Gene Therapy Cures "Bubble Boy"

bofh31337 writes "NewScientist is reporting that Welsh boy Rhys Evans has been cured of the fatal severe combined immunodeficiency ("bubble boy") disease. The medical team, lead by Adrian Thrasher, was able to take the stem cells that give rise to immune cells from his bone marrow and add a normal copy of the gene to the stem cell using a retro virus. Seven months after treatment, Rhys was cured."

The Article...

[Anonymous Coward]

Gene therapy has cured Welsh baby Rhys Evans of the fatal "bubble boy" disease. "His progress seems nothing short of a miracle," says his mother Marie. Another boy treated more recently continues to improve. The treatment, carried out at London's Great Ormond Street Hospital, is one of only a handful of successful gene therapy trials in people. It is also only the third trial of gene therapy for severe combined immunodeficiency or SCID. Alain Fischer's team at the Necker Hospital in Paris reported the first-ever treatment in 2000, of two boys, while an Italian-Israeli team recently reported promising initial results with two people who have another form of the disease. Nine people in total have had gene therapy at the Necker Hospital, and seven of them are doing well. But the researchers at Great Ormond Street think they have developed a better way of delivering the gene to correct the fault that causes the disease. Solitary confinement The type of SCID that the Welsh baby had is "X-linked", caused by a fault in a gene on the X chromosome that makes an immune protein called interleukin-2. The disease affects boys because they only have one X chromosome. The faulty gene stops the development of T cells, a key part of the immune system. Children must be kept in isolation to protect them from catching infections and usually die young. A bone marrow transplant can cure the disease, but suitable donors are only found in a third of cases. To treat the boys, the Great Ormond Street team took the stem cells that give rise to immune cells from the two boys' bone marrow. Then they used a modified form of a retrovirus found in gibbons to add a normal copy of the faulty gene to the stem cells. The virus has altered spikes on its surface which may mean it binds better to stem cells and transfers the gene to them more efficiently, team leader Adrian Thrasher told New Scientist. The engineered stem cells were then returned to the boys' bodies. Rhys Evans is now back at home, with normal T cell levels, seven months after treatment. The second child, treated just three months ago, continues to improve at home. The Great Ormond Street researchers say they are planning to treat another four boys over the next two years.

More coverage...

[abhinavnath]

The Guardian [guardian.co.uk], and Yahoo [yahoo.com]

Re:Question

[glwtta]

The laws don't restrict the research itself, they restict the number of cell lines available for research. So yeah, it would've been possible in the US, provided the scientists could get their hands on the stem cells.

my experience

[azosx]

I wrote a paper this last semester in college on embryonic stem cell research. The possibilities in this field of research are endless. It's certainly not suprising to me this discovory occured in Europe. It's unfortunate the position the United States has taken towards stem cell research. It's pretty much closed to door and made the possibility of discoveries such as this very unlikely here in the U.S.

www.nih.gov/news/stemcell/index.htm has the latest information about what's taking place in the U.S. in regards to stem cell research. It's a great resource for anyone wanting to learn more about this amazing new science.

Re:Question

[ageitgey]

The US has laws limiting embryonic stem cell research. They don't care if use use cells from yourself (as they did with the 'bubble boy'). The issue is whether or not more break-throughs of this type could be made faster by using stem cells from all the frozen embroyos laying around (which are basically big clumps of stem cell :)

gene therapy

[borg]

The biggest problem with gene therapy is that long term expression of the target gene has been difficult to achieve. The inserted sequence, depending on the gene carrier, may or may not be inserted in to host genome. Actual insertion into the host genome is undesirable because of possible malignant transformation (insertion of the target sequence disrupts the function of a tumor supressor protein, or turns on a pro-tumor protein, etc.). Existing as a genetic sequence outside of the genome proper has also failed to achieve more than temporary expression of the desired protein.

This article describes a technique to increase the effiency of the transfer of a therapeutic gene sequence into a target cell. It does nothing to address the biggest stumbling block of gene therapy. While this is sexycool news, being cured for 3 or 7 months doesn't mean being cured for life.

