Will there ever be a cure for Down's syndrome?

Peter Elliott 
Copyright 2001 The Down's Syndrome Research Foundation Ltd

We are often asked if a cure will ever be found for Down's syndrome. That's a very good question and one we need to take a hard look at if we are to understand what medical research is helpful.

From the Oxford English Dictionary:
syndrome n. 1 a group of concurrent symptoms of a disease.
disease n. 1 an unhealthy condition of the body or the mind.

In 1866 Dr. John Langdon Down published a paper 'Observations of an ethnic classification of idiots'. Dr Down observed these particular patients had physical characteristics that made them look as if the were children of the same parents. About one third of his patients had these characteristics. It is this group of patients we refer to as having Down's syndrome.

Dr Down was deeply concerned about the welfare of those whose very humanity was denied by the majority. He expressed his disgust at contemporary practices in no uncertain terms, referring to one religious institution as 'a parody on philanthropic effort'.

Dr Down was far ahead of his time. In 1866 he had identified the genetic link to a disease process that would not be discovered for another 90 years. Were he alive today we can be fairly certain he would be conducting research to find a cure for the syndrome that carries his name.

In 1959 Professor Jerome Lejeune discovered the genetic cause of Down's syndrome was a chromosomal disruption known as a trisomy. (trisomy 21) Normally there are two sets of genes in each of 23 chromosomes in every cell in the body. One set is from the father and one set is from the mother. He discovered that patients with Down's syndrome had a third set of genes at chromosome 21. With the discovery that the cause of Down's syndrome is genetic in origin, there was a belief that a cure was now impossible. However Professor Lejeune was more optimistic and he believed a cure or more correctly a treatment therapy is possible. His focus was on targeting the metabolic consequences of having these extra genes. He believed that if we could understand the effect these extra genes had on the development and growth of the child and on their lives it should be possible to develop a treatment therapy. Some of the information that directs our research comes from the early work that he did. The Foundation Jerome Lejeune in Paris is providing part of the funding and is collaborating in our Antioxidant Research Project at the Institute of Child Health in London. They continue the work of Professor Lejeune in the search for a 'cure' which at this point is a search to find a treatment therapy that negates the effect of those extra (trisomy 21) genes. 

The Human Genome Project is now completed in its first draft. The justification for funding this massive project was to identify the genetic cause of all human illness and disease. About £210 million was committed by the Welcome Trust and there were many other funders. They hope to have the final finished 'gold standard' human genome sequence in 2003.Chromosome 21 has 225 genes. There are a total of (about) 30,000 genes in 23 chromosomes. There are two sets of 23 chromosomes so the contribution of these extra 300 genes (in trisomy 21) has to be weighed against the normal compliment of 60,000 genes. Patients with Down's syndrome really are a lot more normal than they are abnormal. The extra genes are also normal genes so there is a good opportunity to investigate those genes to discover what they do and how they might cause a problem when there is an extra set of these genes.

What is a Gene? A gene is the minimum amount of genetic information needed to make a protein which is a chemical important to life. There are thousands of those chemicals and they influence and control every aspect of our life. They control how we grow, including how that first fertilized cell divided and developed.  They systematically break down the genetic code that will decide what we look like, how healthy we are, or how prone to illness. They control how well our various vital organs are formed and they control how well they work. This includes the brain where chemical messengers connect the cells of the brain together and make it work. Every cell in the body has these genes and every cell's identity is mapped out by those genes that are turned on and those that are turned off. This makes each cell different in what it does and what it looks like. It also determines how they work.  

How about Stem Cell Research? A cell where the genes have not completely specialized is called a stem cell. These cells have the potential to create any one of many different specialized cells in the body such as brain cells.  Proximity to other cells seems to make the stem cells imitate the "program" of the cells nearby.   We all have these stem cells within the bone marrow and they are perfectly matched to our genetic code so there is no chance of rejection. Medical researchers are trying to use these cells to find a cure for certain disorders. One day it may be possible to cure mental disability with the introduction of the stem cells into critical areas of the brain where there is a need to replace damaged cells.  

Is Stem Cell Research Unethical?  Research that creates a new human life in order to harvest stem cells or vital organs including brain cells is unethical and it is immoral. Some will say that it is necessary to save human lives, but this is not true.  We already have stem cells in our body that are a perfect genetic match there is no need to resort to experiments where human life is created and then thrown away.  Some experimenters are now involved in cloning experiments so they can grow tissue that is a perfect genetic match.  They actually want create a new human life,  grow the organs they need then "harvest" those organs and discard the rest of the baby.  It has already been proposed to grow fetal brain cells in this way and use them to "cure" Alzheimer's patients.  All of this research is obviously unethical, it is immoral, and it is very dangerous because it cheapens all human life. Researchers have options that avoid these ethical issues and this includes the ability to make stem cells without involving the creation of a new human life. Growing new brain tissue from stem cells recently discovered in ordinary fatty tissue is one exciting possibility.  

