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Mitochondrial dysfunction linked to neurodegeneration


Senior Member
Premission to repost by Prof.Gavin Giovannoni

There are some in the ME/CFS medical field that believe ME/CFS is 'MS Light' or 'Atypical MS'. The reason I post these articles is the fact that research in one area may spill over into another area of research or the fact that researchers reviewing a site may look at the research in another disease category that could be related to theirs and it might raise their interest level.

Mitochondrial dysfunction linked to neurodegeneration in MS

"Energetics; the new buzz word in MS. There is mounting evidence that malfunction of mitochondria contributes to neurodegeneration in MS. The mitochondria are the energy factories of the cells and generate much needed energy for nerve conduction and to maintain the integrity of axons and neurons.

In addition, mitochondria have the ability to signal to the cell to commit suicide. When mitochondria are not working very well the cell has to generate energy without using oxygen. This results in the production of lactic acid.

The study below shows that lactic acid detected in the peripheral blood of MSers correlates with neurodegeneration in the retina. The investigators imply in their conclusions that this may be causal, i.e. the mitochondrial dysfunction may be causing the neurodegeneration.

Playing devil's advocate it may be the other way round; could neurodegeneration be causing mitochondrial dysfunction?

As cells die they trigger local innate immune reactions via complex cell sensing mechanisms. Some of these mechanisms produce mediators that then lead to secondary mitochondrial dysfunction. This is called reverse causation. To dissect out these two hypotheses we need to treat MS with drugs that enhance mitochondrial function or protect them and see if it improves MS and/or delays MS disease progression. In fact we have included a novel drug class in our recent funding application to the progressive MS alliance."

Epub: Petzold et al. Visual pathway neurodegeneration winged by mitochondrial dysfunction. Ann Clin Transl Neurol. 2015;2(2):140-50. doi: 10.1002/acn3.157.

To test for structural and functional contribution of mitochondrial dysfunction to neurodegeneration in multiple sclerosis (MS). A visual pathway model void of MS lesions was chosen in order to exclude neurodegeneration secondary to lesion related axonotmesis.

A single-centre cohort study (230 MS patients, 63 controls). Spectral domain optical coherence tomography of the retina, 3T magnetic resonance imaging of the brain, spectrophotometric assessment of serum lactate levels. Postmortem immunohistochemistry.

The visual pathway was void of MS lesions in 31 patients and 31 age-matched controls. Serum lactate was higher in MS compared to controls (P = 0.029). High serum lactate was structurally related to atrophy of the retinal nerve fiber layer at the optic disc (P = 0.041), macula (P = 0.025), and the macular ganglion cell complex (P = 0.041). High serum lactate was functionally related to poor color vision (P < 0.01), Expanded Disability Status Scale score (R = 0.37, P = 0.041), Guy's Neurological disability score (R = 0.38, P = 0.037), MS walking scale (R = 0.50, P = 0.009), upper limb motor function (R = 0.53, P = 0.002). Immunohistochemistry demonstrated increased astrocytic expression of a key lactate generating enzyme in MS lesions as well as profound vascular expression of monocarboxylate transporter-1, which is involved in lactate transport.

This study provides structural, functional, and translational evidence for visual pathway neurodegeneration in MS related to mitochondrial dysfunction.

Mitochondria again, but this time in muscle!
Pathol Res Pract.2015 Feb 17. pii: S0344-0338(15)00027-8. doi: 10.1016/j.prp.2015.02.004. [Epub ahead of print]Skeletal muscle findings in experimental autoimmune encephalomyelitis.
Luque E, Ruz-Caracuel I, Medina FJ, Leiva-Cepas F, Agüera E, Sánchez-López F, Lillo R, Aguilar-Luque M, Jimena I, Túnez I,Peña J.

Skeletal muscle is a target organ in multiple sclerosis, a chronic debilitating disease of the central nervous system caused by demyelination and axonal deterioration.

Since the experimental autoimmune encephalomyelitis model reproduces the relapsing-remitting course found in most multiple sclerosis patients, this model was used to compare the histological features of skeletal muscle at onset with those observed at the start of the second relapse.

Histological, histochemical and ultrastructural changes, as well as biochemical oxidative damage and antioxidant-system markers, were examined in the soleus and extensor digitorum longus muscles of Dark Agouti rats in which experimental autoimmune encephalomyelitis had been induced by active immunization using myelin oligodendrocyte glycoprotein.

Histological examination at disease onset revealed ragged-red fibers and ultrastructural evidence of mitochondrial degeneration. At the second relapse, neurogenic changes included a wide range of cytoarchitectural lesions, skeletal muscle atrophy and the appearance of intermediate fibers; however, differences were observed between soleus and extensor digitorum longus lesions. Biochemical tests disclosed an increase in oxidative stress markers at onset, which was more pronounced at the second relapse.

Microscopic findings suggest that two patterns can be distinguished at disease onset: an initial phase characterized by muscle mitochondrial alterations, and a second phase dominated by a histological muscle pattern of clearly neurogenic origin.

This is work done in the mouse model of MS (the EAE model), and some caution should be exercised when drawing parallels with humans and with MS as a whole.

Nonetheless, these findings raise interesting questions about whether the same happens in MSers? I've sometimes wandered about this in clinic, particularly in those with disproportionate muscle wasting, in so far as to send some of them to a neurophysiologist for EMGs! [In general terms were are taught that muscle wasting is a late feature of CNS disorders but seen early in peripheral nervous system disorders, including muscle disease].

But the researchers here demonstrate three fundamental facts:
1) That the muscle is affected in the acute phase i.e. onset of the EAE disease - equivalent to a human relapse, and the changes that take place are almost exclusively related to mitochondrial dysfunction;
2) it's only at the mid-to-longterm disease phase that the muscle changes point to changes that are neurogenic in origin, i.e. caused by denervation of the muscle (from lack of axons); and
3) mitochondrial damage is linked to an increase in oxygen reactive species production (i.e. oxidative stress), which is driving force for destruction of the denervated skeletal muscle over the long-term.

Could Co-enzyme Q10 supplementation therefore become a future addition to the steroid armamentarium in an MS relapse??



Senior Member
Logan, Queensland, Australia
When I was being taught about mitochondrial disease at university circa 2000-2 it was already established that mitochondrial dysfunction can cause neurological damage, and usually started rising in severity in a patient over 40 as normal aging, wear and tear combined with the deficit. The example cited was inherited hearing loss. What we are slowly learning is that this may apply to many more diseases than at first thought. There is no question that ME has a major problem with mitochondrial function, but it has yet to be established that the primary cause is inside the mitochondria. It could be something else affecting the mitochondria.


Senior Member
If this is right it could help explain why treating us as depressed has been harmful and other treatments might also be helping cause the fatigue. He says antidepressants, antibiotics and analgesics all damage mitochondria.
Does anybody know how to get a mito-atp profile test

see http://drmyhill.co.uk/wiki/Mitochon...r_overseas_CFS_sufferers_-_how_to_get_it_done
I requested this test from Dr Myhill in UK -here is response:
Dear Kevin
Many thanks for your email. I am sorry but at present we are unable to accept any requests for Mitochondrial Function testing due to Dr Myhill's overwhelming workload. This situation is unlikely to alter for the foreseeable future. I have copied the last announcement from the website for your information :


♦ All test interpretations, and test orders, including the Mitochondrial Function Test, have now been suspended for "new patients" until further notice. This is due to my excessive workload. Please watch this space for news of when testing is likely to be resumed. You are deemed a "new patient" if you have never received advice from me before (by way of a face-to-face or a telephone consultation, or a letter of advice based on a questionnaire, or an interpretation of your test results). Current patients can access my advice and tests in the usual way."
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Senior Member
@kaband2015 There are other practitioners in the UK who work in a similar way to Dr Myhill and somewhere on her site is a list of them as she has been involved in training them. This means that some of them at least are able to access Acumen Lab where this test is done. I know this because I had the test done myself via one of them (Dr Charles Forsyth).

Here is the link to the list...http://drmyhill.co.uk/wiki/Practitioners_trained_to_treat_CFS

I don't know if you are in the UK or abroad, but maybe some of them do consultations via Skype or phone, and you can email first to make sure that they use the Acumen Lab's Mito Function Test as this is the only lab that does it in the UK.
I am in USA and you must be in UK that is a great idea I will google -if you have knowledge of contact info for dr forsyth or other practitioners who can facilitate please send you can also email me at k.feldman@comcast.net thnk you for that info I don;t care if I have to fly there I need that test done regards