Hacker News new | past | comments | ask | show | jobs | submit login
Scientists discover asthma's potential root cause and a novel treatment (cardiff.ac.uk)
106 points by tchalla on April 24, 2015 | hide | past | favorite | 25 comments



Link to the paper, "Calcium-sensing receptor antagonists abrogate airway hyperresponsiveness and inflammation in allergic asthma": http://stm.sciencemag.org/content/7/284/284ra60

Abstract:

Airway hyperresponsiveness and inflammation are fundamental hallmarks of allergic asthma that are accompanied by increases in certain polycations, such as eosinophil cationic protein. Levels of these cations in body fluids correlate with asthma severity. We show that polycations and elevated extracellular calcium activate the human recombinant and native calcium-sensing receptor (CaSR), leading to intracellular calcium mobilization, cyclic adenosine monophosphate breakdown, and p38 mitogen-activated protein kinase phosphorylation in airway smooth muscle (ASM) cells. These effects can be prevented by CaSR antagonists, termed calcilytics. Moreover, asthmatic patients and allergen-sensitized mice expressed more CaSR in ASMs than did their healthy counterparts. Indeed, polycations induced hyperreactivity in mouse bronchi, and this effect was prevented by calcilytics and absent in mice with CaSR ablation from ASM. Calcilytics also reduced airway hyperresponsiveness and inflammation in allergen-sensitized mice in vivo. These data show that a functional CaSR is up-regulated in asthmatic ASM and targeted by locally produced polycations to induce hyperresponsiveness and inflammation. Thus, calcilytics may represent effective asthma therapeutics.


Tl;Dr - calcium receptors in the lungs are linked to allergic asthma - and a class of drugs developed for osteoporosis appears effective in preventing the allergic reaction from being triggered. (Edit : in in vitro tests, and models)

Which given the shit I have poured into my lungs for twenty years is probably a nice thing to hear.

What is not a nice thing to hear is how a small but plucky university (ranked fifth in UK) is struggling so much for cash they have to put out press releases mentioning lack of funding - twice. That's not something I notice when MIT announces a breakthrough. We could double our science budget (5bn) and not really notice it among the debt repayments and welfare bills and wasted infrastructure projects.


Cured mine. I've told this before, but I take Magnesium (250mg) and Iodine (1-2mg) every day. This has "cured" my asthma. I put that in quotes because as someone pointed out there is no recognized cure, and I have not stopped, so I don't know if the condition would return. But it beats the heck out of inhaled steroids. Going on 1 year with no meds and no problems - PFT says lungs function above average. Of course YMMV, but why not try it?


You could just grew out of it. I had asthma since 3 years old, till around 19 I had attacks very often, and a few times each year I had to be hospitalized. Since then it become much less of a problem, and I had not needed to be in hospital for 10 years already. No change in meds (except since few years I only get them when I have attack and it's very rare - a dozen times a year maybe).

I've heard it's often the case for others (but you still need to have spirometria every few years to check nothing's going wrong).

On the other hand I got colitis ulcerosa at around that time when asthma stopped being a problem..


Because maybe you're personally just lucky and not having any symptoms for whatever reason? And because "just try it" can do real harm?

My anecdote for you: both of those are in the prenatal vitamins I take and have been taking for a while.... along with singulair, dulera, and my rescue inhaler. No positive change here.


Because my PFT showed the lungs of an 84 year old (twice my age) prior to treatment. Then after giving up treatment for self treatment for a while I had it done again and have lung function above average. Also, my decision was not on a whim, it was based on research. And finally, your prenatal vitamins do not contain much iodine - it should be milligrams, not micrograms (yep, I know about how much you're getting).

In this case, just try it should not do any harm. 250mg of magnesium is not a big deal. My doctor said iodine can screw up your thyroid - that's an old medical myth, but I've had mine checked a few times and the levels are very much in range.

So I stand by "just try it" along with YMMV because not everyones condition is the same.