Claimer: IAAMD
I don't mean to be a downer. We're just a loooong way off from real gene therapy.

Yes, Maybe

[Shook]

A stem cell is cell that can turn into different type of cells. There are many type of stem cells, and the controversy in the US is only over human embryonic stem cells. These cells can only be obtained by destroying what many consider a human life.

Stem cells in adult bone marrow can turn into many types of blood cells. From the article, it sounds like the stem cells used came from the patients' own bone marrow so human embryos probably weren't used. The article doesn't say where the normal copy of the gene came from, but I doubt it would need to come from a human embryo.

Re:Are we good at this, or what?

[big_groo]

The problem with a retro-virus, is that each time it replicates, it takes a small chunk of the host's dna with it. Each iteration of the virus is a different virus altogether. Hence, the problems with developing a vaccine or cure. Influenza and HIV are both retroviruses. Google knows. Look up 'retro-virus/immunology' if you're interested in more reading...

-1 offtopic.

retrovirus information

[jest3r]

A retrovirus is special because it contains an enzyme called reverse transcriptase. This enzyme works backwards, translating RNA [accessexcellence.org] into DNA. Retroviruses contain RNA within their protein coat, and use reverse transcriptase to create DNA that can be inserted into the cell it is attacking. One of the most famous (or perhaps infamous) retroviruses is the HIV retrovirus, which causes AIDS.

Retroviruses are being investigated for 3 reasons:

1) They can be used as vectors to transport genetic information into a host cell.

2) Reverse transcriptase can be used to isolate DNA sequences from a mRNA chain so that the gene can be manipulated through bioengineering techniques.

3) To find a way to genetically engineer a cure for AIDS. If the action of reverse transcriptase can be halted somehow, the HIV virus will have no way to spread its harm through the body and millions of lives could be saved.

more info [thinkquest.org]

Re:Question

[nathanm]

The laws don't restrict the research itself, they restict the number of cell lines available for research.

They don't actually restrict the number of stem cell lines, they merely limit government funding to the existing lines. Anyone could start new lines with private funding.

Also, the policy only refers to embryonic stem cells. The bubble boys were cured with their own stem cells.

Re:How do Retro Viruses work?

[Digitalia]

Retroviruses are cute little viruses that write DNA from RNA using reverse transcriptase, an enzyme. These viruses possess the ability to write that DNA into pre-existing DNA and, in this manner, convert cells and such to their cause. HIV is a retrovirus. However, much more beneficial retroviruses exist. The ability to write DNA into cells allows these viruses to be used to modify live cells. Take this with a grain of salt: I've never been a very good Bio student.

A great example of "safe" genetic engineering

[encebollado]

This gives a great example of the safer of the two types of gene engineering, somatic. This type of gene therapy only modifies the genetic makeup of certain cells in the body. None of the effects of the changes could propogate onto his children. I wish we could see more of this type of gene therapy.
The other type, germline, alters genes in gametes (eggs and sperm). Any changes here would probably (at least with our technology) be irrevsible and would be carried by any decendents. Thankfully, people are being more cautious with this kind since the effects would be much more permanent and far reaching.

Re:How do Retro Viruses work?

[doricee]

In all cells things go like this:
DNA -> RNA -> Protien
aka the central dogma of biology

A virus is incapable of doing this by itself, hence it cant reproduce by itself.
So it hijacks the host cell.

There are several classes of virus, based on
what it injects into the host cell. Some have subclasses that are based mostly on what it looks like (capsid and envelope) of the virus.

I. dsDNA
(papovirus) warts
(adenovirus) respiratory disease
(herpesvirus) herpes, chickenpox
(poxvirus) smallpox, cowpox

II. ssDNA (parvovirus)
roseola

III. dsRNA (reovirus)
diarrhea viruses

IV. ssRNA that can serve as mRNA
(picornavirus) polio, common cold
(togavirus) rubella, yellow fever

V. ssRNA that is a template for mRNA
(rhabdovirus) rabies
(paramyxovirus) measles, mumps
(orthomyxovirus) Influenza viruses

VI. ssRNA that is a template for DNA synthesis
(retrovirus) HIV, tumor viruses

The Retroviruses work something like this:
RNA -> DNA -> RNA -> Protien

This is a case where biology doesnt follow the central dogma of biology! The other virus classes still follow the central dogma.

