Alzheimer’s Drug Discovery Foundation Meeting Reports Advances


At the 19th International Conference on Alzheimer’s Drug Discovery, the focus was on gene therapy and alternative modalities for treating patients with neurodegenerative diseases, as well as the need for new biomarkers. 

In a keynote address, Rosa Canet-Aviles, Ph.D., Science Program Manager reviewed the effort to find biomarkers for Alzheimer’s disease (AD) for many purposes, which include identifying appropriate persons for clinical-trial participation and monitoring response to treatment. Following the keynote address, there were several presentations on potential blood tests that are in early development as biomarkers for AD. The goal of finding blood biomarkers is to facilitate diagnosis by lowering the cost of testing and making screening more efficient and easier for potential patients. 

Blaine Roberts, MD, of the Florey Institute of Neuroscience and Mental Health, and Tim West, PhD, of C2N Diagnostics, focused on the development of blood tests to measure amyloid beta (Aβ) levels. Efforts to isolate brain-derived exosomes as a potential biomarker were described by Diana Cha, PhD, of Brigham and Women’s Hospital. The ADDF is actively supporting the development of these tests through the Diagnostics Accelerator, an initiative advancing the search for blood and body-fluid novel biomarkers for AD. 

Imaging is another area of rapid progress in the search for AD biomarkers. Jacob Hooker, PhD, of Massachusetts General Hospital, described the use of a novel positron emission tomography (PET) ligand that can measure brain histone deacetylase (HDAC) levels to visualize how the brain transcriptome (messenger RNA levels) changes with normal aging and with AD. 

Gene therapy and stem cell approaches for AD were also presented. Anastasia Khvorova, PhD, of the University of Massachusetts Medical School, and her collaborator Evgeny Rogaev, are developing antisense oligonucleotides to reduce the expression of APOε4, a gene known to increase risk of AD. Ronald Crystal, MD of Weill Cornell Medicine, in contrast, is studying the effect of delivering APOε2, a protective allele, to the brain to counteract the effect of APOε4, and recently received approval to begin the first human clinical trial of APOε2 gene therapy. 

Other clinical trials presented and discussed included the safety and efficacy of nabilone, which significantly improved symptoms of agitation in a study of 39 patients with severe to moderate AD, presented by Krista Lanctôt, PhD of the Sunnybrook Research Institute, University of Toronto. Improvement in agitation with nabilone treatment occurred as quickly as 2 weeks and while some patients experienced sedation, 53% of patients tolerated the highest dose of 2 mg per day. A larger phase 3 study of nabilone is planned. Nabilone is a synthetic derivative of tetrohydrocannibinol marketed for nausea and vomiting associated with chemotherapy. 

Giacomo Koch, MD, PhD, of Santa Lucia Foundation, presented preliminary findings from the DOPAD trial (NCT03250741) of rotigotine in 94 patients with mild AD, in which patients experienced improvements in cognitive function and activities of daily living after 6 months of treatment. Rotigotine is a transdermal patch prescribed for Parkinson’s disease and restless leg syndrome. 

Efforts to refine acetylcholinergic treatments are also ongoing. Paul Newhouse, MD of Vanderbilt University Medical Center described a phase 1 study of a novel drug compound VU319 that modulates muscarinic acetylcholine receptor-1 (M1). Unlike previous drugs targeting M1, VU319 does not appear to have intolerable cholinergic side effects when tested at 5 different doses. A multiple-ascending dose study is planned to assess the safety and tolerability of consecutive 7-day dosing, and hopefully then there will be a phase 2a proof-of-concept double-blind placebo-controlled study to further assess safety and efficacy. 

“We have come a long way in our scientific understanding of Alzheimer’s disease, particularly in the past 10 to 15 years,” said Dr. Fillit. “This meeting highlights the support of ADDF, which has granted more than $115 million to fund more than 585 Alzheimer’s drug discovery programs and clinical trials in 18 countries.”

“This is a pivotal time in Alzheimer’s disease research and drug discovery,” said Dr. Howard Fillit, Founding Executive Director and Chief Science Officer of the ADDF. “Progress in many areas of research, including the identification of new biomarkers, novel drugs and gene therapy, as well as the use of existing drugs for other illnesses, show promise as new approaches for the prevention and treatment of Alzheimer’s disease.”


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