Gene Therapy

[Mowgli]

One of the most amazing animals in the world (in my eyes) is the salamander; this animal (an amphibian) has the ability to grow whole limbs if they are severed...within a matter of weeks, this animal regenerates all that is necessary for a new limb (muscles, bone, cartilage, blood vessels).

 

We as humans also have this capability, but on the journey from foetus to child this ability gradually fades, but it is not lost completely for example, the human liver, if damaged has the ability to re-grow to its original size and shape.

 

 

Modern medicine is now just beginning to understand and discover the genes that make human parts grow. This means that the human body can be able to re-grow missing or damaged parts without the need for operations or mechanical devices. A field in which this new technology is being researched is in the treatment of heart diseases. Scientists have discovered a gene, that when inserted into the body can promote the production of blood vessels (angiogenesis), further research is being carried out to understand what exactly switches growth on and off. By the simple insertion of this gene into the heart, it could mean that the patient could re-grow new blood vessels to replace their old ones and save their damaged heart, replacing conventional therapy.

 

Cardiovascular Disease (CVD) includes "dysfunctional conditions of the heart, arteries, and veins that supply oxygen to vital lifesustaining areas of the body like the brain, the heart itself, and other vital organs." If oxygen does not arrive to the tissue/organ, it will cause part or all of that tissue/organ to die. It is thought that 1/3 of us will die from heart diseases, in the US CVD accounts for 42% of all deaths.

 

What if people with heart ailments could stop taking daily medications because their own bodies made the medicine they needed?

 

That’s the idea behind gene therapy: introducing genetic material into certain cells and "reprogramming" them to produce proteins that can treat or correct problems.

 

I could go on and on nomads, but I'd like to know your opinions on this subject

 

Salaams

 

ps I just focused on CVD because it is of a particular interest

[Cara.]

Interesting topic, Idil. Just a couple of questions. I'm not in genetics so please bear with me if the answers are obvious.

 

1. What is the delivery method? I mean how to get the modified gene into the cell? I recall attenuated viruses were the most promises vectors way back when I first heard about gene therapy. Is that still the case?

 

2. Is there possible risks from cancer? eg, from the modified tissue perhaps getting out of hand, and in particular your example of blood tissues like vessels and the heart. Anginogenesis is a typical early step in tumor formation/growth.

 

Thanks.

[Mowgli]

Using harmless viruses is still the prefered method of getting the genes into the body

 

Risks of cancer as far as I can remember was only found in the X linked Severe Combined Immunodeficiency (SCID)...the trial was done in france (if memory severs me right) on 11 patients and 2 of those patients ended up developing leukemia...inshaAllah I;ll get back to you on the details for that as I have to rush to a class...

 

but in CVD, a gene promoting Vascular Endothelial Growth Factor (VEGF) was found to trigger angiogenesis and it was inserted into patients via a simple injection in the heart. Before one clinical trial was stopped in 2000, Dr Isner and co found that in 70% of the patients in clinical trial found that angina problems were greatly decreased, however 2 people in the trial died (cause of death was said to be not related to the gene therapy, but not proven)...like I said, i'll elaborate more...gotta rush to class

 

Salaams

[Castro]

^ Isn't this haraam?

[Caano Geel]

Callypso-I-like-it-so (just in case you know the song!)

 

most this is still blue skies research, and cannot yet be fully applied. We know these genes do something but we dont understand exactly how they do it. So for example most of gene theraphy i've read of the gene modification is applied to the embryo i.e a lab rat with the particular gene is engineered. As far as delivery methods go, this is crude to say the least. but its hoped that technologies such as nano-technology i.e. minirobots or specificaly eng. pathogens will deliver the theropy.

 

As far as cancers go, who knows?! we are only begining to understand the micro-scale behaviour of the genes, their macro-scale behaviour, especially when you consider the cummulative effect of many genes interacting is too complex to analyse as yet. The field is still to young to consider as something that is truely reliable or viable, but it does offer many many exciting possibilities

 

idil, thanks for the post, tell us more --

 

Castro, yes its all xaram which is why you are not allowed to do it .

 

cheers

[Shirwac]

Too much science fiction, let things be how they were made!!!

[Mowgli]

Salaams

 

Castro good question...I don't know about the Islamic point of view in gene therapy, but I could tell you about some of the ethical issues surrounding it, in the above example I gave for the treatment of cardiovascular disease, it is a type of gene therapy that can not be passed on the individuals offspring...gene therapy can be divided into somatic gene therapy (involves all cells except sex cells) and germline (sex cells) gene therapy

 

Germline gene therapy is the most controversial topic (which is also what i have the most issues with). Even though it could stop future generations in a family from having a particular genetic disorder, it is still uncharted territory as the effects on the development of a foetus are still unknown and neither are the long term side effects.

