leriglitazone

[JShough]

Hi! 39 years old now and still symptom free without walking issues although I do get heavy feeling legs and my muscles feel strange in them in the mornings. I have been having mris every couple of years since 2005 and they've never picked up anything. On my last MRI there is still no involvement on the spine but they found a cerebral change in the area they would expect ALD to be. I have seen the scan and it is a tiny affected area, they showed me other scans that look wildy different from other ALD patients. I had a follow up contrast dye MRI and they had a quick look at it on Friday but couldn't see anything additional to worry about. I've taken Lorenzos oil for years but they don't know if it's helped or not. My doctor at addenbrookes has asked for compassionete access to leriglitazone and the company has said yes I believe, I just need to travel to London for a chat and assessment and to see what they will require from me. The data looks good for halting cerebral change. Has anyone else been on the drug at all and can provide feedback? I know the trial they previously did was looking to try and help people who had ALD on their spine and it failed as a trial for this but they discovered that ir stopped brain changes. I will stop taking Lorenzos oil and hopefully start on this drug soon all being well and not running into any roadblocks but anything anyone else can add on things would be greatly appreciated. Many thanks. Justin

[3WheelWonder]

Justin, you’re doing fucking awesome. Why are you even looking at getting drugs? And on the MRI: why do you keep getting them? I’ve always wondered that with AMN patience, because the only option is a BMT, and that’s basically an an option for adults.

[JShough in reply to 3WheelWonder]

My doctor said it's either get the drugs, do nothing or have a BMT. I don't want a BMT because of all the risks and it may not work. Always had the MRIs out of my own curiosity and that of the doctors who look after me. I don't want to get worse in 5-10 years time or 10-15 etc so if the drug will keep me as I am it's tempting, but they don't actually know if I'll get any worse or what will happen, they literally can't advise on what could happen, but I feel going on the drug if it does have minimal side effects could make a lot of sense if it helps protect my future. It's a lot to think about though.

[3WheelWonder in reply to JShough]

got it.

[monkeybus in reply to JShough]

Smooth work. Plainly you have a decent, forward thinking doctor.

The fact that barely any of us adults take Lorenzo's or mustard oil speaks volumes for it's efficacy. Leriglitazone is a different matter. The science is really coming in on this one.

Leriglitazone Treatment May Slow Progression of Adrenomyeloneuropathy

practicalneurology.com/news...

The brain penetrant PPARγ agonist leriglitazone restores multiple altered pathways in models of X-linked adrenoleukodystrophy

pubmed.ncbi.nlm.nih.gov/340...

Several years ago, I asked my neurologist for Metformin.

Metformin-induced mitochondrial function and ABCD2 up-regulation in X-linked adrenoleukodystrophy involves AMP-activated protein kinase

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

Good results from the clinical trials. I left it with my neurologist to mull over and never chased it up.

I am not in the UK right now, but the drug Pioglitazone is widely available and has shown excellent results.

Pioglitazone halts axonal degeneration in a mouse model of X-linked adrenoleukodystrophy

pubmed.ncbi.nlm.nih.gov/237...

Here is a comparison of the two drugs suggesting that Leriglitazone is effective for our disease at lower dosages than Pioglitazone

The brain penetrant PPARγ agonist leriglitazone restores multiple altered pathways in models of X-linked adrenoleukodystrophy

science.org/doi/10.1126/sci...

I am seeing my neurologist next week, I'll have a serious talk with him about this.

[JShough in reply to monkeybus]

Thanks for your response. The more I read about the drug the more I think it could be very important and potentially life changing for many people. Let's hope so.

Karen from Alex TLC sent me this link earlier; labiotech.eu/trends-news/mi...

[cfox]

I'm sure what you're going through is very scary, but the good news is that leriglitazone seems very promising for someone in your situation.

Minoryx finally published the results of the leriglitazone study in a peer-reviewed journal this month. They provided more details than had previously been released.

sciencedirect.com/science/a... (it used to be available for free but now it seems like it's behind a paywall)

0 out of 77 patients on leriglitazone showed new or growing cerebral lesions

6 out of 39 patients on the placebo showed new or growing cerebral lesions

Here's what happened with the six who were taking the placebo who did show evidence of cerebral disease (it's buried in the supplemental materials, on page 9):

Patient 1: got BMT, but died of complications from the transplant

Patient 2: got BMT, lesions stabilized

Patient 3: switched from placebo to leriglitazone for 12 months, lesions stabilized

Patient 4: switched from placebo to leriglitazone, but dropped out after 3 months because of adverse events (presumably swelling/edema).

Patient 5: switched from placebo to leriglitazone for 12 months, lesions stabilized

Patient 6: switched from placebo to leriglitazone for 12 months, lesions stabilized

So 2 got a BMT, one died and one survived

All 3 who took leriglitazone for 12 moths did pretty well.

So it's great that you are getting access to leriglitazone. Good luck!

[JShough in reply to cfox]

Thanks ever so much, yes the more I read up on it the more I can see just how positive everything around it is. I feel very fortunate I may have the chance to go onto the drug.

[JShough]

As an update to this, I went to London and met Doctor Robin Lachmann. He is going to start me on the drug soon then I will need to go bk to London after being on it for 4 weeks so they can tweak the dosage. He views this more of a temporary solution though and I think has concerns over just how well it could work long term. He says at 39 being fit and healthy and basically symptom free with a loes score of just 5 he feels I am prime candidate for bone marrow transplant. To say I am worried about this is an understatement. What are peoples thoughts on this and the transplant in general? I've been speaking to someone who had it done successfully and is now cured and doesn't need to worry about brain side of things. But he took a year to get over having it done and it was 7 years ago and his life is still changed from it with certain dietary requirements. My sick pay at work doesn't cover pre existing medical conditions so wouldn't cover me for this so I'm worried about things financially also. Any advice or guidance will be appreciated. I am hoping to meet with transplant team soon to get full fact's and discuss before any decisions thanks