Tag Archives: research

Comments on Reports of a “New Down Syndrome Therapy”

By Dr. Michael Harpold
Chief Scientific Officer, LuMind RDS Foundation

Many of you have asked about a recent news piece and associated press release entitled “New Down syndrome Therapy Discovered.” Although this is not a research endeavor LuMind RDS is funding, the following perspective is provided which may be helpful in addressing some questions and further understanding the underlying research study and its potential as described in a scientific journal and associated press release.

First, I’d like to point out that, in my view, the title of the press release is misleading and factually inaccurate regarding the underlying research and results. As we all know, often press release titles represent an attempt to draw in readers with a few succinct words, but frequently over-hypes the underlying story. At this point, neither the body of the press release nor the underlying scientific publication demonstrate the research or results as any actual near-term or potential therapy. Application as a possible therapy or therapeutic approach in individuals with Down syndrome, if any, would likely be quite limited and many years into the future and require extensive additional research.

The following represents a brief scientific perspective on the study, as recently published in the scientific literature:

  • The researchers describe an approach for introducing a gene, designated ZSCAN4 (a gene located on human chromosome 19) or a laboratory-modified form of its RNA product into (and resulting expression of the ZSCAN4 protein in) either mouse embryonic stem cells (which have abnormal numbers of chromosomes generated during cell culture maintenance and growth in the laboratory, but not derived from any mouse model for Ds) or human Trisomy 21 fibroblast cells, all maintained and grown in the laboratory in Petri dishes, i.e., in vitro cell culture, meaning not in a living laboratory animal or human.
    • The scientific data indicate that the approach results in loss of the extra chromosome(s) in a limited proportion of the cells grown in culture in the laboratory. Although the researchers state that the approach is “highly efficient” in reducing extra chromosomes in the cells, the actual results demonstrate that, while a significant change, it is arguably still a relatively low percentage. For any potential therapeutic application in humans the efficiency would likely be required to be very much higher and technically quite challenging and difficult to control.
    • It should also be noted that the actual biological function(s) of ZSCAN4 remains unclear and under continuing scientific investigation, although some other previous research results suggest it may be involved in certain chromosome and/or cell maintenance functions.
  • The published scientific study does not describe the application of the approach to a living laboratory animal, so it is impossible to assess or determine whether there would be any effect (therapeutic, side effects or otherwise), positive or negative, in a whole organism (laboratory animal or human) which would represent a potential therapy. Demonstration of potential therapeutic benefit/efficacy, and lack of any problematic side-effects, in a living laboratory animal model will be required for this approach to be considered a realistic potential therapy.
    • There will be significant technical challenges in potential application to a whole lab animal model, much less humans, and it is further quite challenging to imagine in the foreseeable future how the approach could potentially address treatment/improvement of cognitive function, including Alzheimer’s disease, in the brain in a person with Ds.
    • Given that the described approach results in loss of extra chromosomes at least in some cells grown in culture outside the body, it is possible to conceive that it might potentially be applied to “auto”-transplantation-type therapies (transfer of the treated animal’s own cells back into the animal) that might address certain blood or immune disorders, but not extend to any other organ systems or cells in the body. However, this will require considerable additional research to demonstrate such potential.

Overall, the scientific research is interesting and otherwise could lead to further insights on chromosomal or cell maintenance and functions generally as well as in Ds. This is a research area among a very broad range of other areas that will continue to be monitored. However at this stage, this research study and associated approach would not represent a  research area closely relevant to further understanding cognition or development of an associated practical cognitive or Alzheimer’s therapeutic in Ds.

Dr. Harpold at the NIH Alzheimer’s Disease Research Summit 2015

We appreciate Dr. Michael Harpold for being such a road warrior on behalf of the Down syndrome community.

On February 9-10, 2015, Dr. Harpold, LuMind Foundation’s Chief Scientific Officer, attended the biennial NIH Alzheimer’s Disease Research Summit 2015, a major forum for the dynamic development of coordinated Alzheimer’s disease research efforts under the Congressionally-mandated National Alzheimer’s Plan.

As stated on the NIH website, the central goal of the AD Research Summit 2015 is to continue the development of an integrated multidisciplinary research agenda necessary to address critical knowledge gaps and accelerate the discovery and delivery of efficacious treatments for AD patients at all stages of disease.

