Well, the time has come. I'm retiring from writing this blog.
It's a question of time. I don't have any. I work at a university, and in the start of fall term is hectic. Everyone wants to schedule their events from September to December. Courses are starting up. Important people are visiting.
And at the same time, I'm the father of two kids who are starting their own school years. There are the usual tensions with new teachers and fellow students, there's the endless making of school lunches, the PTA and Dad's Club meetings. Something I've realized: the power you have as a parent of a public-school kid depends on how much time you're putting into raising money for the school. If I find any free time, I need to be ready to put it into my kids and their school.
The lack of good subject matter is another issue. To write a blog you have to find a niche. My niche has been eczema research. It turns out that when you have a narrow niche it's often hard to find anything worth writing about. There appears to be a lot of research coming out, but in reality it is very rare to see anything that you could genuinely get excited about. Most research is published "salami-style," where the scientists report some tiny new finding that adds ever so slightly to the enormous pile of existing work. The ratio of valuable information to filler is very small. Sorting through the internet's fire hose takes time I don't have.
True, the academic term will eventually end, but I won't be returning. I don't want to blog in fits and starts.
You might, however see me writing occasionally on the National Eczema Association website.
I have enjoyed blogging. I've met some great people online and in person. I've learned loads about the medical condition I and my family live with. Not much has improved, but I feel like I now understand better what makes my skin the way it is.
For several months, I have been waiting for a cool new project to come out, one that I've been involved with in a small way. When it does appear, I'll add a post about it so it gets some publicity from being on top. You will like this new thing, I think.
Thanks for reading. Good luck keeping your skin healthy.
Tuesday, September 3, 2013
Thursday, August 1, 2013
Eczema, food allergies, and summer travel
Midsummer it's hard to find time to post. We're taking two weeklong family vacations not so far apart and with planning and packing and then getting swamped with work when you get back there's not much time to write.
Two aspects of traveling are relevant to this blog: how to take your eczema pharmacy along with you, and how to handle your kid's food allergies.
Last Saturday we got back from a trip to a family camp in the Sierra Nevada. It was awesome. I didn't think about work for a whole week and was so stress-free that I could jump in the pool whenever I felt like it and strut around in just my bathing suit. You've got to enjoy these times when you have them.
We ate in the camp mess hall. The staff were great about telling us what the ingredients were in all the food. Often they could give us a special dish without nuts or dairy, which are the two things my daughter's allergic to. But of course, she's a picky eater, and you can never tell what she's going to go for.
When we got back, I read about a tragic incident at a summer camp near Sacramento where a 13-year-old girl died after one bite of a Rice Krispies square containing peanuts. My daughter doesn't have an anaphylactic reaction to anything--not yet--but this was a sober reminder of how deadly nut allergies can be.
Our next trip starts on Wednesday when we fly to Nova Scotia for my parents' 50th wedding anniversary. We often go to NS in August and last year, coming back, we spent an extra day in Newark airport thanks to United Airlines, which we are NEVER FLYING AGAIN. I had run out of any moisturizer or steroid, which was my fault--but try finding fragrance-free moisturizer in the airport shops. Not going to happen. By the time we got home, my eczema was out of control and took several days to cool down to a point where I could appear in public.
Also, being out of food and having a kid with allergies in an airport was a different kind of nightmare. You can't find an ingredient list anywhere and everything seems to have nuts or dairy or whatever. My daughter was essentially reduced to eating potato chips for the better part of 24 hours, but we did gamble on getting her noodles from a random Asian restaurant. Just glad, now that I know she's allergic to sesame, that Asian restaurants in airports are far from authentic.
So this year? I'm going to bring too much moisturizer. And we're going to pack a day's worth of safe food for my daughter.
Hopefully we won't need it--we're flying Air Canada.
Two aspects of traveling are relevant to this blog: how to take your eczema pharmacy along with you, and how to handle your kid's food allergies.
Last Saturday we got back from a trip to a family camp in the Sierra Nevada. It was awesome. I didn't think about work for a whole week and was so stress-free that I could jump in the pool whenever I felt like it and strut around in just my bathing suit. You've got to enjoy these times when you have them.
We ate in the camp mess hall. The staff were great about telling us what the ingredients were in all the food. Often they could give us a special dish without nuts or dairy, which are the two things my daughter's allergic to. But of course, she's a picky eater, and you can never tell what she's going to go for.
When we got back, I read about a tragic incident at a summer camp near Sacramento where a 13-year-old girl died after one bite of a Rice Krispies square containing peanuts. My daughter doesn't have an anaphylactic reaction to anything--not yet--but this was a sober reminder of how deadly nut allergies can be.
