Category Archives: Research Topics

Q&A With Dr. William Mobley

mobley-headshotDid you attend our webinar in January and ask a question that wasn’t answered? Dr. William Mobley has the answers!

Dr. Mobley from the University of California, San Diego’s Down Syndrome Center for Research and Treatment and Dr. Jamie Edgin from the University of Arizona’s Down Syndrome Research Group spoke at our webinar on January 29, 2015. Thank you, Dr. Mobley and Dr. Edgin – and all the people who attended the webinar. To listen to a copy, please click here.

What is the number of copies of APP with typical Trisomy 21?

The answer is 3.  This is due to the presence of an extra copy of the entire 21st chromosome, which harbors the gene for APP and as many as 500 other genes.

Would inhibiting DYRK1A be beneficial?

Quite possibly.  What is not clear at present is exactly what changes in the Ds brain are due to the extra copy of the gene for this protein. What we do know is that it is an enzyme that acts on a number of neuronal functions and that an increase in the amount of this protein is likely to cause changes that impact normal function. A number of labs are working on this problem, including ours [UC San Diego Down Syndrome Center for Research and Treatment], and more data should be coming forward in the next few years. An ongoing trial of a non-specific inhibitor of this protein may provide important insights into what might be accomplished by creating treatments that would reduce its levels or effects.

What ages could benefit from the therapies that were discussed?

A good question.  Our studies and others focused on increased inhibition might well lead to treatments that would be given to children.

Our studies on APP target age-related changes in neurons and logically would be administered to adults.  But since the problems that an increased number of the APP gene causes are already detected in young people, we envision that such treatments may ultimately also be given to children.

The vaccine that targets a product of APP that I discussed will be first be administered to adults but then might well used in young adults and possibly children.

Can you tell us more about endosomal enlargement – timing, APP dose-dependence and tests?

Endosomal enlargement is indeed present in the very young brain and is a direct consequence of increased levels of APP. It is almost certainly seen in all people who have the full Trisomy 21.  The test for this would therefore be the test which shows whether or not someone is a full or partial trisomy. More sophisticated tests aimed at defining the number of APP genes present in the genome would also be useful, but I would suggest that the simply karyotype test should suffice for almost everyone with Down syndrome.



Scientific Advisory Board Meeting – February 2015

researchThe core of the LuMind Foundation’s successful research program is our Scientific Advisory Board (SAB), comprised of the brightest minds in research across disciplines and from around the world. Lead by our Chief Scientific Officer, Dr. Michael Harpold, the SAB met in person in mid-February to guide the organization’s mission to fund the most promising lines of discovery.

“Thank you to all the members of the LuMind SAB for volunteering their time from their very full schedules to attend the SAB meeting,” said Dr. Harpold. “We value their thoughtful expert perspectives and contributions in reviewing the progress of the current LuMind-supported research and strategic research directions to further advance and accelerate progress.”

The SAB continues to be enthusiastically unified that the LuMind Foundation Research strategy, program, and grants continue to be remarkably successful and transformative for Down syndrome cognition research and its potential for creating significant and meaningful new opportunities for children and adults with Down syndrome.

The SAB meeting and discussions provide a foundation for the next steps in further assessing research projects and developing recommendations for the next new 2015-2016 LuMind Foundation Research Grants.

Truly heartfelt thanks and appreciation for each of the SAB members for their continued dedication to working with the LuMind Foundation to continue to advance critical, influential and game-changing new Down syndrome cognition research.

Members of the SAB are:

  • Michael M. Harpold, PhD, Chair – Scientific Advisory Board and Chief Scientific Officer
    LuMind Foundation
  • Ronald M. Evans, PhD, Professor and March of Dimes Chair in Molecular and Developmental Biology, Gene Expression Laboratory, Salk Institute for Biological Studies
  • Leslie Leinwand, PhD, Professor, Molecular, Cellular and Developmental Biology, University of Colorado
  • Lynn Nadel, PhD, Regents’ Professor of Psychology, University of Arizona
  • Roger Harper Reeves, PhD, Professor, Department of Physiology, Johns Hopkins University
  • André Strydom, MBChB, PhD, Senior Clinical Lecturer, Intellectual Disabilities and Mental Health Sciences Unit, University College London

You can read more about the SAB on our website, including more about our SAB members.

FAQ: Isn’t Down syndrome too complex to treat?

