Van Joan: [URL="http://ccsviinms.blogspot.fi/2015/05/ne ... ilast.html"][U]"Neuroprotection" and Ibudilast[/U][/URL]
[QUOTE]What MS researchers are now doing is working with pharmaceutical companies to test and prescribe new drugs which address the damage caused by slowed blood flow. And these drugs are called "neuroprotective."
Which is exactly what Dr. Robert Fox is doing now with Ibudilast.
How does ibudilast work?
It relaxes blood vessels and increases blood flow by inhibiting phosphodiesterases and releasing nitric oxide from the endothelium.[/QUOTE]
[QUOTE]Dr. Fox has been working on a clinical trial for those with progressive MS, using Ibudilast (MN-166) which has been prescribed to treat stroke and asthma patients for two decades-[/QUOTE]
[QUOTE]When Dr. Zamboni discovered the link to slowed venous return, hypoperfusion and MS, he opened up a new way of looking at the MS disease process. Although neurologists and MS specialists will not say this, he has changed how they are studying the MS disease process and how they are developing drugs to treat MS.
And, not coincidently, one such researcher is Dr. Robert Fox. In 2010, Dr. Fox, a neurologist, received money from the MS Society to study CCSVI, a vascular disorder. A medical student in his lab discovered never before seen venous malformations in the jugular veins of cadavers of people with MS. And in 2011, the results of this study cause quite a stir at ECTRIMS.[/QUOTE]
[QUOTE]"Hemodynamic consequences from intraluminal abnormalities" simply means they found a mechanical reason for the slowed blood flow, also known as hypoperfusion, which exists in MS. Blockages inside the veins.
This hypoperfusion and ischemia in MS is a fact. But neurologists and MS specialists cannot make any money treating venous malformations, or understanding how to improve perfusion with nutrition, exercise and lifestyle adjustments. Understanding the heart brain connection won't benefit them, or their labs. [/QUOTE]
Ibudilast
-
Marsei
Ibudilast sprints to the lead and shows success in progressive MS
Ibudilast sprints to the lead and shows success in progressive MS
Late Breaking ECTRIMS News. [URL="http://multiple-sclerosis-research.blog ... ilast.html"][U]Ibudilast[/U][/URL] sprints to the lead and shows success in progressive MS
[QUOTE]Earlier in the year [URL="http://multiple-sclerosis-research.blog ... -news.html"][U]I expressed concern[/U][/URL] about the use of Ibudilast in MS.
The wait is over and I was possibly wrong,
It was shown that Ibudilast reduced brain volume loss by 48%. in progressive MS, so supporting the past trial in MS. As we know this agent does not stop relapses and so now the age of progressive MS really changes.
Probably as ProfG says below...we don't know if this effect was clinically meaningful, but at least it's a start.[/QUOTE]
Late Breaking ECTRIMS News. [URL="http://multiple-sclerosis-research.blog ... ilast.html"][U]Ibudilast[/U][/URL] sprints to the lead and shows success in progressive MS
[QUOTE]Earlier in the year [URL="http://multiple-sclerosis-research.blog ... -news.html"][U]I expressed concern[/U][/URL] about the use of Ibudilast in MS.
The wait is over and I was possibly wrong,
It was shown that Ibudilast reduced brain volume loss by 48%. in progressive MS, so supporting the past trial in MS. As we know this agent does not stop relapses and so now the age of progressive MS really changes.