Attending this conference provides an additional major forum to increase support and advocacy for greater inclusion of research on Alzheimer’s disease in individuals with Down syndrome and its contributions to a deeper understanding of Alzheimer’s disease and the development of effective new therapeutics, not only for individuals with Down syndrome, but everyone.

For more information about the summit including access to webcasts of the two-day event, please visit the NIH website.

A Research Story: Fragile X

On National Public Radio, there was a story about a foundation started by concerned parents, funding impressive discoveries, results of clinical trials, and the quest for new avenues of research. Nope, not the LuMind Foundation (or even our former name Down Syndrome Research and Treatment Foundation). This is a story about fragile X.

fragilex-1_NPRThe NPR piece, ‘A Family’s Long Search For Fragile X Drug Finds Frustration, Hope’ highlights the family of a 25-year old man with fragile X. In 1994, his parents helped start the FRAXA Foundation to ignite research into fragile X. Recently, their son participated in a clinical trial that came about in part thanks to a researcher FRAXA had funded.

There are so many similarities between the journey of these parents of a young man with fragile X and our own quest to find drug therapeutics to improve cognition for people with Down syndrome. Change a few words, a few names, and this could be the Down syndrome community or the CF world, or MS or ALS.

This article illustrates the realities of research, the hopes and frustrations and lessons learned from each step in the research and clinical trial process. The positive force achieved from collaboration between the community, researchers, and biopharma companies also mimics our journey and approach.

Perhaps most importantly, this story underscores the importance of funding research because even when there aren’t immediate positive results, what is learned may open the doors to other discoveries.

Thank you for your support of cognition research.


Local Association Support of Down Syndrome Cognitive Research is Growing

An encouraging development is that local associations are adding research support to their program services. Sizable contributions to RDS and Down syndrome cognitive research have been made by Alexander’s Angels of Long Island, Northern New Jersey Down Syndrome Alliance, Down Syndrome Association of Greater Charlotte, Down Syndrome Association of Central Texas and Greater Clear Lake Families Exploring Down Syndrome. Thank You!

When all associations across the country begin following this lead, national support for Ds research will be fundamentally re-stated, leading to significant increases in funding and even more rapid progress of this remarkable medical initiative.

RDS can assist your organization in making a commitment to support research. Please reach out to RDS at info@researchds.org . It would be a privilege to meet with your association members and share the exciting progress of Down syndrome cognitive research.
Thank you so much for your continued assistance to the Down syndrome community!

Research Down Syndrome Presents Light the Way Award to Dr. Roger Reeves and Dr. Yvonne Maddox at Washington, DC Tribute 21 Event

The Research Down Syndrome (RDS) Foundation presented its 2013 Light the Way Award to Dr. Roger Reeves from the Johns Hopkins University School of Medicine and Dr. Yvonne Maddox from the National Institute of Child Health and Human Development at Tribute 21, the First Annual Masquerade Ball benefiting RDS. The award recognizes persons engaged in initiatives to assist individual empowerment. Previous award winners have included New Jersey First Lady Mary Pat Christie, Newark Mayor Cory Booker, and F. Hoffmann-La Roche Vice President Dr. Luca Santarelli.
Dr. Reeves, Professor in the Department of Physiology and the Institute for Genetic Medicine at the Johns Hopkins University School of Medicine, was recognized for his research which focuses on the mechanisms of gene action in Down syndrome. His efforts have contributed to significant breakthroughs in the field of Down syndrome cognitive research.
Dr. Yvonne Maddox, Deputy Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development has led initiatives to establish the National Down Syndrome Consortium and the National Down Syndrome Patient Registry.
The awards were presented November 9, in Washington, DC at Tribute 21, a fundraising ball hosted by Erin and Brendan Fry in memory of their son, Flynn Thomas Fry. The event supports scientific research that will, as Mr. and Mrs. Fry noted, “enhance life opportunities of all the loved ones with Down syndrome whom we are still so blessed to have in our lives.”
At the event, Research Down Syndrome recognized the contributions of Drs. Reeves and Maddox, and expressed its appreciation to Mr. and Mrs. Fry, the sponsors, the host committee and all of the guests for their belief in the promise of Down syndrome cognitive research. The Foundation noted that support through donations and events such as Tribute 21 has contributed to rapid progress in this remarkable research initiative. RDS grants and other support has led to the initiation of three clinical trials currently underway that are evaluating potential therapies to improve cognition in individuals with Down syndrome and address the increased likelihood of Alzheimer’s disease.
The featured speaker at the event was self advocate Mr. Eli Lewis. Mr. Lewis spoke about his journey through the public school system and his transition to adulthood. Mr. Lewis is currently employed at Project Search.
In addition to Mr. Lewis’ speech, the over four hundred attendees enjoyed music from the 19th St. Band and participated in an auction, which included a painting of the Jefferson Memorial produced live at the event by local artist Maggie O’Neill.