Young girl smilingFor many years, scientists believed that Down syndrome was too complex to understand, and they believed that there was no way to reverse or reduce the severity of cognitive impairment. However, via two distinct approaches, over the last decade scientists have made unprecedented progress towards identifying a treatment to ameliorate the cognitive impairment associated with Down syndrome.

The first approach is based on genetics.  Scientific advances have made it possible to understand how specific genes are linked to specific abnormalities in the structure and function of the brain. Although the 21st chromosome has hundreds of genes, researchers believe that there may be only a handful that significantly impact cognition. Using advanced techniques and methods, researchers believe they will be able to isolate the effects of these specific genes and determine how their expression in the brain can cause problems with cognition.

The second approach is to study the endpoints of brain structure and function in mouse models. By investigating the physical differences and the resulting functional impacts, researchers are able to define specific mechanisms responsible for cognitive dysfunction.  Once these are established, they can begin the process of discovering treatments that enhance brain function, including cognition.

Today Down syndrome is not too complex to understand and it is not too difficult or too late to treat.

– From the Frequently Asked Questions portion of our website. Read more answers to other frequently asked research questions. 

If you have general questions about Down syndrome cognition research, send an email to or fill out the form below.


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.


NIH Releases 2014 Research Plan

DS Directions PlanWe’re very pleased to announce that NIH has just released the updated document “Down Syndrome Directions,” the NIH Research Plan on Down Syndrome. The research plan will provide another great way to work with the DS community to further research efforts.

“In succeeding the previous NIH Plan for Down Syndrome released in late 2007, ‘Down Syndrome Directions’ represents a very important plan for Down syndrome research,” said Dr. Michael Harpold, LuMind’s Chief Scientific Officer and also chair of the DS-Connect® Governance Board. “The plan builds on the very dramatic research progress and incorporates significant new directions to address the health of children and adults with Down syndrome.”

‘Down Syndrome Directions’ was developed with input from the entire Ds community and the many comments and ideas were compiled by the NIH staff.

Added Dr. Harpold, “We especially thank NIH for their sincere consideration and incorporation of the many feedback comments from those in the Down syndrome community, including individuals, organizations and the researchers and clinicians. We look forward to continuing to work together with the NIH, and all of the community, in implementing this plan and furthering significant progress in creating new opportunities for all children and adults with Down syndrome.”

To read or download a PDF of “Down Syndrome Directions,” visit NIH’s publication page.

For more information on the DS-Consortium, please visit their webpage.

Sweet Dreams for Sleep and Cognition Researchers

Jamie EdginOur congratulations to Dr. Jamie Edgin, a LuMind Foundation supported researcher, upon her award of funding for infant sleep to begin the “Arizona Sweet Dreams Study.” Edgin and her co-principal investigator Caron Clark will be exploring the link between infants’ early sleep quality and later cognitive development.

Dr. Edgin’s LuMind-funded sleep assessment studies have shown that sleep quality in toddlers and school-age children with Down syndrome is strongly correlated with language development.

Congratulations Jamie and Caron!

Read more on the University of Arizona website.



For today’s Throwback Thursday, we look back just a few months ago to World Down Syndrome Day at the United Nations on March 21, 2014.


Enjoy all the talks or fast forward ahead to about 2:34.12 for the Down syndrome cognition research portion of the day’s talks moderated by LuMind Executive Director Carolyn Cronin with presentations from:

  • Dr Yvonne Maddox, NICHD – Down Syndrome Research and Advocacy: Improving Lives Together
  • Dr William Mobley, University of California San Diego – Enhancing cognition in people with Down Syndrome
  • Professor Antony John Holland,  University of Cambridge – Understanding the link between Down syndrome and Alzheimer’s disease: developing preventative treatments
  • Debora Seabra, Self-Advocate – Healthcare must be inclusive – Article 25 of UN Convention on the Rights of Persons with Disabilities


Clinical Trials UPDATE: Roche Initiates RG1662 Phase II Clinical Trials for Individuals with Down syndrome

LuMind Foundation-supported research has led to clinical trials currently in progress to address developmental cognitive deficits and those impairments associated with Alzheimer’s disease.

