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Guest Jenny

Gene therapy & Isolation of Rosacea Genes

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Guest Jenny

Copied over from the old RRDi Forum Jan 2006 written by Brady Barrows:

Topic title: Suggestion by Geoffrey Nase, Ph.D.

Geoffrey Nase, Ph.D., made this suggestion for the RRDi:

"In all sincerity, you could change the face of rosacea by changing your foundation to just focusing of ssDNA therapy trials and isolation of rosacea genes. I can think of no better way to change the face of rosacea. These DNA labs are giving us FREE DNA for studies and independent publication. I am in no competition -- it would be great to have other foundations working on this.

My thoughts are ....... and these are just my thoughts. Narrow your focus considerably to one or two major focuses of your foundation. Then youve got something.

Gene therapy

Isolation of Rosacea Genes

Taking gene therapy from psoriasis (in human phase trials of cell adhesion molecules and inducible nitric oxide) and add rosacea to their list.

Focus young grasshopper and you might take the rosacea research world by storm. Sincerely.

Geoffrey

------------------------------------------------

Dr. Geoffrey Nase
Ph.D. Neuro-Vascular Physiologist
Rosacea Specialist and Consultant
http://www.drnase.com"

 

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Guest Jenny

For a long time now, I have held the belief that Rosacea is passed on gentically, a recessive gene. Recently, Joanne posted this in the Rosacea Forum and it made me think twice about Gene Therapy:

http://forum.rosaceagroup.org/viewtopic.ph...er=asc&start=15

Joanne: "I also take issue with the idea of gene therapy for rosacea"

Question: "Why?"

Reply by Joanne:

"Because I believe rosacea is not primarily a genetic disease. Yes, there is some correlation within families, but many things are inherited, both genetically and culturally. Our genes for fair skin, for example, and our eating habits are family traits. But it seems that rather than persisting at a low level in family lines throughout many generations, the incidence of rosacea has exploded in western societies in recent years. This says to me that environmental factors play a large role, and interact with genetic traits. I think what we tend to see as genetic predisposition is really traits selected for in the environments of our ancestors, which can be modified by new conditions, such as change in diet or exposure to enironmental pollutants.

We are still technologically a long way from being able to provide gene therapy for adults, but I'm sure that will come in time, probably sooner than we expect. But given today's genomic technology, a sufficiently large study would be able to dissect out some genetic predisposition correlations. True. But so what?

Say we pull out half a dozen genes that have alleles (natural variants) which have some small association with rosacea. Rosacea is clearly not due to less than a couple of genes, given the distribution in families. Suppose that together these half dozen alleles account for, say, half of the predisposition to rosacea, meaning that the unlucky person who has 'bad' alleles at all six of these genes has a 50% chance of developing rosacea. Given the change in rosacea incidence in recent years, I really doubt that we would be able to find any more association than this.

Now consider that every gene has multiple functions in our physiology and development. Every time we mess with one 'rosacea' gene, we are also affecting everything else that gene has a role in. A good example is the sickle cell anemia gene. The 'bad' allele that produces anemia when inherited from both mother and father, also protects against malaria, even in only one copy (from mother or father). So two 'bad' alleles = die from anemia, 2 'good' alleles = die from malaria. In parts of the world where malaria is endemic, this anemia allele is very important, so natural selection keeps it around. If we thought we were smart and got rid of the anemia allele by gene therapy, we would leave the patients exposed to malaria.

Similarly, it has recently been shown that the gene that is most commonly mutated in deaf people also happens to protect against infection and gives a higher pain tolerance. If we had decided to cure deafness by gene therapy, we would also be inadvertently messing with the patient's immune system. ALthough deafness is a trait that natural selection would usually weed out, alleles like this would be very important to a society challenged by a new epidemic, for example.

I think these sort of multifunctional alleles will prove to be the norm, rather than the exception, such that every time we tinker with a gene it will have multiple unexpected and unpredictable repercussions throughout our bodies. So for a disease in which we would need to modify multiple genes with who knows what side effects from each one, all in combination, while there is such a significant environmental component, it just doesn't make sense to me to focus on a genetic cure. Let's instead deal with the toxins we have imposed on ourselves. I think by trying for effective gene therapy we will be doing our health a disservice in many other ways, and potentially inflict much more harm than what rosacea itself presents us with, whereas if we go for the environmental factors we would be promoting better health in all aspects of our lives.

Again it seems like we are sitting back asking for a miracle cure, rather than dealing with what we can change for ourselves, right now."

Being that Geoffrey suggested that the RRDi focus on only two issues - "Gene Therapy" and "Isolation of Rosacea Genes", I was wondering if anyone else had some input on this.

Thanks

Jenny

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I think that the question you have to answer is, are you going to spread your potential research grants wide or focus on a few areas. In my opinion, the 2 areas are 1. understanding of genetic basis 2. understanding and adrressing the vascular issue. Understand 1. and im sure 2. will follow, but ultimately you have to decide whether the reseatch focus is on the 'hear and now' short term treatments or the long term cure which i belive genetic understanding will bring.

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I think that the question you have to answer is, are you going to spread your potential research grants wide or focus on a few areas. In my opinion, the 2 areas are 1. understanding of genetic basis 2. understanding and adrressing the vascular issue. Understand 1. and im sure 2. will follow, but ultimately you have to decide whether the reseatch focus is on the 'hear and now' short term treatments or the long term cure which i belive genetic understanding will bring.

I agree, I think genetic research has to be the priority. I would love to see the RRDi contribute something in this area.

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Agree this is likely to be genetic condition with many known environmental/dietary triggers(I favor something related to lipase, regardless of my unconfirmed idea).

I do not think it will be recessive gene or genes with 40% of rosaceans having family members involved, dominant with variable penetrance more likely. But, genetic is likely to be worth RRDi effort.

I do not have a favored (I do not work in genetics) researcher to suggest.

Supporting this (your interest and funding scientists already working on this) seem one good starting place.

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One recent example in which genes probably have a role, apologies for responding to myself!

Yamasaki K et al Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea.

Nat Med 2007 Aug: 13:975 suggests that overexpression of of one enzyme (kallikrein 5) which breaks apart cathelicidin may produce rosacea signs and symptoms.

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