something ...

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