Another interesting disease agent is a prion, but thats involves a lot of speculation.

-hope that helps.

Re:X chromosomes

[jso888]

I should hope not.

People normally have 23 pairs of chromosomes. Of those chromosomes, only 1 is an X chromosome, and one a Y chromosome in boys. Girls have 2 X chromosomes.

The other 22 pairs of chromosomes may be X-shaped, but they most assuredly not what biologists refer to as X chromosomes; they're referred to by pair number 1 through 22.

Furthermore, having an abnormal number of chromosomes (aneuploidy) can cause congenital disease. In the case of sex chromosomes, I refer you to Klinefelter's and Turner's syndrome. In the case of other chromosomes, Down's syndrome (extra copy of chromosome 21), trisomy 13 and 18 (extra copies of chromosome 13 or 18).

Sheesh.

Re:X chromosomes

[PlatinumMac]

No, everyone has 44 autosomal chromosomes and 2 sex chromosomes (either one X and one Y or two Xs).

X chromosomes are distinctly different from the autosomal chromosomes. No human being can live with a missing autosomal chromosome (e.g. only one chromosome 21 instead of two) -- embryos with this type of defect are miscarried so early that they are not even detected, even though embryos with three copies of an autosomal chromosome (a defect arising from the same mistake in meiosis which causes the loss of an autosomal chromosome in some embryos) are detected -- some even live to adulthood (Down syndrome). On the other hand, all human beings can be said (in general) to have only one X chromosome; in females, one X chromosome is almost completely inactivated in each cell.

Re:Question

[WowTIP]

Anyone could start new lines with private funding.

Afaik that is not true. Bush banned the development of new embryonic stem cells ~6 months ago. The congress is even discussing a ban on importing embryonic stem cells.

Sure, they could always try to get new lines from adult stem cells, but those attemps has so far not been very successful.

The retrovirus is harmless.

[red_gnom]

The retrovirus is used only as a harmless vehicle for transportation of the good gene. It has an ability to penetrate into cells. Eventually the virus gets destroyed, and the "fixed" gene remains inside.
Gene therapy [escience.ws]

Similar method was originally tried on cystic fibrosis patients, but the positive results lasted only for about three weeks, after that repaired cells were replaced back again with the faulty ones.
It seams to be more complicated.
Cystic Fibrosis Gene Therapy [uq.edu.au]

Re:More coverage...

[red_gnom]

And also:

Gene therapy [escience.ws]

Cystic Fibrosis Gene Therapy [uq.edu.au]

Re:Really?

[dondelelcaro]

What the fuck is a retro virus?

A retrovirus is a virus that carries its genetic material in RNA instead of DNA, and as such, needs RT, or reverse transcriptase, in order to make DNA from its RNA. The other major type of viruses are DNA viruses, which do not require RT to integrate into the host's genome.

Other issues

[nucal]

A few reasons why this worked so well:

• This form of SCID is due to a total gene deletion - so that gene replacement was feasible. A lot of genetic diseases are due to genes expressing proteins that are mutated, but still produced. These mutant proteins can frequently have a dominant negative effect, that is, they mess up normal copies of the protein or other proteins in the cell. In this case, adding more good copies of the gene in question will not help.
• Being able to treat stem cells in isolation is a big advantage, since you don't have to target cells in the context of the whole body (needle in haystack problem). In culture, the virus to cell ratio can be really high, increasing the probability of successful infection. Also, stem cells successfully expressing the gene of interest can be selected and preferentially propagated in culture before re-introducing into the patient.
• Another big advantage in being able to treat isolated cells is that you avoid the potential problem of an immune response to the virus itself. This was a big problem [wired.com] recently with a different class of viruses. In some ways SCID, being an immune deficiency, is the ideal disease for viral gene therapy, since these patients are less likely to react to the virus itself.

Re:How about AIDS?

[Steve B]

Nope -- see the Straight Dope [straightdope.com] column answering that question.