 

This also raises another point, because people who would be affected by germline gene therapy are yet unborn, they cannot not choose for themselves whether or not to have the treatment.

 

Success is built on the rubbles of failure and this is true for medicine, we have learnt from a process of trial and error. Take for example the history of transplant (although not ethically right) there were stories of doctors who used to have bets with each other...they'd take a leg from a white dog swap it for the leg of a black dog...or they'd get the heart and place it in the neck (obviously before the discovery of rejection).

 

I mean do you guys agree that doctors have the moral obligation to patients and future generations to treat disease?

 

Shirwac...I'd like to point out what genetic engineering has already contributed to our society, e.g. the treatment of infertility, synthetic insulin etc. It is one thing to say let us leave things the way they were...but imagine you have a relative/friend, very close to you who is suffering from angina...they cannot walk 100 feet or shave without feeling excruciating pain. What would you do if a doctor told you only they needed to do was a non invasive technique and within a matter of days they'd feel a thousand times better?

 

Caano geel...nanotechnology now we talking! Give it 15 years and everyone will know what molecular nanotechnology is! When it comes to cancer, I am much more interested in potential vaccines, but we can leave that for another topic.

[Caano Geel]

Idil, i agree with you on the contraversy of germline therepy, but do you not think its just an extention of our social make up. And infact a potential socail equaliser.

 

Let me put it another, we already socially select based a particular socially defined fitness. You know your child can pottentially have a better life if you have cold hard cash behind you, therefore given the choice of a rich or poor partner, most people will go with the rich. This is in affect social selection. people going with the certainty over doubt.

 

As a species we have aleady transcended the 'biological' as the prominant factor that determins our path in favour of the social. So while blind animals may die of because they are not able to hunt, humans can rely on the extended social infrastructure to look after -hence survive and pass on thier genes.

 

This has two effects, first the mean fitness of out genetic pool is reduced since we homogenise our populations - i.e. diseases that would of wiped out the succeptibe dont anymore, so their defects can be passed on through the generations. Second, we are absolutely reliant on the our extended social structure to maintain us. .. giving a prophetic meaning the ohrase 'no man is an island'.

 

anyhow coming back to my point, isnt germline therepy just another natural by-product of us having more control over our environment.

[Mowgli]

Salaams

 

I got carried away in replying to your post, but for some strange reason when I clicked to submit, there was an error and my page closed

 

But to summarise on what I wanted to say...I agree with you the sense that gene therapy is an extension of our social make, but I do not agree with you when you say it can be a social equaliser…

 

I think that clincal benefits must outweigh the risks of those to the individual patients (which is not being done enough)...efficacy and toxicity of the therapies are not being reported properly…gene therapy is still a novel and experimental technique and is only being used in extremely rare cases...in the near future, it is most likely to become more mainstream and therein lies the problem. It will become a very very expensive therapy for the normal jamac, farah, and cambaro to afford. Should gene therapy be given to those that can afford it (ie the rich)? Is this morally right? No it isn’t. Eventually, I believe that humans will abuse this technology, all of us will not be able to afford it…such advances in technology could only lead to oppression and genetic “apartheid†and make society less accepting of those that are different. Plus you forget that what is desirable in one culture is not in another.

 

 

Common sense tells us that it might be better to try to prevent misfortune rather than have to deal with its consequences. Unfortunately, in the realm of health it isn’t as simple matter. The majority of cardiovascular diseases are preventable simply by a change of diet, losing weight and exercise. In 2001 (figure from Komaromy), only 4% of the money in the healthcare system in the UK was spent on prevention and primary care, whereas 55% was spent on the treatment of disease. Although treatments continue to be developed and improved, the proportion of people dying remains high, therefore it seems logical that preventing heart disease should be the number one priority.

 

Do you guys think, given the choice that doctors should shift emphasis away from those who are already sick in order to preserve the health of those in the future?

[Cara.]

Caano Geel,

 

Idil, i agree with you on the contraversy of germline therepy, but do you not think its just an extention of our social make up. And infact a potential socail equaliser.

Nah. It will do the opposite. Cold hard cash --> ability to "buy" the right genes for ones offspring (depending, of course, on how much genes actually control phenotype!). I somehow can't see insurance companies covering this sort of procedure, even if it will reduce their costs later (perhaps people would even be less likely to purchase insurance).

 

Idil,

 

The French study you quoted sounds intriguing, I'd love to hear more when you have time.

 

Castro,

 

I think just about anything (including eating pork) is Halal to preserve life. And like Idil said, one may have moral misgivings about a procedure right up until their life or that of their loved ones' is at risk. Then all bets are off...

[Cara.]

Idil,

 

Do you guys think, given the choice that doctors should shift emphasis away from those who are already sick in order to preserve the health of those in the future?

