Occasionally scientific medicine takes a leap forward by discovering a new technology to address an entire category of disease. The development of antibiotics to treat and vaccines to prevent infectious diseases is probably the most stunning historical example. Prior to antibiotics the treatment for infectious diseases was supportive, or simply ineffective. Now they can still be very serious, but most are treatable and even curable.

One category of disease for which there is still no cure is genetic diseases. Most genetic diseases can be treated only with supportive care. Some can be significantly mitigated – for example phenylketonuria is a genetic disease resulting in the inability to metabolize phenylalanine, resulting in the buildup of toxins that damage the brain. Brain damage can be avoided, however, by screening at birth and then a very low phenylalanine diet for those affected. The progress of some genetic diseases can be slowed by treatment, and for many others only symptomatic treatment is available. There is no treatment, for example, that significantly alters the course of any muscular dystrophy.

Genetic counseling is available, once a history of genetic disease is known, and this may allow the prevention of passing on genes for severe genetic illnesses. Essentially you can choose not to have children to avoid passing on a bad gene.

I wrote yesterday about the possibility of genetic sorting – using techniques to ensure that the good copy of a gene, and not the disease copy, is passed onto offspring. If perfected this is likely to be the most efficient and effective way to treat genetic diseases – by preventing them. The day is probably not too far off when it will be feasible and cost effective for every person to have a complete genome sequencing as a routine health maintenance procedure. There will be copious advantages of this to the individual, but also this will allow very effective genetic counseling – before the appearance of any genetic disease.

A couple could have their genomes compared to see if they share any genes for a recessive genetic disease (ones that require two copies of the disease gene in order to manifest the disease). If they have no bad recessive genes in common, they can comfortably undergo “unguided” conception. If, however, they share bad recessive genes one or the other (probably the sperm, as this will be easier) can be sorted to prevent a double genetic dose going to any offspring.

The same can be true for dominant genetic diseases, where only one copy of the disease gene is necessary for the disease to manifest. Typically, an affected potential parent would have one disease gene copy (called an allele) and one normal allele. This would normally carry a 50% chance of passing on the disease to any children – but why take a chance when you can ensure that the good allele gets passed on.

Until the day comes when we can simply prevent all genetic diseases, we are left with the challenge of treating those who are already affected. Treating the effects of the bad genes varies in effectiveness to almost complete in a few diseases, to minimal in most. The holy grail of treating genetic disorders is gene replacement therapy. This involves using one or more techniques to actually swap out the disease gene for a normal version. If successful, such therapy can accurately be called a cure. (Although, unless the gene was also swapped out in the gametes, the genetic disease could still be passed onto offspring.)

This technology has proven very challenging. One approach is to design a retrovirus with a normal copy of a gene then infect the patient with the virus which will then insert the good gene in the patient’s cells. This works for diseases where the bad copy of the gene is not producing a toxin or doing something bad, it just doesn’t work so the body is missing a protein the gene would normally make. Therefore, you could insert a replacement gene any old place in the genome, without removing the bad copy, and this will enable cells to make some of the missing protein and significantly reduce or eliminate the negative effects of the disease.

The problem is that the engineered retroviruses have a nasty habit of causing infections, in one trial resulting in the death of a a patient. But the technology is not dead, the theory is sound and researchers are diligently working on the technical hurdles. By the way – this is one reason why I am very cautious about predicting new technology. It is easy to get excited about a theoretical new treatment, and many enthusiasts will argue that the theory is valid and there are no reasons the technology will not work. But often the real limitation in a new technology is not the theory, but the practice. There are often technological difficulties that may or may not be overcome. There are also economic concerns – overcoming the technical problems may be possible but just not cost effective. And in medicine there is the problem of risks and the unintended consequences of interfering with a complex biological system.

Therefore, until I see good studies done in actual people, I am very cautious about any claims. Success in basic science and even animal research is no guarantee that a treatment will work in people. Actually, only a small minority of pre-clinical (pre-human) research ultimately translates into successful medical treatments. So always be wary of clinical claims based upon pre-clinical data.

This caution should also apply to this new study of gene therapy in mice. John H. Wolfe, V.M.D., Ph.D., a neurology researcher at The Children’s Hospital of Philadelphia, and his team have successfully used a neutralized virus called adeno-associated virus (AAV) as a delivery mechanism. The purpose of the study was to see if by injecting the virus into a part of the mouse brain that is highly connected to other parts of the brain, would that successfully spread the gene around the brain. The results were very positive.

This is very exciting. It demonstrated the utility of the neutralized AAV as a vector for gene therapy. It also shows that a limited exposure to one part of the brain will spread the desire gene throughout the brain. This strategy may limit the risk of a disseminated brain infection from such treatments. They also found that cells that took up the gene started producing the desired enzyme and even spread it to neighboring cells. So not every since cell would need to take up the new gene for the treatment to work.

I have been following the saga of gene therapy since entering medical school, so any advance like this is very exciting to me – doubly so since this is applying gene therapy directly to my field of neurology. But still – I am cautious from years of having premature enthusiasm disappointed. This is a mouse study. It will be years before we see this applied to humans in trials, and more years before people are actually getting treatment – if all goes well.

But medical research is all about hope for the future, so I will remain cautiously hopeful.