Probably as ProfG says below...we don't know if this effect was clinically meaningful, but at least it's a start.[/QUOTE]
-
Marsei
Hot Topic at the ECTRIMS Late Breaking News
Hot Topic at the ECTRIMS Late Breaking News
De [URL="http://multiple-sclerosis-research.blog ... -news.html"][U]blog[/U][/URL] waar naar verwezen wordt: Hot Topic at the ECTRIMS Late Breaking News
Dit was eerder uit [URL="https://www.ncbi.nlm.nih.gov/pubmed/20200338"][U]onderzoek van de VU[/U][/URL] gebleken:
[QUOTE][B]CONCLUSION[/B]:Ibudilast showed no beneficial effect on the rate of newly active lesions and relapses. However, preliminary evidence suggests that ibudilast seems to act in a neuroprotective fashion as measured by 2 independent MRI outcomes, with a possible beneficial clinical effect on disability progression.[/QUOTE]
[URL="https://www.ncbi.nlm.nih.gov/pubmed/27521810"][U]Onderzoek Fox[/U][/URL]:
[QUOTE][B]Background[/B]: Primary and secondary progressive multiple sclerosis (MS), collectively called progressive multiple sclerosis (PMS), is characterized by gradual progression of disability. The current anti-inflammatory treatments for MS have little or no efficacy in PMS in the absence of obvious active inflammation. Optimal biomarkers for phase II PMS trials ares unknown. Ibudilast is an inhibitor of macrophage migration inhibitor factor and phosphodiesterases-4 and -10 and exhibits possible neuroprotective properties. The goals of SPRINT-MS study are to evaluate the safety and efficacy of ibudilast in PMS and to directly compare several imaging metrics for utility in PMS trials.
[B]METHODS[/B]:SPRINT-MS is a randomized, placebo-controlled, phase II trial of ibudilast in patients with PMS. Eligible subjects were randomized 1:1 to receive either ibudilast (100mg/day) or placebo for 96 weeks. Imaging is conducted every 24 weeks for whole brain atrophy, magnetization transfer ratio, diffusion tensor imaging, cortical brain atrophy, and retinal nerve fiber layer thickness. Clinical outcomes include neurologic disability and patient reported quality of life. Safety assessments include laboratory testing, electrocardiography, and suicidality screening.
[B]RESULTS[/B]:
A total of 331 subjects were enrolled, of which 255 were randomized onto active study treatment. Randomized subjects were 53.7% female and mean age 55.7 (SD 7.3) years. The last subject is projected to complete the study in May 2017.
[B]CONCLUSION[/B]:
SPRINT-MS is designed to evaluate the safety and efficacy of ibudilast as a treatment for PMS while simultaneously validating five different imaging biomarkers as outcome metrics for use in future phase II proof-of-concept PMS trials.[/QUOTE]
[QUOTE]So there you have it. It looks like anti-TNF can exacerbate MS (There is plenty more evidence from arthritis studies with anti-TNF), and PD4 inhibitors block TNF, so PDE4-inhibition in MS is a good thing? It couldn't make MS worse? Could it?[/QUOTE]
[QUOTE]So based on selective vision of animal models, a trial was done and it was stopped because of a sense of worsening. Rolipram really didn't work as an immunomodulator in relapsing EAE, so failed in RR, just as did Ibudilast did (see above). So don't blame the animals.
So what's going to happen when it is used progressive MS, which is not noted for its MRI activity. Hopefully no worsening but anti-TNF has been tried in SPMS[/QUOTE]
[QUOTE]So anti-TNF in SPMS did nothing (didn't make things better)...is this the exception of the rule? We will soon find out. I really hope it is not, but.......[/QUOTE]
[QUOTE]So two PDE inhibitors make MS worse, should a third have been tried?
Too late now, just as it probably was when I aired my concerns about this in March 2015
But if it bad news in Paris 2017, you now know why.
If it isn't, is it luck or Good Design?