Our next trip starts on Wednesday when we fly to Nova Scotia for my parents' 50th wedding anniversary. We often go to NS in August and last year, coming back, we spent an extra day in Newark airport thanks to United Airlines, which we are NEVER FLYING AGAIN. I had run out of any moisturizer or steroid, which was my fault--but try finding fragrance-free moisturizer in the airport shops. Not going to happen. By the time we got home, my eczema was out of control and took several days to cool down to a point where I could appear in public.
Also, being out of food and having a kid with allergies in an airport was a different kind of nightmare. You can't find an ingredient list anywhere and everything seems to have nuts or dairy or whatever. My daughter was essentially reduced to eating potato chips for the better part of 24 hours, but we did gamble on getting her noodles from a random Asian restaurant. Just glad, now that I know she's allergic to sesame, that Asian restaurants in airports are far from authentic.
So this year? I'm going to bring too much moisturizer. And we're going to pack a day's worth of safe food for my daughter.
Hopefully we won't need it--we're flying Air Canada.
Thursday, July 18, 2013
Eczema patients not protected by intradermal flu vaccine
When I talked to Donald Leung earlier this week (he's head of pediatric allergy & immunology at National Jewish Health, and leads the Atopic Dermatitis Research Network) he mentioned one interesting result that has already emerged from a small-scale ADRN trial. Leung and others showed that patients with atopic dermatitis were not adequately protected, by FDA standards, by the new influenza vaccine Fluzone.
Fluzone is administered using a super-short needle--the technique is called "intradermal" injection in which the vaccine gets squirted into the upper skin layers rather than muscle tissue.
Presumably the super-short needle is less scary than a regular needle, and more people will get their flu vaccinations this way; it could be a public health issue in the event of a flu pandemic.
Scientists know that the immune system functions differently in the skin of patients with eczema. Leung and colleagues looked at how 20 eczema patients fared with Fluzone, compared to 20 non-atopic patients. Twenty-eight days after vaccination, they measured the levels of flu antibodies in the patients' blood. The non-atopic patients met the FDA standard; the eczema patients did not.
The scientists published their results in a preliminary form as an abstract at the meeting earlier this year of the American Academy of Allergy, Asthma and Immunology.
Fluzone is administered using a super-short needle--the technique is called "intradermal" injection in which the vaccine gets squirted into the upper skin layers rather than muscle tissue.
Presumably the super-short needle is less scary than a regular needle, and more people will get their flu vaccinations this way; it could be a public health issue in the event of a flu pandemic.
Scientists know that the immune system functions differently in the skin of patients with eczema. Leung and colleagues looked at how 20 eczema patients fared with Fluzone, compared to 20 non-atopic patients. Twenty-eight days after vaccination, they measured the levels of flu antibodies in the patients' blood. The non-atopic patients met the FDA standard; the eczema patients did not.
The scientists published their results in a preliminary form as an abstract at the meeting earlier this year of the American Academy of Allergy, Asthma and Immunology.
Wednesday, July 17, 2013
New NEA post: Atopic Dermatitis Research Network needs trial participants
This week you'll find me blogging over at the National Eczema Association website. I interviewed Donald Leung of National Jewish Health about the Atopic Dermatitis Research Network. Three years in to a $42M program to investigate the links between genetics and our susceptibility to skin infections, the ADRN is registering patients with the NIH before proceeding with clinical trials.
They still need black and Hispanic patients to sign up--eczema, genetics, and skin pathogens are different for different ethnic groups. The better your demographic is represented in the trials, the more that scientists will learn that applies to you.
The ADRN has centers in Boston, Chicago, Denver, Los Angeles, Portland OR, and Rochester NY.
If you're interested in participating, email Judy Lairsmith at National Jewish or call 1-888-413-5852.
They still need black and Hispanic patients to sign up--eczema, genetics, and skin pathogens are different for different ethnic groups. The better your demographic is represented in the trials, the more that scientists will learn that applies to you.
The ADRN has centers in Boston, Chicago, Denver, Los Angeles, Portland OR, and Rochester NY.
If you're interested in participating, email Judy Lairsmith at National Jewish or call 1-888-413-5852.
Wednesday, July 10, 2013
Irwin McLean's filaggrin readthrough drug could be revolutionary
Recently I predicted that nothing resembling a cure for eczema would appear for at least 25 years. I followed that up with a prediction that if a surprise cure were to emerge, it would be an anti-itch therapy.
At least one reader disagreed, and pointed me to a strategy now being developed at the University of Dundee in Scotland: drugs to stimulate or enable filaggrin expression in patients with one or two defective copies of the corresponding gene, FLG. At least one such drug is in the very earliest stages of drug development, toxicology studies in animals. If the drug succeeds in human clinical trials, we might see it in clinics in about 15 years. Potentially, such a drug could help some of the patients most severely affected by eczema.