I think it goes against the Hippocratic oath or something. It's one thing to practice triage, to judge between 2 ill patients and treat the one at greater risk, but it's another thing entirely to refuse treatment for an ill individual so as to preserve resources for the healthy. In some cases, a doctor might decide that 1 patient is beyond help, and treat another that has a better chance of survival, but most chronic diseases are treatable. The mortality rate from CVD has actually been decreasing due to the plethora of treatments available (what's increasing is the prevalance and incidence rate).

 

I hope that made sense...

[Mowgli]

Sorry Cally, I can't seem to find the article, but I can tell you a lil bit more about it...SCID is genetic disease which is found only in boys (aka baby in a bubble syndrome). It's a disease where the kids are born without a functioning immune system, meaning they have to live in a completely sterile environment (most children do not reach adulthood). the only possible cure they have is a bone marrow donor or gene therapy. It said that the reason why the two boys developed leukemia was because the gene therapy activated a oncogene LMO2, there was also a third case in which a boy died from the leukemia (there were four oncogenes activated including LMO2).

 

You are right about the Hippocratic oath, but money spent on disease prevention within the healthcare system is most likely to divert funds from treatment services.

 

salaams

[BonaFied_CriTic]

Cool, so if i ever lose a toe i did be able to grow it back, lol shidy are my pretty toes...anywayz i hardly doubt one can grow back an organ they lost. If we are ever meant to regenerate like salamanders, then i did think we would have discovered this trait a long time ago. Besides things are easier said then done. I feel sorry for the people they are going to experiment with. Someone is sure gonna miss few toes and thumbalina(aheem aheem wordette) would miss her thumb.

[Snake-i]

Right off the top of my head idil, there are a couple of problems with limb regeneration...and also with the blood vessel regeneration you mentioned.

 

Cells can be manipulated to produce other things, but there have been problems. An early trial was to create cells that would produce insulin, which would then be injected into the pancreas of insulin deficient diabetics. They worked, and would happily produce insulin all day long...which became the problem. The production of insulin is a complex feedback mechanism that responds to the amount of food taken in, the amount of energy expended, and a few other conditions. The level of insulin produced by a healthy pancreas varies over the day, and by dietary need. These manufactured cells just put out the same amount of insulin, no matter what.

 

With something complex like a fully functioning limb, another challenge not yet met by scientists is differentiation. There are cells for bone, muscle, blood vessels, nerves, skin, and they must all "build" the right amount, for the right amount of time. Without a mechanism to make sure that bone cells produce more bone cells, or muscles cells more muscle cells, problems are created.

 

Then of course, thee is the "shut off" mechanism, which scientists have not yet found. Like the insulin cells, what would happen if the cells making the new arm or leg just kept on making the cells which they were programmed to do? You might ned up with an arm that was 6' long--wonderful if you wanted to play in the NBA, but a real bear when you went to look for a suit...

 

Finally, there is the matter of appropriate function. Cells injected into the heart to create new blood vessels are a woderful idea...but we can't control whether they will make the blood vessels, and whether the vessels will connect to the parts of the heart that have been damaged.

 

The Human Genome Project is working to overcome these difficulties, and perhaps in 30 years or so, may have over come some of them...but right now, they're still in the dark.

[Mowgli]

Despotic...our bodies already regenerate to a certain extent, but its gradually lost the older we get (Hayflick limit). Growing a whole toe is a tricky process, but we already regenerate to a certain extent e.g skin cells last a lil over 2 weeks and our stomach lining is replaced constantly, bones heal themselves...our bodies are yet unable to deal with the same amount of truama that a salamdar does...but small scale stuff, we can handle

 

Regeneration has been studied for centries, but it has only been since the last that we are now able to see what's going on at a molecular level.

 

Wisdom...I think stem cell therapy has a lot of potential, the potential to change the face of human diseases as we know it today...but alas the one thing holding it back is as well as the lack of funding is the avaliability of stem cells...futher research needs to be carried out before the questions you posed can be answered.

 

Injecting the VEGF into patients heart, so far has caused no problems such as the complications you mentioned...also you forget that ppl who recieve gene therapy are ppl who have failed all other conventional treatments; (one of the men in doctor Isner's study was told by his previous doctor "to sit still until technology catches up with you")...they'd suffer angina attacks from simple things e.g shaving, walking etc. Even a little increase in blood flow in previously ischaemic areas goes a long way. For example, even patients with kidney failure need just 10% of their cells functioning again and they'd be able to go off dialysis. Leukemia patients are injected with erythropoietin (hormone) which accelerates the body's production of red blood cells, although it is not a cure, it goes a long way in the management of the disease. However, more clinical trials and research needs to be done, to assess any long term complications.