How about a cure to turn off or remove the extra genes in trisomy 21? At the moment I don't know of any research that thinks this is feasible. Don't forget that the extra set of T21 genes is identical to the other two sets at genes at chromosome 21. So how do you turn off one set without effecting the others? Also genes in other chromosomes may be turned off by accident if we even attempted that kind of a cure. Then consider that there are billions of cells throughout the body and the brain. As these cells specialize they turn genes on and off to suit their needs. So its a very much bigger project to turn off these few extra genes and its a project no one has discussed so far. We need a safer and more practical alternative to this kind of 'cure'.

What research is feasible?  A good approach is to observe the patient and see what these extra genes are doing to the patient. Then try to negate any abnormal situation with a suitable treatment therapy. Our research is targeting this approach. We wanted to test Targeted Nutritional Interventions (TNI) to see if there was any proof that it worked. But first it was necessary to do a systematic review of research. The result of that review is on this website (Click here to see that paper).  From this review of research we discovered there was very convincing evidence that these patients had elevated oxidative stress. Almost double what is normal and this would certainly result in a situation that put their health at risk, it would also result in a higher incidence of illness and a slower recovery and there was a definite increased risk of brain damage. The logical treatment therapy is antioxidants but from our review zinc was also seen to be beneficial and folic acid and selenium were thought to be important. So a very big clinical research project was drawn up and that project is now underway at the Institute of Child Health in London. 200 babies will be in that study and it will last for 4 years. This is the biggest project in history for our children and every parent has a duty to provide some financial support. Click here to offer your support

An article in the New Scientist drew my attention to the role of zinc in Down's syndrome. We already have a very well prepared dissertation on this subject by Roxanne Eastland but now we had something new that finally looks like it might explain the link between 50% increased production of Super Oxide Dismutase (SOD) an antioxidant enzyme that converts free radicals into peroxides and this observation of increased in free-radical activity. The one should negate the other but this does not happen. Professor Ashley Bush believes that when there is a deficiency of zinc as there is in Down's syndrome much of the time, then the SOD which relies upon zinc for its formation becomes a pro-oxidant as it seeks out a source of zinc. So SOD which should be helpful is actually unhelpful and now we think we know why that might be. A big step forward for research but first we have to test that proposal and this requires another research project.

The outlook for a therapy that negates the influence of the extra genes in Down's syndrome is certainly moving ahead by leaps and bounds but it is held back for lack of funding and a shortage of researchers who can draw up a good research proposal. Even doctors will assume that the extra genes are mapping the child's life from the moment it is conceived. While some of the genes may map the outcome there is no common pathology for Down's syndrome, variation is the norm. Environment including the provision of a good healthy diet, loving parents and a stimulating existence results in a better outcome for every child and the same rule applies when the child has Down's syndrome. Down's syndrome is a collection of medical and developmental abnormalities easily catalogued, but not so easily understood. Perhaps too easily brushed aside by doctors with the comment "It's normal for Down's syndrome". But the sum total of these "abnormal" medical conditions is what define the syndrome,  the genes only predispose towards that abnormal risk situation,  at the moment there is no certainty that the genes positively map the outcome.  There is such variability in the outcome from one patient to another patient that there is a good opportunity to do more research in this area to find out why some patients do so much better (or worse) than other patients.  But the most obvious reason is that patients who do best will be getting better health care, better nutrition and a caring and stimulating life with lots of love and support from the family.  

SUMMARY:

Down's syndrome is a group of concurrent symptoms of a disease, and a disease is an unhealthy condition of the body or the mind.  The syndrome is caused by the additional genes in chromosome 21.  These extra genes interact with all of the other genes and with the environment. There  is no 'common' outcome and therefore there is no fixed pathology. More research is needed to find a suitable treatment therapy. Down's syndrome is not a fixed condition decided by the genes these children are born with. No more than your life was fixed in your genes when you were born. Our genes will predispose towards a growth and development outcome but environment and upbringing have a greater effect or at least an equal effect. Perfectly normal children who were mistreated in orphanages in Romania are an example of what happens when children are starved not only of food but also of love and affection.  Common sense and loving parental concern should guide us all as we try to do what is best for our children. There is good evidence that this results in the very best outcome for the child.  Negating the influence of those  (extra) trisomy 21 genes will help the child to develop more normally and have a longer and more healthy life. We need more and more parents to believe in a better future for their children. It is our HOPE for a better future that gives us the enthusiasm, the willpower and the energy to make that future happen.   Hope is very important because it leads to ACTION and this results in progress.

Towards a cure. Thanks to the vision of just a few parents the DSRF has made some good progress in the past 6 years towards a cure for Down's syndrome. If all we do is change a few attitudes we achieve that objective. But we have done even more with the discovery of the need for antioxidants and the need for zinc. Now we have to produce the medical evidence from research projects. Those projects are very expensive and no-one wants to pay for them. Parents need not be afraid to get involved in pushing for medical research all the best medical research projects are driven by parental concern.  

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