The best review on filaggrin I’ve seen was co-written by three authors, two of whose names I am familiar with as among the biggest in the field of eczema research: Irwin McLean, who led the team that linked mutations in FLG to increased risk of developing ichthyosis vulgaris and eczema, and Donald Leung, principal investigator of the Atopic Dermatitis Research Network. (The first author is Alan Irvine, a colleague of McLean’s who works in Ireland.)
FLG is a giant, and unusual, gene, one of the last to be sequenced by the Human Genome Project. It encodes an enormous protein, profilaggrin, which contains from 10 to 12 repeats that are cleaved off into individual filaggrin units. Filaggrin itself has several important roles in the upper layers of the skin: it flattens skin cells into their characteristic final shape; it helps bind these cells together into a barrier; and it breaks down into the acidic “natural moisturizing factor.”
Many mutations have been found in FLG. Interestingly, if you take any particular ethnic group (say Japanese), there will be a characteristic profile of mutations for this group that is likely to be different than the profile for another group (say Scottish).
All filaggrin variants are either “nonsense” or “frameshift” mutations in DNA that encodes protein (as opposed to so-called “junk DNA”). In a nonsense mutation, the correct DNA base has been replaced with a wrong one, and the upshot is that the protein-making machinery, known as the ribosome, runs into a code that it doesn’t recognize; it can’t add an amino acid to the growing protein, and it stops decoding profilaggrin at that point.
If the nonsense mutation occurs early enough, before the first filaggrin unit in FLG, no filaggrin gets made at all.
I believe that with a frameshift mutation (in which one or more DNA bases are missing or added) the protein is very likely to be terminated soon afterward. The end result is the same: little or no filaggrin.
In his 2006 Nature Genetics paper, McLean and his group identified two mutations, R501X (nonsense) and 2282del4 (frameshift), which have turned out to be the most common in Caucasian populations. Both R501X and 2282del4 occur early in the first filaggrin repeat. That means that if you have one such mutation, you will have one good copy of FLG and one bad copy; and if you have mutations on both your copies of FLG, you won’t have any filaggrin at all, and there is a high chance that you have eczema.
Soon after their 2006 discovery, McLean and first author Frances Smith applied for a US patent, “Prevention/treatment of ichthyosis vulgaris, atopy and other disorders.” The patent, number 8,338,386, was granted only recently, on December 25, 2012. It makes many claims, all relating to the ability of five antibiotic drugs, or potentially tRNA molecules, to force the ribosome to read through nonsense mutations.
McLean and Smith’s patent is aimed at the nonsense mutation R501X (they say so in the patent), because it occurs so early in the gene. Such a drug would also work for nonsense mutations later in the sequence.
The drug or agent would not work on frameshift mutations such as 2282del4, as I understand it.
One cool thing about a readthrough drug would be that it would have its strongest effect on people who had nonsense mutations on both copies of FLG. A readthrough drug would theoretically make both copies functional. People with only one mutated copy of FLG would still benefit from having that number increased to two.
In the patent,“atopy” is mentioned in the title and the background information, but neither “atopy” nor “atopic dermatitis” appear in any of the 14 explicit claims. I don’t know whether this matters. I'm not an IP lawyer. It seems curious that the inventors left it out though.
Another curious fact is that only five specific drugs are mentioned: gentamicin, paromomycin, neomycin, tobramycin and negamycin. There is no discussion of the drug discovery process—any tweaking of molecules for greater effect or less toxicity—that I can see. I don’t know whether this matters either.
From what I can tell, McLean’s group has at least one of these compounds, which has most likely been altered from its original structure, in “toxicology” (which means testing in mice, rats, etc.) (see page 16). If you look at this handy graphic provided by the FDA, you will see that toxicology studies are step 2 of 12 in the drug discovery-to-market process. So it is extremely early days and you have to keep in mind that, as I keep saying, almost all drug candidates fail at some stage of clinical testing.
A relevant factor is also that currently there is no FDA-approved drug that acts by this mechanism—by causing the ribosome to ignore nonsense mutations. Ataluren, a drug to cure Duchenne muscular dystrophy and cystic fibrosis, is a readthrough drug in phase III clinical trials. The FDA is apparently especially careful when approving drugs that are “first-in-class,” or the first of their general type. So it is worth following Ataluren’s progress closely; its success could mean that we might see an eczema readthrough drug sooner.
Hat tip to Anonymous (you know who you are)
At least one reader disagreed, and pointed me to a strategy now being developed at the University of Dundee in Scotland: drugs to stimulate or enable filaggrin expression in patients with one or two defective copies of the corresponding gene, FLG. At least one such drug is in the very earliest stages of drug development, toxicology studies in animals. If the drug succeeds in human clinical trials, we might see it in clinics in about 15 years. Potentially, such a drug could help some of the patients most severely affected by eczema.
