2nd licensed Gene Therapy drug approved

The 2nd GENE THERAPY drug to be approved by the EU authorities has hit the market in Europe.
The first gene therapy drug, Glybera, was approved by the EU in 2014.
The new drug, Strimvelis, is for 'bubble boy disorder'.
Gene Therapy will likely be a cure for genetic systemic malodor disorders.

Gene Therapy is of interest to those with metabolic genetic malodor disorders because gene therapies will likely be 'cures' for genetic disorders. So if someone has a sub-par FMO3 enzyme that causes systemic body odor and/or halitosis, gene therapy could be considered the 'holy grail' cure.

Gene therapy has been suggested for about 30 years but a main obstacle was that it often involves viruses and these could cause a severe/fatal immune reaction. Also there may be some resistance from big pharmas as a one-treatment cure may mean loss of revenue. And investment costs and cost of treatment were seen as too costly (Glybera cost around $1.2 million per treatment.

But finally the obstacles seem to be clearing, and the technology has caught up.

FMO3 protein
Oxidizes/reduces many sulfides and  amine (and phosphates)
Gene produces a 532 amino acid code (and a stop at 533)

How would gene therapy be relevant to metabolic/systemic body odor/halitosis ?
My view is that most causes of systemic B.O/halitosis are probably to do with a sub-par FMO3 enzyme issue. In these cases gene therapy should make the FMO3 enzyme work normally. Gene therapy has taken 30 years to get to this stage but over the next 10 years could quickly become cures for genetic disorders.

How do Gene Therapies work ?
My impression is that they are usually manufactured viruses that are put in the target gene to make the gene work correctly. It will probably be to do with what type of fault you have in the gene. For FMO3, Most people have 'missense' faults, where an incorrect amino acid has been put in the 532 amino acid sequence. So this would probably require a 'missense' drug. Another severe type is a 'nonsense' fault, where the 532 long FMO3 code is told incorrectly to stop early on (a false stop). One drug, Ataluren, is being targeted to ignore this 'false stop' so in the case of FMO3 the 532 code will ignore the false stop. But 'nonsense' mutations are much rarer than missense and I presume a nonsense targetting drug would not help with a missense mutation.

Links to story on Strimvelis drug approval :
BBC news site
News18.com

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By sysbodyodor

fecal body odor, gene therapy, genetics, metabolic malodor, research

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new Chinese paper : FMO3 gene therapy in mouse

Chinese academic research
FMO3 mutation successfully replaced by a normal copy in a single cell mouse embryo
They think it will 'cure' the mouse and each future generation
This is stage 1 (proof of concept), so probably would take years to reach a clinical therapy if that were possible
Probably the 1st time this has been tried with FMO3
A commenter tells me this is unlikely to lead to a therapy for anyone other than embryos

Link (pubmed abstract) : FMO3 gene therapy in single cell mouse embryo : China

comment :
A group of Chinese academics seem to have for some reason tried to change a mutated FMO3 gene in a mouse embryo and change it to a 'correct' FMO3 gene using gene therapy. It seems they were successful. Why they chose FMO3 is not known.

Keep expectations in context :
While it's exciting to see the concept of gene therapy for FMO3 in a mammal proven, an expert has suggested to me it is not  likely to result in a therapy for humans other than those at the embryo stage.

Still, it's an interesting development. It would be interesting know why they chose FMO3 as the gene to try, and if they plan to continue this research using FMO3.

Why FMO3 is of interest to systemic body odor :
It is my belief that FMO3 gene is responsible for what is commonly referred to as 'Fecal Body Odor', which I think is due to the build up of FMO3 substrates. FMO3 oxidizes many sulfides and amines.

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By sysbodyodor

fmo3, FMO3 research, gene therapy, important, metabolic malodor, possible future therapy, systemic body odor, systemic malodor syndrome

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Crispr gene editing therapy for genetic faults

About : CRISPR gene editing therapy. A new method of altering DNA code to 'repair' faults in the code. The first study has been proven to repair a fault in mice. Presumably has a way to go to be used on humans.

I don't know much about it, but CRISPR seems to be a potential method for 'gene therapy' / 'enzyme replacement therapy'. The hypothesis seems to have been known for a few decades, but it seems it has only been shown to work on mice recently, to treat the genetic disorder tyrosinemia. Presumably it has a long way to go until it is might be available as a therapy for humans. It seems to be basically a 'gene editing tool' that can correct errors in the genetic code. It seems to have evolved from a way bacteria protect themselves from viruses.

The good thing about 'gene therapy' methods is that presumably they may be adapted to repair any/most enzyme faults in humans. In the case of what is known as 'fecal body odor' (in practice may be 'sulfides and amines of a certain structure malodor'), my own current opinion is that FMO3 enzyme may be the enzyme most likely 'at fault' for the majority of 'fecal body odor' cases, so any 'gene therapy' would be targeted at FMO3 (if I was correct). 

So CRISPR news is something to look out for.

Incidentally, tyrosinemia is a terrible disease that ruins a person's liver in particular, due to an inability to break down tyrosine. Tyrosine is supposed to give off a cabbage smell. Anyone with 'severe' genetic tyrosinemia (type 1 ... i.e. due to severe enzyme deficiency) will have serious health problems, however I do wonder if 'carriers' may be prone to bursts of the cabbage smell. One difference from this and my suggestion of 'FMO3 malodor' is that tyrosinemia would be a specific smell that never changes, whereas most on the forums report of a wide range of 'fecal/gas/malodorous smells', which to me suggests an enzyme that deals with a wide range of compounds, whereas the tyrosine altering enzyme will probably just deal with tyrosine.

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links :
MIT news
PHG Foundation
Youtube search : crispr
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By sysbodyodor

gene therapy, possible future therapy

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