Albuterol add on therapy

[Cvfactor]

I have been on Copaxone since January 2013 and was doing fine until last month when I started to relapse.

I really don't want to switch to an immunosuppressive drug so I started looking into add on therapies for Copaxone.

I came across a study conducted by Harvard researchers who looked at adding Albuterol which is an asthma drug to Copaxone.

I didn't think much of it until I read the full paper. It seems this combination resulted in a relapse rate of 0.09/year compared to 0.37/year for Copaxone only. I find this amazing and am going to talk to my neuro about it.

Here is a link to the paper:
http://archneur.jamanetwork.com/arti...ticleid=801029

And here is a graph showing the relapses that occurred between the two groups:

[Cvfactor]

beta 2 adrenergic receptors

Albuterol is a beta 2 adrenergic receptor agonists. This type of drug allows the nervous system to control the immune system when it senses over activity of an inflammatory response.

Many immune cells have adrenergic receptors so this may be another avenue which immunity/autoimmunity is controlled.

It looks like this type of drug is being considered for Parkinsons disease along with other neurological disorders.

I think the group from Harvard are way ahead of the game in MS research:

http://www.hindawi.com/journals/jir/2014/103780/

[Apollo]

Thank you so much for both those informative studies, Cvfactor.

There was an 8 year MS trial involving a similar asthma drug suggesting you may be on to something.

Another asthma drug tested in MS is fenoterol. It and albuterol are both “Beta 2 adrenergic receptor antagonists” designed to open up the air passages. These are generally considered to be immunomodulatory rather than immunosuppressive.

Fenoterol was tested in 578 newly diagnosed MSers in Taiwan from Jan 2002 until Dec 2008.

Beta2-adrenergic agonist use and the risk of multiple sclerosis: a total population-based case-control study.
http://www.ncbi.nlm.nih.gov/pubmed/24732071

OBJECTIVE: The aim of this study was to investigate whether the use of fenoterol, a beta2-adrenergic agonist, was associated with multiple sclerosis (MS) risk by conducting a total population-based case-control study in Taiwan.

CONCLUSIONS: The results of this study suggest that fenoterol use may reduce the risk of MS.

Of course, studies to clarify the value of albuterol and fenoterol in MS are not likely to get funded by Pharma. Large trials are very, very, expensive and if a clear path to profitability is not apparent (unable to patent common drugs like these) large trials are not going to happen in the US, IMO. An inexpensive competitor for extremely profitable current therapies isn’t too appealing for Pharma. I wouldn’t count on disease societies, either. They seem attuned to Pharma’s interests and don’t want to offend some of their biggest donors, I suppose. Forgive me for such soberness.

But I am excited about your find, Cvfactor! Down the road you may also want to investigate LDN as a possibility. Your doctor will think you are crazy but always be more interested in your health than he/she or you will always have less good health than what is possible, IMO.

Good work, those studies are interesting and promising!
Best of luck!

[Cvfactor]

Hi Apollo,

I agree that it is not likely that further trials will be conducted on Albuterol, but I'm glad at least a phase 2 study was done for people who wish to pursue it off label.

Reading the abstract of the paper wasn't that impressive but the data was fascinating once you read it in full.

I did read the paper you posted about the incidence of MS and Feternol use and it adds more to the notion of it being effective.

I think it is becoming clear that the nervous system has influence over the immune system and the beta 2 adrenergic receptor plays a role:

http://www.ncbi.nlm.nih.gov/pubmed/21855626

[Cvfactor]

Dosage

One more thing that I should point out about this study. The form of Albuterol was given in a 4mg daily tablet (for asthma it is usually inhaled).

In comparison to the maximum daily dosage of 32mg this is a small amount. There did not seem to be any major problems with this dosage over the two years the trial lasted.

I think it looks like a good alternative to me.

