Pioglitazone

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Pioglitazone

Postby MacGyver » Wed Aug 04, 2004 1:44 am

The substance used for treating diabetes mellitus type II, Pioglitazone, previously mentioned here on thisisms.com, has been tested on a single patient for three years. The patient had secondary progressive MS. The study concludes that "MRIs carried out after 10 and 18 months of treatment showed no perceptible change in overall brain atrophy, extent of demyelination, or in Gd-enhancement. After 3.0 years on pioglitazone, the patient continues to be clinically stable, with no adverse events"

I think this is highly interesting. The dosage used was equal to the dosage used for diabetes.

The article previously written on thisisms.com about a larger trial can be found here.

Supplying the Pubmed abstract as is:
BACKGROUND: Ligands of the peroxisome proliferator-activated receptor-gamma (PPARgamma) induce apoptosis in activated T-lymphocytes and exert anti-inflammatory effects in glial cells. Preclinical studies have shown that the thiazolidinedione pioglitazone, an FDA-approved PPARgamma agonist used to treat type 2 diabetes, delays the onset and reduces the severity of clinical symptoms in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis (MS). We therefore tested the safety and therapeutic potential of oral pioglitazone in a patient with secondary MS. CASE PRESENTATION: The rationale and risks of taking pioglitazone were carefully explained to the patient, consent was obtained, and treatment was initiated at 15 mg per day p.o. and then increased by 15 mg biweekly to 45 mg per day p.o. for the duration of the treatment. Safety was assessed by measurements of metabolic profiles, blood pressure, and edema; effects on clinical symptoms were assessed by measurement of cognition, motor function and strength, and MRI. Within 4 weeks the patient exhibited increased appetite, cognition and attention span. After 12 months treatment, body weight increased from 27.3 to 35.9 kg (32%) and maintained throughout the duration of the study. Upper extremity strength and coordination improved, and increased fine coordination was noted unilaterally after 8 months and bilaterally after 15 months. After 8 months therapy, the patient demonstrated improvement in orientation, short-term memory, and attention span. MRIs carried out after 10 and 18 months of treatment showed no perceptible change in overall brain atrophy, extent of demyelination, or in Gd-enhancement. After 3.0 years on pioglitazone, the patient continues to be clinically stable, with no adverse events. CONCLUSIONS: In a patient with secondary progressive MS, daily treatment with 45 mg p.o. pioglitazone for 3 years induced apparent clinical improvement without adverse events. Pioglitazone should therefore be considered for further testing of therapeutic potential in MS patients.
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Postby wilson » Wed Aug 04, 2004 6:17 am

I am curious. 400,000 people in the U.S. has MS. Out of the 400,0000, small portion probably developed type II diabetes and started taking this drug. Is this how they found out that Pioglitazone helped?
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Postby MacGyver » Wed Aug 04, 2004 7:49 am

wilson wrote:I am curious. 400,000 people in the U.S. has MS. Out of the 400,0000, small portion probably developed type II diabetes and started taking this drug. Is this how they found out that Pioglitazone helped?


No it doesn't seem so. Pioglitazone is a fairly new drug on the market. In Europe it has been used for diabetes since 2000. Since this study started in 2001, I doubt that any benifits on MS had been reported at that time.

This particular study was started due to reports that it inhibited EAE in mice. It was tested in EAE because of it's effects on T-cells and anti-inflammatory properties.

Interestingly the authors concluded that the "The beneficial effects of pioglitazone observed in this patient are somewhat unexpected as inflammation is less prominent in secondary progressive MS compared to relapsing remitting disease", which I personally think might suggest other ways of action than via the anti-inflammatory properties. For example, Pioglitazone has been reported to have many beneficial propterties to the vascular system of the human body.

The complete pioglitazone article is available for free access here.
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Postby MacGyver » Tue Aug 10, 2004 6:25 am

Irreversible damage in SPMS yet reversible?
I think it is interesting to discuss a few things, regarding the new treatments which have been reported to have an effect on SPMS. It is especially interesting when the treatment results in reversal of symptoms, like in the case of pioglitazone. Other agents such as LDN (anecdotal) and Aimspro are also reported to have a positive effect on SPMS. What can these new findings possibly tell us about MS as a disease?

Let us make an important assumtion: These agents have some effect in reversing symptoms and halting progression of SPMS.

No one nows for sure why RRMS eventually turns in to SPMS. There are some theories:
A) Axonal damage in RRMS eventually becomes so heavy that the CNS can no longer compensate for the loss, and there is no chance of remission.
B) Chronic inflammation of some kind.
C) Accumulation of dangerous breakdown substances in the brain following years of inflammation.

I'm sure there are more, please remind me!

The woman in the plioglitazone study showed improvement from a very devasted condition within 4 weeks. People on LDN report benefit within days to weeks and patitients on Aimspro have been described as "improving in front of our eyes" etc, also very rapidly.

My main questions:
1) Considering these theories, is reversal of SPMS even theoretically possible? (I believe the answer is no)
2) If not, what does that tell us, if agents like Pioglitazone and Aimspro indeed are reversing symptoms thought to be permenent?

/Mac
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Postby Felly » Tue Aug 10, 2004 3:52 pm

http://www.pubmedcentral.nih.gov/articl ... d=15285797

This article also mentions this one patient. It exames the role of Peroxisome proliferator-activated receptors (PPARs). In particular PPAR-y which regulates insulin and is activated by Pioglitazone. Apparently also by the NSAIDS indomethacin and ibuprofen.

What is also interesting is that PPARs are activated by fatty acids specifically PUFAs.

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Postby finn » Wed Aug 11, 2004 4:58 am

Sorry, time to leave the board.

-finn
Last edited by finn on Sun Aug 28, 2005 9:33 am, edited 1 time in total.
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Postby vk » Wed Aug 11, 2004 10:54 am

:D JUST CURIOS, HAS ANY ONE TRIED OR IS USING THIS 'NEW' TREATMENT? I AM SPMS AND ON NOVANTRONE, THIS, IF IT WORKS, SOUNDS A WHOLE LOT EASIER TO TOLERATE. THE DRS. ARE HAPPY I AM STABLE, BUT I HAVE NEVER RETURNED TO BASELINE AFTER THE LAST EXACERBATION. SOUNDS TOO GOOD TO BE TRUE. LET US KNOW, THANKS, VIKKI :D
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