However, I need to say now the fact that the study by Barkof et al. 2010 was not associated with worsening and is was a large trial and no worsening was reported, which is a good thing and may serve to ease my concerns
Ibudilast (AV111, MN-166) is a drug that has been used for the treatment of asthma in Japan for about 20 years and has been taken by millions of people. [/QUOTE]
De [URL="http://multiple-sclerosis-research.blog ... -news.html"][U]blog[/U][/URL] waar naar verwezen wordt: Hot Topic at the ECTRIMS Late Breaking News
Dit was eerder uit [URL="https://www.ncbi.nlm.nih.gov/pubmed/20200338"][U]onderzoek van de VU[/U][/URL] gebleken:
[QUOTE][B]CONCLUSION[/B]:Ibudilast showed no beneficial effect on the rate of newly active lesions and relapses. However, preliminary evidence suggests that ibudilast seems to act in a neuroprotective fashion as measured by 2 independent MRI outcomes, with a possible beneficial clinical effect on disability progression.[/QUOTE]
[URL="https://www.ncbi.nlm.nih.gov/pubmed/27521810"][U]Onderzoek Fox[/U][/URL]:
[QUOTE][B]Background[/B]: Primary and secondary progressive multiple sclerosis (MS), collectively called progressive multiple sclerosis (PMS), is characterized by gradual progression of disability. The current anti-inflammatory treatments for MS have little or no efficacy in PMS in the absence of obvious active inflammation. Optimal biomarkers for phase II PMS trials ares unknown. Ibudilast is an inhibitor of macrophage migration inhibitor factor and phosphodiesterases-4 and -10 and exhibits possible neuroprotective properties. The goals of SPRINT-MS study are to evaluate the safety and efficacy of ibudilast in PMS and to directly compare several imaging metrics for utility in PMS trials.
[B]METHODS[/B]:SPRINT-MS is a randomized, placebo-controlled, phase II trial of ibudilast in patients with PMS. Eligible subjects were randomized 1:1 to receive either ibudilast (100mg/day) or placebo for 96 weeks. Imaging is conducted every 24 weeks for whole brain atrophy, magnetization transfer ratio, diffusion tensor imaging, cortical brain atrophy, and retinal nerve fiber layer thickness. Clinical outcomes include neurologic disability and patient reported quality of life. Safety assessments include laboratory testing, electrocardiography, and suicidality screening.
[B]RESULTS[/B]:
A total of 331 subjects were enrolled, of which 255 were randomized onto active study treatment. Randomized subjects were 53.7% female and mean age 55.7 (SD 7.3) years. The last subject is projected to complete the study in May 2017.
[B]CONCLUSION[/B]:
SPRINT-MS is designed to evaluate the safety and efficacy of ibudilast as a treatment for PMS while simultaneously validating five different imaging biomarkers as outcome metrics for use in future phase II proof-of-concept PMS trials.[/QUOTE]
[QUOTE]So there you have it. It looks like anti-TNF can exacerbate MS (There is plenty more evidence from arthritis studies with anti-TNF), and PD4 inhibitors block TNF, so PDE4-inhibition in MS is a good thing? It couldn't make MS worse? Could it?[/QUOTE]
[QUOTE]So based on selective vision of animal models, a trial was done and it was stopped because of a sense of worsening. Rolipram really didn't work as an immunomodulator in relapsing EAE, so failed in RR, just as did Ibudilast did (see above). So don't blame the animals.
So what's going to happen when it is used progressive MS, which is not noted for its MRI activity. Hopefully no worsening but anti-TNF has been tried in SPMS[/QUOTE]
[QUOTE]So anti-TNF in SPMS did nothing (didn't make things better)...is this the exception of the rule? We will soon find out. I really hope it is not, but.......[/QUOTE]
[QUOTE]So two PDE inhibitors make MS worse, should a third have been tried?
Too late now, just as it probably was when I aired my concerns about this in March 2015
But if it bad news in Paris 2017, you now know why.
If it isn't, is it luck or Good Design?
However, I need to say now the fact that the study by Barkof et al. 2010 was not associated with worsening and is was a large trial and no worsening was reported, which is a good thing and may serve to ease my concerns
Ibudilast (AV111, MN-166) is a drug that has been used for the treatment of asthma in Japan for about 20 years and has been taken by millions of people. [/QUOTE]