[Cvfactor]

More Studies

Here is another recent study that looks at the Beta2 agonist as it relates to control of the immune system:

http://www.jimmunol.org/content/192/...nt/120.3.short

[Cvfactor]

Here is another brand new article about another asthma medication (solmeterol which is also a beta2 adrenergic receptor agonist) and how it regulates immune cell function:

http://www.sciencedirect.com/science...89159114005637

[Cvfactor]

It looks like arthritis researchers are finding that the sympathetic nervous system not only controls inflammation but can allow a continuously activated state of the immune system to persist uncontrolled which may lead to autoimmunity.

This seems like what happens in multiple sclerosis with acute inflamitory attacks during relapsing disease followed by progressive disease.

Here is an article that describes this. Notice the beta2 adrenergic receptor agonists (which albuterol is a member of) involvement in this process.

http://arthritis-research.com/content/16/6/504

[myoak]

Thanks for the articles and links. Albuterol appears to have good effect in MS and immune system diseases.

[Cvfactor]

I agree. I think many researchers are finding out that the immune system does not function autonomously and the nervous system can intervene to shut down activity.

I would like to see a phase 3 trial on Albuterol but this is not likely to happen.

I did talk to my neuro today about it as on add on therapy.
I think he had the same initial reaction I did (this is an asthma drug?), but he seemed interested in reading the studies I found, and will let me know if he will prescribe it in a few weeks.

[Cvfactor]

Nervous system and immune system interaction

Here is a recent review article describing how the nervous and immune system interact with each other:

http://m.advan.physiology.org/content/38/2/135.full

If you read it you will see that the beta-2 adrenergic receptor is found on many immune cells and activation of this receptor seems to be a way for the nervous system to communicate with the immune system.

Since Albuterol is a beta-2 adrenergic receptor agonist, it makes sense to me that this would have an effect on relapses when added to Copaxone.

[Suebee]

This is really interesting. CVfactor, The article you cited talks about the role the spleen and vagus nerve play in regulating immune response. It states HRV--Vagus nerve activity, is reduced in autoimmune diseasses like RA. The study seems to suggest that modulation of vagus nerve signals may treat disease. Do you think this Could be a possible explanation of why some people found improvement from CCVI procedure? There is a diagram of implantation device to stimulate vagus nerve in RA patients in article. Suebee

[Suebee]

Also, I didn't see an explanation of why albuterol was administered in oral form as a copaxone add on. Based on these articles does it seem one could get the same result through inhalation vs oral? Could it be simply that it's easier to measure the dosage administered if in oral form? The science for this seems so promising, is there a way our group could push for more studies on the albuterol add on? My guess is there isn't enough data at this pt to get it prescribed off label.

[Suebee]

In my last post, I didn't intend to discourage. You've done great research, I hope your neuro can work with you on this approach. I appreciate you sharing the info too. I will discuss with mine.

[Cvfactor]

A different approach.

Hi Suebee,

Your question doesn't discourage me at all, I'm still going to pursue this with my neurologist. I think he will ultimately prescribe it off label as it has little risks associated with it and the trial data is compelling.

Copaxone Relapse = 0.37 relapses/year equates to 2.7 years until first relapse.

Copaxone + Albuterol = 0.09 relapses/year equates to 11.1 years to first relapse.

This is unheard of in any approved therapy for ms in terms of relapse rate. The study also looked at brain atrophy and there was a lower % atrophy in the Copaxone + Albuterl group but the number of patients evaluated did not provide enough power to conclude this to be statistically significant.

At any rate I think it would be worthwhile to pursue this in a phase 3 trial. The phase 2 trial was paid for by the National MS society and the primary endpoint measured was the Multiple Sclerosis Functional Composite (MSFC) which is a unknown measure in MS trials.

I suspect the MSFC was used because this was also developed by the National MS society. It's too bad because the real value of the trial is buried in the body.

Getting a phase 3 trial may be difficult since Albuterol is Generic but if there are suggestions please bring forward your ideas.