The best review on filaggrin I’ve seen was co-written by three authors, two of whose names I am familiar with as among the biggest in the field of eczema research: Irwin McLean, who led the team that linked mutations in FLG to increased risk of developing ichthyosis vulgaris and eczema, and Donald Leung, principal investigator of the Atopic Dermatitis Research Network. (The first author is Alan Irvine, a colleague of McLean’s who works in Ireland.)
FLG is a giant, and unusual, gene, one of the last to be sequenced by the Human Genome Project. It encodes an enormous protein, profilaggrin, which contains from 10 to 12 repeats that are cleaved off into individual filaggrin units. Filaggrin itself has several important roles in the upper layers of the skin: it flattens skin cells into their characteristic final shape; it helps bind these cells together into a barrier; and it breaks down into the acidic “natural moisturizing factor.”
Many mutations have been found in FLG. Interestingly, if you take any particular ethnic group (say Japanese), there will be a characteristic profile of mutations for this group that is likely to be different than the profile for another group (say Scottish).
 |
| FLG (read from left to right; red hexagons are filaggrin units.) Common mutations in Asian and European populations. Look how early the nonsense mutation R501X appears. Figure 3A from Irvine, McLean, and Leung's NEJM review |
All filaggrin variants are either “nonsense” or “frameshift” mutations in DNA that encodes protein (as opposed to so-called “junk DNA”). In a nonsense mutation, the correct DNA base has been replaced with a wrong one, and the upshot is that the protein-making machinery, known as the ribosome, runs into a code that it doesn’t recognize; it can’t add an amino acid to the growing protein, and it stops decoding profilaggrin at that point.
If the nonsense mutation occurs early enough, before the first filaggrin unit in FLG, no filaggrin gets made at all.
I believe that with a frameshift mutation (in which one or more DNA bases are missing or added) the protein is very likely to be terminated soon afterward. The end result is the same: little or no filaggrin.
In his 2006 Nature Genetics paper, McLean and his group identified two mutations, R501X (nonsense) and 2282del4 (frameshift), which have turned out to be the most common in Caucasian populations. Both R501X and 2282del4 occur early in the first filaggrin repeat. That means that if you have one such mutation, you will have one good copy of FLG and one bad copy; and if you have mutations on both your copies of FLG, you won’t have any filaggrin at all, and there is a high chance that you have eczema.
Soon after their 2006 discovery, McLean and first author Frances Smith applied for a US patent, “Prevention/treatment of ichthyosis vulgaris, atopy and other disorders.” The patent, number 8,338,386, was granted only recently, on December 25, 2012. It makes many claims, all relating to the ability of five antibiotic drugs, or potentially tRNA molecules, to force the ribosome to read through nonsense mutations.
McLean and Smith’s patent is aimed at the nonsense mutation R501X (they say so in the patent), because it occurs so early in the gene. Such a drug would also work for nonsense mutations later in the sequence.
The drug or agent would not work on frameshift mutations such as 2282del4, as I understand it.
One cool thing about a readthrough drug would be that it would have its strongest effect on people who had nonsense mutations on both copies of FLG. A readthrough drug would theoretically make both copies functional. People with only one mutated copy of FLG would still benefit from having that number increased to two.
In the patent,“atopy” is mentioned in the title and the background information, but neither “atopy” nor “atopic dermatitis” appear in any of the 14 explicit claims. I don’t know whether this matters. I'm not an IP lawyer. It seems curious that the inventors left it out though.
Another curious fact is that only five specific drugs are mentioned: gentamicin, paromomycin, neomycin, tobramycin and negamycin. There is no discussion of the drug discovery process—any tweaking of molecules for greater effect or less toxicity—that I can see. I don’t know whether this matters either.
From what I can tell, McLean’s group has at least one of these compounds, which has most likely been altered from its original structure, in “toxicology” (which means testing in mice, rats, etc.) (see page 16). If you look at this handy graphic provided by the FDA, you will see that toxicology studies are step 2 of 12 in the drug discovery-to-market process. So it is extremely early days and you have to keep in mind that, as I keep saying, almost all drug candidates fail at some stage of clinical testing.
A relevant factor is also that currently there is no FDA-approved drug that acts by this mechanism—by causing the ribosome to ignore nonsense mutations. Ataluren, a drug to cure Duchenne muscular dystrophy and cystic fibrosis, is a readthrough drug in phase III clinical trials. The FDA is apparently especially careful when approving drugs that are “first-in-class,” or the first of their general type. So it is worth following Ataluren’s progress closely; its success could mean that we might see an eczema readthrough drug sooner.
Hat tip to Anonymous (you know who you are)
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