Hidden Miracle of all Downs Syndrome Children

Hidden Scientific Miracle of All Downs Syndrome Children

Dr. Judah Folkman came to the Harvard Medical School’s Massachusetts Eye and Ear Infirmary to give a talk on his research which involved his quest to find the secret reason of why Down’s Syndrome patients rarely get solid tumors. He came to MEEI to give an incredible grand rounds talk and asked if anyone has ever seen a Down’s Syndrome person with Proliferative Diabetic Retinopathy. This was in 2005. No one in the esteemed audience had ever heard of such a patient.

There was a race around the world to find such a person as they held the secret to how it is that Downs syndrome peoples rarely get cancers. Yes, they can get leukemia, but they rarely get other solid tumors. This incredible medical fact about these patients occurs because they have an extra copy of Chromosome 21. And somewhere on that gene, no one knew at the time where, was a gene that protected them from angiogenesis, the creation of new blood vessels. Dr. Folkman is considered the Father of Angiogenesis in his findings that tumors need new blood vessels to grow. If you stop angiogenesis, you stop cancer growth and many other disease that bring devastation with new blood vessel production, such as diabetic retinopathy and wet macular degeneration.  

Dr. Folkman became my advisor and in one of our meetings in 2005 I asked him why it was so hard to find the patient he came searching for at MEEI. He leaned over and said, “It is a a tragedy that all these Downs Syndrome babies are being aborted by their mothers.” I was shocked at the truth of his words. It was a tragedy. Clearly it was a tragedy from a spiritual level, but if moms knew the amazing secret these babies held, even from a purely secular view, they might give these babies a chance at life. 
Many do not know that Dr. Folkman was the son of an incredible Rabbi. Dr. Folkman was an incredible person who taught thousands unforgettable lessons about medicine, science, and life. 
I have come to know many families with childrens with Downs Syndome. Many are able to have very productive lives and work for a living. Many can drive. Many have graduated high school and college. It is a blessing to be able to see and work with these little angels. It is amazing that because of these little angels, in part, we have come closer to finding the genes that cause angiogenesis and tumor growth and we are even closer to finding a cure for cancer. 
See this article in Nature published in 2009 with more information. 
Sandra Lora Cremers, MD, FACS


Why people with Down’s syndrome get fewer cancers

Extra gene cuts growth of blood vessels that feed tumours.
Boy with Down's syndromePeople with Down’s syndrome have extra genes that slow tumour growth.Punchstock
A gene on the extra chromosome that causes Down’s syndrome helps to protect those with the disorder from some types of cancer.
Sandra Ryeom, a vascular biologist at Children’s Hospital Boston in Massachusetts, and her colleagues experimented with mice and with human cells to show that an additional third copy of theDSCR1 gene (also known asRCAN1) can suppress the growth of the blood vessels that feed cancerous tumours1.
“This is a big finding,” says Ryeom. “It offers us all these new targets for cancer therapy.”
An extra copy of chromosome 21 causes the developmental disabilities associated with Down’s syndrome. But some of the extra genes are also thought to explain the lower prevalence of some cancers in people with Down’s syndrome. A 2002 study of almost 18,000 people with Down’s syndrome showed their mortality from cancer was less than one tenth that of the general population2.
A study published today in Nature1, provides an explanation for the trend. It suggests that the extra expression of the DSCR1 gene suppresses pathways that some cancers use to signal angiogenesis — the growth of the blood vessels that cancer tumours need to thrive.

Starving cancers

The researchers tested the regulatory effects of Dscr1 in mice by injecting lung and skin cancer cells into normal mice and into Ts65Dn mice — mouse models for Down’s syndrome. Rather than the normal two copies of each gene, the Ts65Dn mice have three copies of 104 of the 231 genes on the human chromosome 21, including DSCR1.
The researchers showed the mouse models of Down’s syndrome had around 50% less tumour growth than normal mice after 3-4 weeks. The researchers next isolated the effect of Dscr1 by testing mice that had three copies of Dscr1 but normal numbers of the other chromosome 21 genes. These mice also had about 50% less tumour growth after 3 weeks, suggesting that Dscr1 could be largely responsible for tumour suppression.

“Clearly, there is more than one factor at work.”

To see whether other extra genes on chromosome 21 were also involved in tumour suppression, the researchers took away the extra Dscr1 gene but left the Ts65Dn mice with three copies of the other chromosome 21 genes. These mice had about 25% less tumour growth than normal mice after the same period of time — suggesting that the Dscr1 gene is important but doesn’t explain all the tumour suppression observed in Ts65Dn mice.
“Clearly, there is more than one factor at work,” says Ryeom. “We think that four or five genes may be acting together to suppress angiogenesis and tumour growth.” So the researchers went looking for other genes that might also reduce cancer growth in people with Down’s syndrome. Follow-up experiments using mouse cells grown in a dish showed that the extra expression of Dscr1 in combination with another chromosome 21 gene, Dyrk1a, suppresses angiogenesis and tumour growth further.

Human effect

To see what happens in human Down’s syndrome, the team used induced pluripotent stem (iPS) cells derived from skin cells from a healthy individual, or from the skin cells of an individual with Down’s syndrome.

“It’s remarkable that we can do research on Down’s syndrome that can tell us something about how to treat cancer.”

When iPS cells are injected into immuno-suppressed mice, they grow teratomas — tumours consisting of a variety of types of cells. When normal stem cells were used, the tumours grew blood vessels. But in the Down’s syndrome teratomas, the blood vessels budded but never fully formed, because angiogenesis was supressed.
It’s a rough approximation of how the genes could work in humans, but “anything that shows work in mice is relevant to humans is important”, says Charles Epstein, a geneticist at the University of California, San Francisco.
“It’s remarkable that we can do research on Down’s syndrome that can tell us something about how to treat cancer,” says Kairbaan Hodivala-Dilke, head of the Angiogenesis Laboratory at Queen Mary, University of London.
But she suggests another mouse model called Tc1 is a better proxy for Down’s syndrome because it has three copies of around 95% of the human chromosome 21’s genes.

Preventative pill?

Hodivala-Dilke also questions whether the pathway that DSCR1 affects in the cells that line blood vessels can be targeted for drug development.
“[The pathway] exists in a lot of different types of cells,” she says. The worry is that if new therapies tamper with a pathway that is not specific to the blood-vessel lining, it could have broader implications than just the suppression of angiogenesis.
Although her team haven’t done all of the controls, Ryeom thinks a particular type of the protein produced by the DSCR1 gene is “fairly specific” to the cells that line blood vessels.
Ryeom’s team is already trying to isolate the best targets on the regulation pathways for drug development. She says that since only one extra gene is required to greatly reduce angiogenesis, one day when therapies are available, they could be more like taking “a preventative vitamin, rather than a toxic drug”. 
  • References

    1. Baek, K.-H. et al. Nature advance online publication doi:10.1038/nature08062 (2009).
    2. Yang, Q., Rasmussen, S. A. & Friedman, J. M. Lancet 359, 1019–1025 (2002). | Article | PubMed | ISI |
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