World’s First Clinical Trial for anti-Abeta Vaccine Targeting Alzheimer’s Disease-like Characteristics in People with Down Syndrome

PRESS RELEASE – Issued by AC Immune

• Studies AC Immune’s ACI-24, the first anti-amyloid vaccine for treatment of Alzheimer’s disease-like characteristics in people with Down syndrome
• Clinical Study is done in collaboration with University of California San Diego
• US NIH provides significant funding with an additional grant from the LuMind Research Down Syndrome Foundation
• Alzheimer’s disease-like characteristics develop in virtually all people with Down syndrome over age 40; majority develops associated dementia over
  age 60

Lausanne, Switzerland, San Diego, CA and Marlborough, MA USA – January 7, 2016 – Today plans were announced to conduct the world’s first clinical trial for a vaccine targeting Alzheimer’s disease-like characteristics in those with Down syndrome. The study will test AC Immune’s vaccine ACI-24 and is being conducted in collaboration with the University of California, San Diego (UC San Diego) Down Syndrome Research and Treatment Center. Funding is provided by a significant grant from the US National Institutes of Health (NIH) and an additional grant from the LuMind Research Down Syndrome Foundation. This is the first public/private collaboration for a clinical trial in the field of Down syndrome.

Individuals with Down syndrome (DS) have an extra copy of chromosome 21 which carries the gene for APP encoding the precursor protein of Abeta, one of the hallmarks of Alzheimer’s disease (AD). An important consequence is that individuals with DS develop AD-like characteristics at a rate three to five times greater than that of the general population and at a much younger age. Further, AD-like characteristics develop in more than 98% of people with DS over age 40 with up to 80% developing associated dementia over the age of 60. It is estimated that there are 6 million people with DS worldwide, with 400,000 in the United States.

Trial participants will be adults with DS. The objectives of the trial include studying safety and tolerability of ACI-24, its effect on induction of antibodies against Abeta, clinical and cognitive measures in adults with DS and its effect on biomarkers of AD-like pathology in DS. Participants in the study will be treated for 12 months, with 12 months follow up.

Prof. Andrea Pfeifer, CEO of AC Immune said: “We are very pleased to bring this potentially disease modifying treatment for Alzheimer’s disease into the vulnerable, genetically predisposed Down syndrome population. The combined knowledge and resources of AC Immune, UC San Diego, NIH and the LuMind Research Down Syndrome Foundation should generate much needed insight for treating the Alzheimer’s-like characteristics of those with Down syndrome. Additionally, this ground-breaking clinical trial could enhance our understanding of early intervention and prevention of Alzheimer’s in general.”

Dr. William Mobley, Executive Director of the UC San Diego Down Syndrome Research and Treatment Center, commented: “We are delighted to join our colleagues at AC Immune and the LuMind Research Down Syndrome Foundation in this exciting study, the first step in a process whose ultimate goal is preventing Alzheimer’s disease in people with Down syndrome.  That both public and private funding sources support the study signifies the importance attached to Alzheimer’s disease and the valuable insights that will come from studies of this disorder in Down syndrome.  We wish to thank our colleagues as we eagerly look forward to helping people with Down syndrome and their families and loved-ones.”

Dr. Michael Harpold,  LuMind Research Down Syndrome Foundation’s Chief Scientific Officer, stated: “We are very excited the LuMind Research Down Syndrome Foundation has been able to work and join together with AC Immune, UC San Diego and NIH in establishing the first ever private-public partnership for a clinical trial in the field of Down syndrome. Accelerating research and the development of new potential therapies to address the developmental intellectual disabilities and earlier onset of Alzheimer’s disease in people with Down syndrome represents a major part of our foundation’s mission and commitment to prevent the earlier decline and loss of important gains they have attained throughout their lives.”

About ACI-24

ACI-24 is a liposomal therapeutic anti-Abeta vaccine candidate, which is owned by AC Immune and was discovered utilizing the Company’s proprietary SupraAntigen^TM technology platform. The vaccine is designed to stimulate a patient’s immune system to produce antibodies that specifically target the oligomeric and fibrillary Abeta proteins to prevent beta amyloid plaque accumulation and to enhance plaque clearance. Preclinical data demonstrated a significant activity in plaque reduction and memory restoration as well as a favorable safety profile characterized by a lack of local inflammation and a mode of action independent of inflammatory T-cells. The vaccine is currently also being studied in a phase 1/2a clinical trial in patients with mild to moderate AD, in which no significant safety issues have been detected to date.

About Down syndrome

Down syndrome, or trisomy 21, is the most common genetic cause of intellectual disability and developmental delay, and affects one in 700 newborns. This condition results when an individual has three, rather than two, copies of the 21st chromosome. This additional genetic material causes impairment of cognitive ability and physical growth, and is associated with other medical issues ranging from neurological and cardiac defects to hearing and vision problems as well as earlier development of Alzheimer’s disease. The average life expectancy for people with DS has increased from 25 years in the 1980’s to approximately 60 years today.

About Alzheimer’s disease

It is becoming increasingly clear that Alzheimer’s disease develops because of a complex series of events that take place in the brain over a long period of time. Two proteins – Tau and beta-amyloid (Abeta) – are recognized as major hallmarks of neurodegeneration: tangles and other abnormal forms of Tau protein accumulate inside the brain cells and spread between cells, while plaques and oligomers formed by beta-amyloid occur outside the brain cells of people with AD.

AD is one of the biggest burdens of society with a dramatic and growing worldwide incidence rate of one new case every three seconds, or 9.9 million new cases of dementia each year. Since the incidence and prevalence of AD increase with age, the number of patients will grow significantly as society ages. Worldwide in 2015 there are 46.8 million people living with dementia and by 2050 it is expected that global patient numbers will triple to 131.5 million. It is estimated that the annual societal and economic cost of dementia has risen from US$ 604 billion in 2010 to US$ 818 billion in 2015.  In the US, AD is now the 6th leading cause of death across all ages and is the fifth leading cause of death for those aged 65 and older.

About AC Immune

AC Immune is a leading Swiss-based biopharmaceutical company focused on neurodegenerative diseases with three product candidates in clinical trials.  The Company designs, discovers and develops therapeutic and diagnostic products to prevent and modify diseases caused by misfolding proteins. AC Immune’s two proprietary technology platforms create antibodies, small molecules and vaccines to address large markets across a broad spectrum of neurodegenerative indications. Alzheimer’s disease (AD) is the largest indication addressed by its products but the company’s innovative, differentiated and disease-modifying therapies are designed to shift the paradigm in the treatment of other neurodegenerative diseases such as Parkinson’s, Down syndrome, and Glaucoma. The Company has a large, diversified and promising pipeline featuring seven therapeutic and three diagnostic product candidates. The most advanced of these is crenezumab, an anti-Abeta antibody that is licensed to Genentech entering phase 3 clinical trials. Crenezumab was chosen by the US National Institute of Health for use in the first-ever AD prevention trial. The company has partnered three programs targeting Tau: ACI-35 with Janssen (therapeutic vaccine, phase 1b), Tau-PET imaging agent with Piramal (Alzheimer’s diagnostic agent) and anti-Tau-antibodies with Genentech (preclinical). The anti-Abeta vaccine ACI-24 phase 1/2a trial is run in house.

About UC San Diego Down Syndrome Research and Treatment Center

Established in 2009, the Center’s efforts focus on defining the genes and mechanisms responsible for the cognitive challenges faced by people with Down syndrome. Studies are carried out in both mouse models and in mouse and human cellular models.  The insights derived support translation of basic science findings into new treatments, using either existing drugs or through drug discovery. The Center’s work has resulted in conceptual innovations and several novel treatment targets and has inspired existing trials as well as the clinical study announced in this press release (supported by an NIH grant under award number R01AG047922). The Center is supported by the NIH and private foundations, including the LuMind Research Down Syndrome Foundation, the Alzheimer’s Association, the Tau Consortium and the Cure Alzheimer Fund.

About LuMind Research Down Syndrome Foundation

LuMind Research Down Syndrome Foundation, formerly the Down Syndrome Research and Treatment Foundation (DSRTF) and Research Down Syndrome, is an international non-profit organization with headquarters in Marlborough, Massachusetts, aimed at accelerating the development of treatments to significantly improve cognition, including memory, learning and speech, for individuals with Down syndrome. LuMind RDS Foundation is the leading source of private funding supporting Down syndrome cognition research at major research centers, including Johns Hopkins Medicine, Stanford University, University of California, San Diego, and University of Arizona. Since its founding in 2004, LuMind RDS Foundation has committed more than $13 million to fund results-driven research programs that will benefit children and adults with Down syndrome, and has been instrumental in the initiation of clinical trials now under way.

For further information please contact:

AC Immune

Prof. Andrea Pfeifer Chief Executive Officer Phone: +41-21-693 91 21 E-mail:andrea.pfeifer@acimmune.com	Eva Schier Corporate Communications Manager Phone: +41-21-693 91 34 E-mail: eva.schier@acimmune.com
Nick Miles Senior Consultant Cabinet Privé de Conseils s.a. Mobile : +41 79 678 76 26 E-mail : miles@cpc-pr.com	In the US Ted Agne The Communications Strategy Group Inc. Phone: +1 781 631 3117 E-mail: edagne@comstratgroup.comed

 

UC San Diego

William C Mobley, M.D., Ph.D. Professor of Neurosciences, and Executive Director, Down Syndrome Research and Treatment Center Phone: +1 858-534-9434 Email: wmobley@ucsd.edu

Scott LaFee Director, Media Relations Marketing and Communications UC San Diego Health Sciences Phone : +1 619-543-6163 Email : mailto:slafee@ucsd.edu

 

LuMind Research Down Syndrome Foundation

Carolyn Cronin President/Chief Executive Officer Phone: (508) 630-2178 Email: ccronin@lumindrds.org	Ellen Oliver Marketing Director Phone: (508) 630-2179 Email: eoliver@lumindrds.org
Michael M. Harpold, PhD Chief Scientific Officer Phone: (520) 297-3105 Email: mharpold@lumindrds.org

 

What Do You Want to be When You Grow Up?

By Beth Gard Beth Gard is wife to Alan and mom to Gabe, Alijah, and Dalaney and leads Medical Outreach for the Down Syndrome Alliance of the Midlands. She is also Alan Gard’s caddie as he completes the Hundred Hole Hike to benefit LuMind RDS Foundation and Down syndrome cognition research.

What do you want to be when you grow up?  We have all been asked this question. We’re asked it as soon as we can speak and that’s usually as a toddler. And of course a toddler has an answer for that question!   This question is easy for our oldest son, Gabe. Since he could talk he has wanted to be a train engineer. He’s been obsessed with trains since he was a baby and right now he is equally obsessed with Legos.  Alan and I joke that he is our master builder train engineer. Alijah is starting to say words now (that’s very exciting for all of us). He can’t tell us yet what he wants to be, but based on his interests he wants to drive a backhoe loader or be a ball player. When you ask Gabe “whom” he wants to be when he grows up, he wants to be a dad. I assume that’s because he has an excellent role model for a dad. I wonder “whom” Alijah will want to be when he grows up…

As a parent of a child with special needs it’s hard not to think about your child’s future. When we first found out that Alijah had Down syndrome we were worried about everything, but we were particularly concerned about his future. From day one we were committed to giving him everything he needed and to make sure we had the same expectations for him that we had for Gabe. We want him to go to school, to go to college, to fall in love and most of all to lead a fulfilling life. But, for all of these milestones to occur for Alijah we need to advocate for him in all areas of his life. I do tend to focus on Alijah’s future probably more than I do on my other children’s futures. Since Alijah was three months old my main concern has been about school. Anyone close to me will tell you that I feel extreme stress when I think about school. It doesn’t matter if it is preschool or elementary school. I feel sick at times trying to make sure that we make the right decisions for Alijah. But in April, I attended one of our local Down syndrome organizations’ educational presentations by Dr. William Mobley, a neuroscientist from the University of California San Diego, a LuMind RDS funded researcher. Dr. Mobley came to speak to us about the links between Down syndrome and Alzheimer’s disease. He began by providing evidence that the brains of people with DS don’t function like those of typical people. This information wasn’t surprising since I see this everyday when Alijah is processing information or responds to requests and directions. Dr. Mobley also provided us with the evidence that the plaques that are characteristic of Alzheimer’s begin to develop at age 40 in individuals with DS. I also knew this, however, hearing it and seeing the data hit me hard. Maybe it was because I was a month away from turning 41. Maybe it was because it was a long day with Alijah and Dalaney (as most days are right now). Maybe it was a combination of a lot of things. I thought, “I’m 40 and for the most part I still feel like I am in my 20s.  I tend to forget things from time to time, but who doesn’t?” I started to wonder what Alijah will feel like when he is my age. What will his cognitive level be at 40?  And then the thoughts and scenarios started to snowball as they tend to do when something negative pops into my head. Then I started to think about who is going to take care of Alijah when he starts to experience this decline?  God willing, I’ll still be on earth, however I will also be nearing 80. I discussed this with a friend and she joked we would both be in the old folks home, demented together.  I laughed because I saw some humor in it (sometimes you just have to find the humor in even the most sad situations). Unfortunately, despite the jokes and lightheartedness that can be made of situations, this could happen. These thoughts have never occurred to me when I think about Gabe and our youngest child, Dalaney, when they reach 40.  I assume Gabe and Dalaney will be in the prime of their lives established in their careers, possibly married and/or raising children, hopefully happy and healthy. I wish sometimes these thoughts about Alijah would never come to me. I wish I had blinders on to the reality of what life could be for Alijah as things stand now.  I don’t want to imagine my son who is smart, fun, stubborn and nothing short of happy even when he is having what is his worst day not living a fulfilling life once he reaches middle age. The need for cognition research in individuals with DS is so important, not only to help improve their memory and learning ability while they are young, but also to develop drugs to help delay or even cure Alzheimer’s. Even though DS is one of the most common genetic conditions, it is one of the least funded for research. Organizations such as LuMind RDS and others are paving the way to raise funds for research and awareness that DS research is not only a necessity for the DS population, but the general population as well. As Alan embarks on his third hike I hope that you will consider donating to his team in the Hundred Hole Hike or perhaps start your own team and raise funds for research. Our cause isn’t just about raising awareness it’s about advocating for people with DS to make sure that research is being done to improve their cognitive quality of life. I look forward to the possibilities that cognitive research advances can offer to Alijah and others with DS to help them achieve their goals and to lead fulfilling lives. I am anxious to hear what Alijah wants to be when he grows up and helping him live out his dreams!

2015 Awards Gala: Remembering Bright Minds

For our first Awards Gala we wanted to honor the best and brightest and cognition research today, but also pay tribute to great minds who are no longer with us.

Dr. Edgin receiving the Dr. David R. Cox Rising Star award.

We awarded Dr. Jamie Edgin the Cox Rising Star Award. This award is named in honor of David R. Cox, M.D., Ph.D. a world-renowned geneticist and inaugural member of the LuMind Research Down Syndrome Foundation’s Scientific Advisory Board. Some of Dr. Cox’s significant professional accomplishments included:

• making instrumental contributions to the Human Genome Project
• serving as a professor of genetics and pediatrics at Stanford and co-director of the Stanford Genome Center
• participating in several international and national councils and commissions; and
• elected to the Institute of Medicine of the National Academy of Sciences.

Since Cox was always curious, innovative and a pioneer, the Cox Rising Star Award recognizes distinction in Down syndrome research by early career researchers.

Dr. Mobley receiving the Cohen Researcher of Distinction Award, named in honor of William I. Cohen, MD.

Dr. William Mobley received the Cohen Researcher of Distinction Award, named in honor of William I. Cohen, MD, a great friend, colleague, and very active and highly supportive inaugural member of LuMind RDS Foundation’s Scientific Advisory Board.

Bill Cohen was widely recognized for his deep compassion and contributions to the medical care of children with Down syndrome, and his unwavering commitment to, and support of, the entire Down syndrome community. His energy, joy for all of life, and enthusiastic excitement for the potential of the most rigorous new evidence-based biomedical research for creating new opportunities for all people with Down syndrome has been inspiring to researchers, physicians, as well as all in the Down syndrome community and beyond.

This award recognizes a major impact on accelerating the pace of Down syndrome research through open access, participation and collaboration.

See photos from the awards gala.

Down Syndrome Cognition Research: THE Most Important Opportunity

by Sarah Wernikoff

Sarah Wernikoff was honored with the Luminary Award at our inaugural recognition gala, the Sky’s the Limit. Sarah chaired the LuMind Foundation Board from 2012-2014 and served as a member of the board for seven years. She presented the following remarks on why LuMind Research Down Syndrome Foundation and Down syndrome cognition research are important to her. Thank you, Sarah, for your continued support and inspiration!

I feel very honored to be acknowledged in this way – particularly at the same event as Dr. Mobley — the original visionary behind this field of research, and Dr. Edgin. It’s only due to their genius, creativity and perseverance that we are all here today. I also want to thank the Whites who had the vision to make this organization possible, and who have done so much for this very important cause over the last decade.  And last, I can’t leave out Carolyn Cronin. The breath of fresh air that is carrying us into the future. Carolyn, thank you for your tireless commitment.

It’s ironic for me to be here in this way with Dr. Mobley, and Patty White, as they are the very two people who I first had contact with 11 years ago soon after my daughter Tate was born in October of 2003.

It’s still hard for me to talk about those early days, …but needless to say learning Tate had Ds was a complete shock to our family. We knew next to nothing about Ds and didn’t know what to expect – all we knew then was that our lives were going to be very different than what we had planned and envisioned.

It was between the shock, and I’ll admit the tears, of those initial few days that my husband Dan and I started thinking about research. What was going on the field of research to help us help assure our daughter would have the very best opportunities in life as possible?  We quickly learned about all of the community, educational, and advocacy resources that had made enormous strides in the past decade or two for people with Ds, and felt very fortunate to benefit from those tremendous efforts and successes……but what about research?

At the time, in 2003, if you went online to search Ds cognition research finding information was like finding a needle in a haystack. So after finding virtually nothing online, Dan and I began to network through Stanford, and Bill — I’m sure you don’t remember this, but I eventually tracked down your contact information and started hounding you (one might even say stalking you, but I will leave those details in the past).  But it was you who put me in touch with Patty who at the time was in the very beginning stages of founding this organization with Jim and the Kafkers in Boston.

So…that’s a long-winded way to tell you all how I got involved, but I tell it for two reasons.

The first is to paint the picture of how far this research has come in the last decade.  Today, in large part due to the work of those in this room, this same Google search results in pages and pages and pages of information and research breakthroughs. It was the goal of the honorees in this room to be a catalyst to cognition research, collaborate with the best and brightest and bring new researchers into the field – and they have done this in an incredibly short amount of time, and on an absolute shoestring budget.

The other reason I share the story is explain how innate and intuitive it was for Dan and I to know that cognition research was THE most important opportunity for our daughter.

When people ask me about my volunteer work and what LuMind is all about, I tell them it supports cognition research for people with Down syndrome. This usually results in blank stares, long pauses and a sense of confusion. Its’ not an easy thing to understand, like cancer research for example.  So I always try to describe it in more familiar terms, like glasses for someone who is visually impaired, or cochlear implants for someone who is hearing impaired.

We are not trying to change anyone — but just turn the dial and move the meter a bit on abilities. The ability to remember. How can you learn if you can’t remember? The ability and speed people with Ds process information. The ability to communicate, and ability to articulate thoughts and feelings.  It’s hard to put it into words, and in some ways you need to know someone with Ds well to understand it, but even small improvements in these areas will have a huge impact. The small improvements will impact the work they do at school, the richness of their friendships, the type of job they will have one day.  It will have a very direct impact on each child’s overall independence as adults, and even more importantly their risk of developing early onset Alzheimer’s disease.

Dan and I are convinced the research, whether results are subtle or significant, will have an enormous impact on Tate’s future. Yes, the years of weekly PT, OT, speech, socials skills therapy, and of course educational support we all give our kids is fundamental to their success, but cognition research, in my book has equal footing — and the potential to be a game changer to the futures of all those with Ds.