Roche, a leader in innovative research-focused healthcare and the world’s largest biotech company, has initiated a new multi-national Phase II clinical trial to evaluate the efficacy and safety of RG1662 in adolescents and adults, ages 12-30 years old, with Down syndrome. Following the successful completion of the previous groundbreaking Phase I clinical trial with this new drug that is being developed to address the cognitive and behavioral deficits in individuals with Down syndrome, this new significantly larger Phase II trial is a randomized, double-blind, placebo-controlled clinical study in which participants will be randomized to receive RG1662 either at low or high dose or placebo orally twice daily for 26 weeks.

This new trial, “A Study of RG1662 in Adults and Adolescents with Down Syndrome (CLEMATIS)”, will be conducted at multiple sites across the US, including La Jolla, CA, Sacramento, CA, Decatur, GA, Chicago, IL, Baltimore, MD, Boston, MA, Durham, NC, Dallas, TX, Salt Lake City, UT, and Madison, WI. In addition, the trial will be conducted at multiple international sites, including UK (4), France (4), Spain (3), Singapore (1), New Zealand (3), Canada (1), Mexico (5) and Argentina (2).

Visit our research section to learn more about the Phase II Roche clinical trial and other clinical trials.

The Connection between Ds and Alzheimer’s Disease

All adults with Down syndrome over 35-40 years of age develop the characteristic Alzheimer’s neuropathology, including the formation of beta-amyloid plaques, with earlier onset of dementia developing in more than 70% of individuals. Read more from a Science Daily article  and review the connections to the greater Alzheimer’s community.

DS Research 101: Part 1

New to the idea of Down syndrome research and treatment? Or just want to brush up on your knowledge? Here are some common questions we hear. This is part 1, in which we take a quick look at DS cognition research in general.

What is Down syndrome?
Down syndrome is a genetic condition caused by an error in cell division that occurs at conception. It entails an extra copy of the 21st chromosome; a person with DS has 47 chromosomes instead of the usual 46. This extra genetic material disrupts the normal course of fetal development, resulting in certain common physical signs and other less predictable traits: the extra chromosome can cause a wide range of health problems, and produces varying degrees of intellectual disability.

For most people with Down syndrome, cognitive impairment falls in the mild to moderate range, and they experience speech and language difficulties. This particular aspect of Down syndrome — cognition, the process of acquiring knowledge — is what our research addresses.

Isn’t Down syndrome too complex to treat?
Many of the physical problems associated with DS are already being treated; heart defects can be repaired surgically, for example, and poor vision and hearing can be improved through fairly simple means. Treating the cognitive effects of DS — reducing the severity of impairment in an individual and improving overall function — is admittedly a more complicated proposition.

Still, we believe it can happen. Over the last decade, scientists have made exciting strides toward that goal. The DS cognition research we promote is currently following two promising avenues of inquiry:

The genetics-based approach.We now understand how specific genes correspond to specific abnormalities in brain structure and function. Although each chromosome carries hundreds of genes, researchers suspect there may be only a handful of those that significantly affect cognitive ability. Once researchers have isolated the effects of that particular handful, we can begin to determine how the expression of those genes causes problems with cognition — an essential step in developing effective therapies.

The mouse model approach. To understand the physical differences of the brain affected by DS and the resulting functional impact, researchers look to the mouse. In general terms, the process involves examining mice with Down syndrome — yes, really — to identify which specific mechanisms in the brain are responsible for cognitive impairment; as these mechanisms are established, scientists can begin to pursue appropriate treatments.

The diligent work of these researchers is already proving that Down syndrome isn’t too complex to understand. Based on their results so far, we predict that it’s not too complex to treat, either.

So does treating DS mean a cure?
No, once a child with DS is conceived, the extra chromosome is there to stay. Still, eventually we may able to reverse or improve the cognitive deficiency it causes. No one can say for sure how much of an improvement we can hope for, but even a modest increase of 15 IQ points could have a profound impact on the life of someone with Down syndrome. For those who are mildly or moderately impaired, meaning the majority, those extra 15 points could mean greater independence and fulfillment in school and in the workplace. We’re not proposing a cure for Down syndrome. We’re working toward the promise of greater opportunity — and a more secure future — for the people who have it.

In part 2 we’ll talk about our organization’s specific research objectives. In the meantime, we’d be happy to take on any questions you have about DS research and treatment — do let us know what you’d like to know, and join us again next week as we continue the conversation.

Image adapted from the Genome Management Information System, Oak Ridge National Laboratory.