Cure genetic diseases?

I’ve mentioned this before, but I have muscular dystrophy and I’ve been waiting patiently for, oh, 20 years now for a cure. But a thought occurred to me a while ago and I was wondering if any medical or scientific types can help me puzzle this out:

How can a genetic “disease” be “cured”? Since it’s written into my genetic code and is a part of me, then isn’t it a bit like trying to “cure” my brown hair or green eyes?

I guess this is a pretty dumb question; obviously, scientists haven’t come up with a cure yet, so I assume they don’t know either. But they’ve been working on it for a while now, what do they hope to do? Do they think they will someday be able “rewrite” the genes of people who are already affected? Can anyone help me understand this?

Thanks :slight_smile:

This kinda interests me as a laymen.
I’ve noticed there has been quite a bit of experimentation going on in “curing” diseases that are due to the lack of a particular substance or protein being manufactured, like diabetese.
Most of these seem to involve getting a retrovirus to insert DNA into part of the body to make up for the lost function.
The problem seems to be control, however.

The standard way of attempting to cure these genetic diseases is to work out which genes are defective and which proteins they are failing to produce, and then inserting genetic material coding for those proteins into your body. In the case of muscular dystrophy it is some of the muscle proteins that are not being correctly coded for. If it were possible to insert a healthy gene for those muscle proteins into your body (presumably your muscle cells) then the correct protein would be produced and hopefully your muscles cells would be fully functional with normal lifespan. Your body would go on producing the defective protein, but hopefully this would be overridden by the functional one that is now being produced.
Similarly it is at least theoretically possible to ‘cure’ your green eyes or brown hair. Both are caused by a partial de-pigmetation of the associated areas. This de-pigmentaition is presumably caused because the genes that code for melanin are ‘defective’ in these areas. All we have to do is figure out what those genes are, and insert some ‘functional’ genes and hey presto your hair will turn black and your eyes brown. The proteins responsible for the green and brown pigmnents will still be there,they’ll just be swamped by the functional proteins now being produced.
Curing someone of brown eyes and black hair would presumably be much harder (read impossible with current technology) because that would require removing all the functional genes and replacing them with ‘defective’ ones. Fortunately with genetic diseases the genes involved usually seem to be defective, and the proteins they produce able to be masked by functional proteins when available.

Thanks, Gaspode, for explaining it to me in a way I can understand. It is my understanding that the missing protein for my kind of MD has been identified; do you know what kind of progress is being made in figuring out how to insert those functioning proteins? (And, while they’re at it, can they insert some of Cindy Crawford’s proteins?–not the mole one, though.)

Muscular dystrophy is a disorder caused by a mutation in the dystrophin gene (as you are aware). This gene links the muscle filaments (which do the pulling) to the muscle membrane (which links the muscle eventually to the bone). Dystrophin basically transduces the force. In MD, a faulty dystrophin is unable to transduce the force of muscle contraction.

The answer is obvious. As Gaspode said, replace the faulty gene. This is called “gene therapy.” There are a number of problems with this, however.

First, you have to clone a correct copy of the gene. This is already done. The problem is that dystrophin is a massive gene, so you need to find which part in a given individual is broken and construct your gene therapy around the individual’s mutation. This is a lot harder.

Next, you have to get the correct gene into the correct cell. Even a bigger problem. Most vector systems (the systems used to transport the gene) are based on viruses. You have to basically construct a virus to infect muscle. You need to strip this virus down so it is non-immunogenic. You need to suppress cell mediated immunity. You need to have a good delivery system for both the virus and for the DNA into the cell.

Third, you have to ensure a replacement. This is a huge problem. Out of 3,000,000 base pairs of genome, you need to find your appropriate gene site and replace all or part of the faulty gene. Not only do you have to inject the DNA into the cell (usually with a virus), but you have to hope that some of it gets to the nucleus. Muscle cells are quite large and form syncytiums with their nuclei peripherally. It makes a hard target to hit.

Fourth, you are now replacing a mutant protein (and one with which you are born) with a foreign protein. There can be all types of immunologic issues with this.

Gene therapy is in trials for several diseases right now. Some of these are cystic fibrosis, citrullemia, and several other single gene disorders. It is very hard. Most of the problems so far center around the virus vector (gutted adenovirus) that they are using. It is somewhat immunogenic, and actually caused a fatal cardiomyopathy in a clinical trial last year. That, and so far most have been unable to ensure a complete replacement.

This is a definite region into which medicine is heading. We are not there now. We probably won’t be there for at least a decade. It is incredibly difficult because it acts as a nexus to so many systems – immunology, molecular and human genetics, virology, biochemistry, cell biology, and pathology. We make progress every year, but this is not something in which there will be a big breakthrough anytime soon, unfortunately.

Keep well.

Sorry Gr8Kat, I forgot to submit my reply and you replied in the interim.

A few points (for your information).

First, the most comprehensive scientific summary of most genetic disorders can be found an Online Mendelian Inheritance in Man (OMIM). Here is the entry on FSHMD.

The FSHMD gene has not been cloned yet. It has been mapped to the q end of chromosome 4, with some implications of a deletion causing a defect in gene expression somewhere not in the deletion. The picture is not straightforward, however. There may be a mouse model, however, which would speed research into the disease immensely.

Gene therapy for muscular dystrophy is an active area. A few months ago, a report was made in the Proceedings of the National Academy of Sciences of the USA ( in which they claim to have ameliorated muscular dytrophy in a mouse model using an adeno-associated virus vector. Here is the article :

Anyway, I hope this helps.

Note: I am a PhD student working on viable methods of disease control by genetic modification
Quite frankly, even if all the problems outlined above are solved, gene therapy for someone who has suffered from a chronic genetic illness for decades is a practical impossibility for most of these diseases. If it is simply the lack of a crucial enzyme or hormone (i.e. diabetes etc…) it may be possible to stimulate cells in the body to produce it. But for something like MD, where damage has occured over a long time, recovery would probably be impossible. The idea is to identify affected individuals at birth (or before) and apply the genetic treatment then, before a lifetime of damage has accumulated. For someone already affected, the best option would probably be to cure them so that their offspring would be disease-free, even if they still suffered.