So it feels a little awkward to be here receiving an award for this work that is obviously very self-serving. It truly has been a labor of love.

And in case you were wondering, I thought I’d close by sharing that we were actually right in 2003 that our lives were going to be different. But what we didn’t know then, was what an overwhelmingly positive different it would be. Tate is the most fun, most loving and sincerely kind person we know. She is the nucleus of our family and it has been an absolute privilege to be her parents. Our goal, as with all of our kids, is for her to live her life to her greatest potential, and I thank all of you in this room for helping us do that.

The Sky’s the Limit for Down Syndrome Research!

Almost 100 people enjoyed the events during our “Sky’s the Limit” Awards weekend – a VIP reception, a research presentation by Dr. Harpold, Dr. Mobley, and Dr. Edgin, and of course, the inaugural Awards Gala on Saturday night.

Please enjoy our staff’s casual and candid photos of the Awards gala. We will have more photos and stories to share throughout the week. Thank you to everyone who participated, planned, or supported the event.

A special thank you to photographer Pavel Verbovski for capturing all the wonderful moments from the event. For those wishing to view and purchase professional images from the Gala, please visit the photographer’s website.

There’s still time to show your support with a donation in honor or one of our honorees – Dr. William Mobley, Dr. Jamie Edgin, Sarah Wernikoff, and Jim and Patty White. Select “Sky’s the Limit” when you make a donation and support our inaugural honorees.

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Recognizing the Pioneers in Down Syndrome Research – 2015 Awards Gala

We are so excited to be hosting our very first awards gala – The Sky’s the Limit – in Seattle on May 2, 2015.

We selected the Sky’s the Limit theme to represent the hope we feel. Thanks to your support over these 11 years, research that was once too complex to even consider is now experiencing tremendous breakthroughs. There are more discoveries, more exceptional, young researchers interested in pursuing careers in Down syndrome research, and interest from pharmaceutical firms to develop drug therapies.

Our inaugural event will honor five exceptional people who helped advance Down syndrome research. On Saturday evening, we will be presenting the following awards:

• Founders’ Award – Presented to Jim White and Patty O’Brien White on behalf of all those who were a part of the creation of the organization. This is a legacy award to be presented in 2016 and beyond to those who make an impact to the advancement of research.
• Dr. David Cox Rising Star Award – Presented to Dr. Jamie Edgin, University of Arizona
• Dr. William Cohen Researcher of Distinction Award – Presented to Dr. William Mobley, University of California, San Diego
• Luminary Award – Presented to Sarah Wernikoff, former Chairperson, LuMind Research Down Syndrome Foundation

About our Honorees:

Jamie Edgin, PhD, is an Assistant Professor in the Department of Psychology and the Sonoran UCEDD at the University of Arizona. Her research centers on studies of sleep and learning in Down syndrome, and she has been instrumental in devising new methods to measure cognition in those with Ds. Dr. Edgin serves on a number of community boards, including her service on the State of Arizona Developmental Disabilities Planning Council.

Dr. William Mobley, MD, PhD, is Distinguished Professor and Chair of the Department of Neurosciences at University of California, San Diego. He also serves as executive director of UCSD’s Down Syndrome Center for Research and Treatment. His research emphasis on the neurobiology of Down syndrome has brought new insights into Down syndrome, including possible therapies to improve cognition and unraveling the connections between Down syndrome and Alzheimer’s disease.

Sarah Wernikoff served as LuMind Board Chair from 2012-2014 and was a member of the LuMind board for 7 years. Her professional background includes over 15 years experience in ecommerce general business management, marketing strategy and planning, merchandising, and management consulting. Sarah has three children including an 11 year old daughter who has Down syndrome.

Jim White and Patty Ann O’Brien White are accepting this award on behalf of all of the people who were a part of the creation of the organization eleven years ago. Jim is a Managing Director with Sutter Hill Ventures and Patty is a marketing consultant at GSVlabs. The Whites have four children, including a daughter with Down syndrome.

If you would like to support the event, we are accepting donations in honor of the award recipients or for the event. Please learn more on our event page.

A big thank you to Confluence Health for their sponsorship of the Gala.

Q&A With Dr. William Mobley

Did 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.