Research Down Syndrome Announces 2013/2014 Grant Awards to Fund Down Syndrome Cognitive Research

Research Down Syndrome (RDS) has announced funding for five grants to support Down syndrome cognitive research.

RDS is committed to supporting the identification of the causes of the intellectual impairments associated with Down syndrome and to facilitating the development of pharmacological therapies to improve memory, learning and communication in persons with Down syndrome, and to address the increased likelihood of Alzheimer’s disease. Encouraging progress has been made over a very short time. Three human clinical trials are underway, less than a decade after the support of private foundations stimulated the progress of Down syndrome cognitive research.

Research Down Syndrome, among the leading sources of private funding for Down syndrome related cognitive research, prioritizes funding towards programs with a high probability of readily contributing to the development of safe and effective therapies.  Continued private donations are needed to support the constantly expanding research efforts that will lead to potential medical treatments.

The 2013/2014 RDS Research Grants include:

Johns Hopkins University School of Medicine: RDS Research Center Grant entitled “A Down Syndrome Virtual Center for Basic and Translational Studies-Cognition and Therapy in Down Syndrome”    

University of California, San Diego School of Medicine: RDS Research Center Grant entitled "Defining the Genes and Mechanisms and Treatments for Neurodevelopmental and Neurodegenerative Causes of Cognitive Dysfunction in Down Syndrome"

University of Arizona: RDS Innovation Research Grant entitled The Neuropsychology of Down Syndrome”

Stanford University School of Medicine: RDS Innovation Research Grant entitled “Mechanisms Underlying the Roles of Sleep and Circadian Rhythms in the Learning Disability of Down Syndrome”

VA Palo Alto Health Care System: RDS Innovation Research Pilot Grant entitled “Improving Adrenergic Signaling for the Treatment of Cognitive Dysfunction in Down Syndrome”

Detailed information on these grants can be found here.

Faulty Stem Cell Regulation may contribute to Cognitive Deficits Associated with Down Syndrome

Research Down Syndrome grantee Dr. Craig Garner was co-author of a just released paper out of Stanford University. The report described studies using both human skin cells and the Down syndrome mouse model Ts65Dn in deciphering the impact of a gene named Usp16 on stem cell growth. (Stem cells are unspecialized cells that renew themselves and function as a primal source of tissue or organ specific cells with special functions.) The gene Usp16 is found on human chromosome 21 and thus in triplicate copy in persons with Down syndrome. In experiments testing human cells, researchers discovered that an excess of Usp16 in cells from people without Down syndrome caused skin cells to grow more slowly. Also, reducing Usp16 in skin and nerve cells in people with Down syndrome allowed the cells to have normal growth patterns rather than to regenerate slowly.

In the model study using the Ts65Dn mouse with gene Usp16 in triplicate, researchers found that neural stem cells from the mice were less able to self-renew and grow normally than were cells from mice with a duplicate copy. When the researchers reduced the expression of Usp16 in the cells from the Ts65Dn mice to more normal levels, these functional defects were largely corrected. Dr. Garner said that the extra copy of chromosome 21 and the Usp16 gene may speed up the rate that stem cells are used during early development, exhausting the stem cell pools needed to regenerate tissues as adults. Dr. Garner stated further, "This study suggests that drug-based strategies to slow the rate of stem cell use could have profound effects on cognitive function, aging and risk for Alzheimer’s disease in people with Down syndrome".

Michael Clark M.D. was senior author of this paper.

More information on this interesting study may be found in this release issued by Stanford University: