News & Views Archives

Issue No. 1, Fall 2004

Welcome to our first quarterly newsletter! We are very excited that this project is finally getting off the ground. This will be the space where we will keep you posted on everything that is happening at the Center for Research and Treatment of Down Syndrome and in the Down syndrome community. Among many things, we will feature research and treatment progress from the Center and elsewhere.

So what’s been happening at the Center lately? The biggest news it that we have finally managed to launch our completely overhauled website. We hope that you like what we have done. This project has been very important to us, because it is the best means by which we can keep the community informed about what we are doing.

We are pleased to announce that our Center is expanding: Seven new research teams have joined us! Please welcome Drs. Wyss-Coray, Tsien, Crabtree, Smith, Huang, Yang, and Madison. 

In the spotlight

Neurobiologist Ahmad Salehi, M.D., Ph.D.
By Sietske Heyn, Ph.D.

Ahmad Salehi obtained his M.D. at the Medical University in Tehran, Iran and his Ph.D. at the Netherlands Institute for Brain Research in Amsterdam, the Netherlands. In 1999 he joined the laboratory of Dr. W. Mobley at Stanford University.

Dr. Salehi is investigating how certain cholinergic neurons in the Down syndrome brain degenerate. These cells play an important role in learning, memory, and attention. Dr. Salehi believes that degeneration of these cells is caused by disruption of transport of a protein called nerve growth factor (NGF). Lack of NGF hinders cell development and suppresses normal functions. Because NGF transport is abnormal, cholinergic neurons shrink and shut down their function. Dr. Salehi studies why and how these cells degenerate.

Using a mouse model of Down syndrome, Dr. Salehi has identified a segment of the extra chromosome that is responsible for the degeneration. The next step is to find out exactly which genes are responsible.

Dr. Salehi and his research assistant Ryoko Takimoto are using novel techniques to study the activity of specific genes located on the identified chromosomal segment. By studying one gene at a time, Dr. Salehi will identify the ones responsible for degeneration. This will allow him to target these genes for treatment. His highest priority is improvement of learning and memory to prevent degeneration.

More information on Dr. Salehi’s research:

 

Parents and children are making a difference

We would like to introduce two funding initiatives created by proactive parents in the Down syndrome community – the Down Syndrome Research and Treatment Foundation and the Adopt-A-Mouse Campaign.

  • The Down Syndrome Research and Treatment Foundation
    Who and what is this Foundation? Several parents, who felt the need to support Down syndrome research, created this Foundation. The Foundation funds scientists and clinicians whose research shows promise in improving our understanding of Down syndrome and its treatment. More specifically, the Foundation supports research that contributes to improving brain function in people with Down syndrome. Our Center for Research and Treatment of Down syndrome is supported in part by this Foundation.
  • Adopt-A-Mouse Campaign
    A group of parents and their children has come up with a very creative Down syndrome research fundraiser: For $21 you can purchase a cute stuffed mouse – a symbol for the Down syndrome mouse models used in the laboratory. It makes a perfect a gift for a newborn baby or a child’s birthday and at the same time supports a worthy cause. The proceeds will directly support Down syndrome research.

 

A group at Johns Hopkins University reports that the Down Syndrome Critical Region may not be sufficient to produce trisomy 21 phenotypes

The Down Syndrome Critical Region (DSCR) is a segment on chromosome 21 which when triplicated is thought to be responsible for many phenotypes found in Down syndrome.  The DSCR hypothesis states that genes on this chromosomal fragment are necessary for the production of many characteristics of Down syndrome, including facial features.

To find out how much the genes in the DSCR contribute to the distinct facial features in Down syndrome, Olson, Reeves and colleagues created and compared several Down syndrome mouse models.  For each of these mice, Olson et al. measured various distances between different points on the skull and face, and compared them with each other, against normal mice and to data from people with Down syndrome.  The results were quite unexpected: Compared to normal mice, three of the four different mouse models had significantly smaller craniofacial features, including a model with only one copy of the DSCR.  In contrast, the mouse model that had three copies of just the DSCR had an increased skull size and larger craniofacial features compared to normal mice.  These results led the authors to conclude that triplication of genes in the DSCR region does not cause specific phenotypes, and that teasing out and understanding the causes of various phenotypes found in Down syndrome is more complex.

What do these results and conclusions mean for future Down syndrome research?  Contrary to what was hypothesized, the genes responsible for this particular phenotype (facial features) are not located in the DSCR, but somewhere else on chromosome 21. However, this does not mean that the DSCR is not important for Down syndrome.  Many essential genes are located in this region, such as genes thought to be involved in cognition and cognitive decline.  The DSCR hypothesis may not hold true for craniofacial features, but it may nevertheless hold true for many other phenotypes.

You can find an abstract of this interesting paper at PubMed.

Olson, L.E., Richtsmeier, J.T., Leszl, J., and Reeves, R.H. A Chromosome 21 Critical Region Does Not Cause Specific Down Syndrome Phenotypes. Science (2004) 306: 687- 690.

 

News from recent events

June 2004, Washington, DC
Expert Workshop on Biology of Chromosome 21 Genes: Towards the Gene-Phenotype Correlations in Down Syndrome.

The goal of this international conference was to promote communication between researchers working to understand the function of individual genes located on human chromosome 21, and the broader Down syndrome research community. Revealing the biological function of these genes will help to better understand how they might contribute the Down syndrome-related phenotypes such as cognitive impairment, heart malformations, and immune system defects. Combining this knowledge with insight obtained from mouse models of Down syndrome will allow Down syndrome researchers to identify cellular pathways at risk, and develop strategies for treatment. Researchers from the Center for Research and Treatment for Down Syndrome, including Dr. M. Blank, participated in this meeting.

July 17-22, 2004, Philadelphia, Pennsylvania
The 9th International Conference on Alzheimer's Disease and Related Disorders. The world's leading research forum on dementia was attended by a record number of researchers in the field. Over 4,200 scientists presented and discussed their most recent findings on Alzheimer's disease research and related disorders. Dr. A. Salehi and several other scientists from our Center attended and presented at this meeting.