Category Archives: Ds Research News

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

AC Immune

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 SupraAntigenTM 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

 

 

 

Might Normalizing Brain Development Help in Down’s Syndrome?

LuMind Research Down Syndrome Foundation’s Chief Scientific Officer Dr. Michael Harpold was referenced in a discussion from the Society for Neuroscience Annual Meeting. The article discusses if the cognitive impairments associated with Down syndrome could be prevented.

Dr. Harpold was mentioned along with others from Tufts Medical in Boston, Univeristy of Bologna in Italy and Institute for Basic Research’s Genetics Laboratory.

Check out the full article.

 

 

 

What’s happening in Down syndrome research?

How do you keep up with the latest in Down syndrome research?

NewspaperWe know you love Dr. Harpold and all the LuMind RDS-funded researchers who let you know about the advances in cognition research, but there’s a big world of discoveries out there.

We’ve curated the latest scientifically-credible articles for you on our website. We’ll be keeping this page current, so please send us any articles that interest you. We want to be sure we – and you – see it all!

Check it out: LuMind RDS: Down Syndrome Research News.

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.

 

 

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.

Dr. Harpold Quoted in Education Week Articles on Down Syndrome Research

Education Week HeaderEducation WeekLuMind Foundation’s Chief Scientific Officer, Dr. Michael Harpold, was quoted in an article by Education Week on the NIH Down Syndrome Research report.

In the article, titled “NIH Resets Study Plans for Down Syndrome,” author Sarah Sparks summarizes the seven-year research plan, including discussing a greater focus on students in educational settings.

Dr. Harpold is quoted on the report illustrating an emphasis on improving cognition and the interrelationships between educational approaches and research areas. He also acknowledges that funding for research endeavors is a critical factor in progressing research.

Read more comments by Dr. Harpold on NIH’s research plan and read the entire Education Week article here.

Dr. Harpold was also quoted in another article, also on Education Week, discussing DS-Connect, the Down syndrome registry. Read that article here.

 

 

 

Update on Transition Clinical Trial: ELND005

Transition Therapeutics Inc. (Elan) announced the results of a clinical study of drug candidate ELND005 in young adults with Down syndrome. The study focuses on neuropsychiatric symptoms associated with Alzheimer’s disease and cognition in people with Ds.

In our September 2013 Newsflash, LuMind Foundation’s Chief Scientific Officer Dr. Harpold explained the ELND005 study. Essentially, ELND005 is a molecule that may hold the potential to improve cognition in Ds, in part, by reducing aggregation of beta-amyloid, which is a product of the amyloid precursor protein (APP) encoded by a gene on chromosome 21 — thus preventing the intraneuronal buildup of beta-amyloid plaques that most people with Ds develop by their 40s associated with Alzheimer’s disease.

LuMind-supported research has previously shown reducing the levels of APP and/or certain of the APP-derived beta-amyloid products overcome specific cognitive and neurodegenerative Alzheimer’s disease-related effects in mouse models of Down syndrome.

LuMind has also been working with Transition Therapeutics to supported clinical trial participant recruitment. Your donations and support helped advance this clinical trial!