That "old medical myth" has studies as recent as 2011/2012 showing that consumption of over 400 micrograms/daily of Iodine can cause subclinical hypothroidism [1]. That study needs to be confirmed, but given current recommended consumption in the 150-300 micrograms/daily range, recommending the consumption of 4x recommended levels or more as "should not do any harm" is strictly bad advice.

I'm stoked for you that you seem to have managed to treat your asthma problems with two mineral supplements, but please try to cite your research before trying to give medical advice.

[1] http://ajcn.nutrition.org/content/early/2011/12/26/ajcn.111....


This is news about a preliminary animal model and in vitro tissue study, not news about a clinical trial with human patients. From the Cardiff University press release (not usually a good source for a medical story):

"The team used mouse models of asthma and human airway tissue from asthmatic and non-asthmatic people to reach their findings."

"If we can prove that calcilytics are safe when administered directly to the lung in people, then in five years we could be in a position to treat patients and potentially stop asthma from happening in the first place," added Professor Riccardi." Do I need to add emphasis to the words "if" and "safe" and "could be" and "potentially" here, or is that already apparent to everyone?

I care about finding effective asthma prevention and treatment, as I have close relatives who have asthma, but this isn't the news I have been waiting for, not yet. It will be wonderful if other researchers are able to replicate these preliminary findings and if findings about this receptor in human tissues helps lead to development of an effective asthma treatment, but that is not a sure outcome from this news, alas.


It sounds like they want to give everyone that thinks they could get asthma this drug on a regular basis, and then claim the non-asthmatics as successes.


Do calcilytics increase or decrease calcium in the patient? http://www.wikinvest.com/stock/NPS_Pharmaceuticals_%28NPSP%2... says:

"Calcilytics are small, orally active molecules licensed to GlaxoSmithKline (GSK) for development and eventual sale. They act on calcium receptors to cause brief increases in plasma levels of parathyroid hormone in order to stimulate the growth of bone, which might be beneficial in the treatment of osteoporosis. "


>They act on calcium receptors to cause brief increases in plasma levels of parathyroid hormone in order to stimulate the growth of bone, which might be beneficial in the treatment of osteoporosis.

From what i read here http://en.wikipedia.org/wiki/Parathyroid_hormone the release of PTH causes release of calcium from bones into blood, it also causes increased absorption of calcium from intestine. So one can see how osteoporosis situation may become better or worse depending on a lot of other factors.

Anyway googling "asthma and calcium" brings articles as old as '83, so there seems to be long established connection as Ca ions regulate muscle contractions.


Great, I wonder if this is also cause of related Cron's disease and Colitis ulcerosa.


"a class of drugs developed for osteoporosis appears effective in preventing the allergic reaction from being triggered."

... am I the only one who thought "surely someone taking this drug for osteoporosis also has asthma? See if it's helped."


The fact that the active ingredient in a drug may help to cure or remediate multiple conditions doesn't mean the medicine you take for one will have any effect on other conditions even if the drug is effective against them.

Drugs are very specific and dosage and application (delivery mechanism) are quite important. For example clioquinol a drug used to treat fungal infections most commonly "Athlete's Foot" has now been proven to be very effective at slowing down and even reversing the neural degeneration in Alzheimer patients to a point in which persistent treatment might prevent the onset of dementia altogether.

And as you might guess it wasn't discovered when some one had both a fungal infection and Alzheimer and got "cured" simply because the topical application of clioquinol does absolutely squat in a case of Alzheimer and for the "drug" to become Alzheimer medicine an application method which allows it to breach the blood brain barrier is required, as well as a completely different dosage than one would find in a topical cream.


The nebulization of the drug is a significantly different way to administer it compared to its previous administration.


FTA, the drug wasn't any good at treating osteoporosis, although it wasn't otherwise harmful


You develop asthma as a child. Old people have osteoperosis. It sounds like this drug is meant to prevent it developing so the patient populations don't really fit


I beg to differ; you don't have to be old to get osteoporosis. Likewise, you can develop asthma at a later age. IANAMD but I work at a medical centre, deal directly with patients and medical staff and have come across a few such instances.


