Valproic Acid

[monkeybus]

I've just persuaded my neurologist to prescribe me some Valproic Acid. Surprisingly easy, but he'd just said no to Tysabri . Think he just wanted me out of the room .

. m.hmg.oxfordjournals.org/co...

Valproic acid induces antioxidant effects in X-linked adrenoleukodystrophy

A specific HDAC inhibitor is Valproic acid (VPA), which is a class I-selective HDAC inhibitor

with anticonvulsive (anti-seizure) effects and thus widespread clinical use in the treatment

of epilepsy. It is a drug that can easily pass the blood-brain barrier, a mechanism which is

hard to achieve in many neurological pharmaceuticals, and has been suggested to provide

neuroprotection both in laboratory tests (In vitro) and also in clinical trials within humans

too.

Previous studies have denoted that within primary cultures of rat corticol neurons the

ABCD2 gene, as discussed in he previous section, was denoted to be responsive to VPA,

strongly up-regulating the gene.

VPA is rapidly metabolized in the liver of mice, so no preclinical studies have been denoted

in ALD mice (knock-out mice; ABCD1-/-

) models. Instead, as VPA has been previously

shown to act as an epileptic drug, a small clinical trial focusing on five X-ALD patients was

performed by Forcade et al. (2010). 40mg/kg VPA (trade name: Depakine) was

administered orally each day for six-months, without causing any denoted side-effects.

Although ABCD2 levels were only slightly increased, and the elevated concentrations of

VLCFAs were not corrected, it was denoted that oxidative damage completely normalized

by the end of the treatment. These results suggest that the drug induced antioxidant

effects in X-ALD patients, which therefore could be of benefit to patients, particularly those

with AMN.

In other news, I'm seeing an endocrinologist next week, then I'm getting botox injections and a Baclofen pump in January .

aldlife.org/wp-content/uplo...

[deengo]

Thanks for posting this Monkey. I have a appointment with my neurologist tomorrow . it's been over a year since I've seen her. I'm going to see if she will prescribe me monafidinal...or how ever you spell it ...and also switch my soma to Valium. I'm also going to read a bunch of post on here tonight so I have lots of questions tomorrow

[monkeybus in reply to deengo]

Go easy on that Valium deengo , very moreish. I switched to it when I tried to get off Gabapentin . Addictive is the word. Especially now I don't booze, it's a lovely way to finish the day, and it's as relaxing as hell.

I'm back on the Gabapentin now.

Now mod4all is back up, I'll stick to them for my Modafini. Far too pricey with my insurance. Worth every penny, though.

I'm pinning my hopes on the Baclofen pump next , if only so I can strike it off the list.

Still early days on the Naltrexone , some reports say it is near instantaneous , others say it takes months.

Let us all know how you get on.

[deengo in reply to monkeybus]

Thanks for the info on the Valium . I've been taking soma for years now. one at bedtime. I was reading that the Valium helps pain and with sleep. the pain clinic I go to said the Valium would be a better option than the soma. I'll talk to my neurologist about it tomorrow. anything new out there I should ask her about?

[monkeybus in reply to deengo]

The grass is always greener. I was actually considering asking for some Soma.

For my money, Lyrica is by far and away the best spasm/pain medication on general prescription. Valium , I can take or leave. It doesn't even stop spasms adequately for me.

Just finished a month long Gabapentin detox, it will be a blessed relief to drift off to sleep tonight. Zero spasms, guaranteed.

[SongStream]

Monkey, thanks for this.

The authors in this abstract say that further clinical investigation is warranted but that was six years ago. Has this study progressed further?

[BMDproductions]

the use of valproic acid sounds very promising

which drug brand are you using? (I think there are various types of valproic acid

[monkeybus in reply to BMDproductions]

I'll know when I collect the meds , think it's Depakine . Let's face it, not too much ongoing research with our disease, full-stop

[BMDproductions]

it could be very effective, I was in touch with the people doing the research about 10 years ago, before they did this study. I didn't know that they had gone ahead. I'm very curious to see how you do. Again, it might be very, very helpful. Also, one other thing: if Depakine causes side effects, (for some it will, for others it won't), apparently there are different variations of valproic acid, so you want to switch brands

[BMDproductions]

typo in last sentence: should read: you may want to switch brands

[wilburlois15]

very interesting article, thanks. Aside from the work on VPA, it nicely explains why they think Lorenzo's oil doesn't work despite the observation that it reduces plasma VLCFA levels

[monkeybus]

The are quite a few candidates for upregulating ABCD2.

I bought some Metformin from mod4all, that site really is great.

ncbi.nlm.nih.gov/pubmed/268...

Spoke to my neurologist about Metformin today. Biggest danger is lowering your blood sugar. I'm going to take it under his supervision.

And, I'm waiting on Caffeic acid phenethyl ester.

ncbi.nlm.nih.gov/pubmed/233...

If it is humanly possible to upregulate my ABCD2, then I'm giving it my best shot.

I'm looking at remyelination as well.

Sick and tired of feeling sick and tired.

All the above + Antioxidants + Mitochondrial nutrients (CoQ10, PQQ, MitoQ, C60 oil).

I am just getting started here.

[monkeybus]

Just taken my first Valproic Acid (Depakine, 200mg). Someone say a prayer for me.

[monkeybus]

I have posted this link before, but I do like to repeat myself.

ncbi.nlm.nih.gov/pmc/articl...

Here is a copy/paste of the relevant bit..

Valproic acid (VPA)

The short-chain fatty acid VPA is a class I-selective HDAC inhibitor with anticonvulsant effects and thus widespread clinical use in treatment of epilepsy. It is well tolerated and passes the blood–brain barrier. VPA provides neuroprotective effects in vitro and clinical improvement in spinal muscular atrophy patients (38). Exposure to VPA induces extensive changes in the transcriptome. More than a thousand genes were identified by microarray analysis as being VPA-responsive in the liver of mice after subchronic oral treatment (56); interestingly, among many genes involved in cholesterol and fatty acid metabolism, including Abcd2, Pex11a, Acox, and several elongases (Elovls) were noticed. Of interest for neurodegenerative aspects, also in a study of primary cultures of rat cortical neurons Abcd2 emerged as responsive (strongly upregulated) to VPA (32).

In a recent study, Pujol and coworkers evaluated the neuroprotective potential of VPA in X-ALD, particularly targeting AMN (31). The authors showed that VPA induces expression of ABCD2 in human X-ALD fibroblasts via inhibition of HDAC, and that oxidative lesions to proteins are significantly reduced by VPA. Thus, it was expected that VPA should reduce VLCFA levels as well. However, whereas C26:0 was not significantly altered, C26:1 was partially reduced in human X-ALD fibroblast. In the spinal cord of X-ALD mice, overexpression of ABCD2 corrects VLCFA levels and the late-onset neurological phenotype (85) and in mice with targeted deletions of both Abcd1 and Abcd2, overexpression of murine ABCD2 protein prevents oxidative damage. Although VPA induced Abcd2 expression in hippocampal slice cultures from rat and mouse (wild-type and Abcd1-deficient), as well as in human cortical slices, the accumulation of saturated (C26:0) VLCFA could not be rescued by VPA in Abcd1 or Abcd1/Abcd2 double-deficient slice cultures. Only mono-unsaturated (C26:1) was partially reduced in the single but not in the double-knockout preparations. As a possible explanation for the discrepancy between induction of ABCD2 and the lack of effect on saturated VLCFA levels, it could be demonstrated that the mRNA levels of several elongase genes (ELOVL3, ELOVL4 and ELOVL5) are elevated by VPA in human X-ALD fibroblast (31). As the corresponding enzymes are involved in chain-length elongation during fatty acid synthesis, their increased expression could generate more VLCFA and, thus, counteract the increase in degradation recruited by elevated ABCD2.

Clinical trial of VPA in human X-ALD patients

Because VPA is metabolized very quickly in the liver of mice, no preclinical study was carried out in the mouse model. Instead, as VPA is a well-established and well-tolerated medication, a small clinical trial was performed in five X-ALD patients (31). VPA (Depakine) was administered orally (40 mg/kg/day) for 6 months without side effects. The ABCD2 mRNA levels were slightly increased above baseline in peripheral blood monocytes after 6 months, but the elevated concentrations of VLCFA (both C26:0 and C26:1ω9) were not corrected. However, the markers for oxidative damage were completely normalized or strongly reduced at the end of treatment. These results suggest that VPA induces antioxidant effects in X-ALD, which could be of significant benefit especially for patients with AMN (31).

My pills are 200mg, but this study says 40 mg/kg/day. I weigh in at a slender 60kg, that would make for 2400mg daily.

My neurologist did say I could up my dose. I am seeing him again next month. See what he says.

Also, it's early days, but I like the LDN. Maybe I'm just going through a low-spasticity phase, maybe it's the LDN. Either way, I feel good.

Take care, folks. We should all post more