From the abstract: Thus, calcilytics may represent effective asthma therapeutics

That's the real story.

Keep in mind this mechanism is for allergic asthma, that's about ~1/2 (?) of all asthma patients?


No, non-allergic (intrinsic) Asthma is a fancy name for a "panic attack" besides that the other causes of non-allergic asthma are commonly various infections, in any case non-allergic is not a chronic condition.

Chronic Asthma or "Allergic" Asthma an auto immune disease in which the immune system triggers a violent response which causes the airways to pretty much close up, which is the actual Asthma you hear about when people say "I got Asthma".

While the symptoms of both Asthmas are quiet similar, the treatment is very different. Yes if you go to the hospital due to a very bad panic attack or have a bad respiratory infection they might put you on a vapaorator which is also used to treat actual severe Asthma attacks but besides that there's nothing much in common in form of treatment, nor should there be because the causes of that Asthma are either psychological or environmental which are quite easy to fix.


There's another cause of asthma, apart from allergic and intrinsic, I know, because a lot of my early asthma attacks were caused by it.

I had acid reflux, which was tracked down as one of the causes - once I started taking a drug (Prepulsid/Cisapride) to strengthen the muscles by the stomach, a lot of my attacks subsided.

I still suffer from allergies, and get the occasional attack, so it wasn't the only cause.

Professor Casimir in Belgium is probably the reason I'm still alive - and has done a lot of amazing research into Asthma and Allergies. Need to look him up and see if he's still practising actually.


A detailed criticsm/explanation of this is here:

"Not OP's fault, but the headline and the story itself are extremely inaccurate. This post should be labelled "misleading."

The story's deck says: "Scientists at Cardiff University and Kings College London have found out what causes asthma and how to switch it off "

This is not true. The researchers found a pathway that can trigger some parts of asthma, but the researchers do not claim that this is the cause of asthma. Most asthma researchers now believe that the disease has probably many different causes, all leading to a similar set of symptoms.

In the story itself, the reporter writes "...researchers at Cardiff University and Kings College London identified which cells cause the airways to narrow when triggered by irritants like pollution."

This as well is not true. The researchers looked at airway smooth muscle cells, but it was already known that these cells are responsible for the constriction seen in asthma. What this team did discover is a type of receptor in these cells that can trigger this constriction.

"Crucially, drugs already exist which can deactivate the cells. They are known as calcilytics and are used to treat people with osteoporosis. "

These aren't drugs, because none of them have been approved by any government agency. And they definitely haven't been prescribed by any doctor to treat osteoporosis. In fact, many have been abandoned as possible treatments for osteoporosis. Also they don't deactivate the smooth muscle cells. They deactivate the receptors in those cells.

Finally, the claim that asthma could be cured in five years is extremely problematic. First, even if these molecules get approved as asthma drugs, they would not cure the disease. People would still have asthma. They'd just have a new medication they'd take to prevent symptoms such as wheezing and breathing problems. And, going back to what I wrote above, this is probably not going to treat all asthmatics because there isn't a singular root cause of the disease.

And the biggest issue here, and what the story leaves out, is that study, in part, involved studies of a mouse model of allergic asthma--one type of the disease. Mouse models are great for pointing in a direction, but they are not people. And for asthma, mouse models don't have the greatest success rate in finding drug leads. So until there are clinical data on these compounds, it is way too early to call these treatments for asthma. And definitely not cures.

Again, this isn't OP's fault, but this story is extremely misleading. "

http://www.reddit.com/r/science/comments/33kucg/asthma_drug_...


This article is weak. Here is more information: http://www.cardiff.ac.uk/news/view/96649-researchers-hugely-...


Thanks. I would request the mods to edit the link submitted.





Guidelines | FAQ | Lists | API | Security | Legal | Apply to YC | Contact

Search: