Furthermore, since many of the agents currently in trials were developed based on information derived from the genetic mutations seen in the DIAN cohort, and since that information informed one of the major hypotheses (the amyloid hypothesis) about Alzheimer’s disease, it seems likely that these individuals are the most likely to respond to the treatments, he said, adding that if they are successful, these studies could bridge prevention trials between the genetic and sporadic forms of the disease.
Based on this rationale, DIAN is moving forward with the development of additional trials within the network, he said.
To date, a clinical trials committee has been formed and is charged with designing and managing the most effective trials through interactions with pharmaceutical sponsors, the National Institute on Aging, and the U.S. Food and Drug Administration. The committee has completed its scientific review and vetting of the rational for trials in this cohort, formed a "Pharma Consortium" with members from 12 pharmaceutical companies, and started the DIAN Therapeutic Trials Unit to implement the trials.
Multiple meetings have been held, and DIAN has obtained the support of regulatory agencies, including the FDA and the European Medicines Agency, Dr. Bateman noted.
Additionally, 11 therapeutic nomination packets have been received from pharmaceutical companies and are under consideration for use in the trials. He declined to identify the candidate drugs but said most are anti-amyloid agents.
The first trials should begin in early 2012, he said.
The hope is that these trials will lead to the same kind of success seen with statin drugs, which were initially tested in patients with an aggressive genetic form of hypercholesterolemia that struck people early in life, increasing their risk for heart attack and stroke.
The treatment was found to be effective in this population, and the findings translated into a highly effective therapy for the population at large, Dr. Bateman said, noting that millions of people around the world have benefited from treatment with those drugs.
The findings from DIAN, and the future directions of the network represent "a very exciting and new style of a collaborative type of multinational research, which is going to allow us to understand things in a way that couldn’t be done before by targeting populations at very high risk, and which allows us for the first time to really approach the problem of preventing Alzheimer’s rather than intervening after it’s developed, " said Dr. Ralph Nixon, professor of psychiatry and cell biology at New York University and moderator of a press briefing about the findings.
The approach is one that the Alzheimer’s Association has encouraged in recent years because "it cuts across a number of missions of the association, which are to underscore the importance of early detection so we can be in a position to treat these individuals when therapies are available for them," said Dr. Nixon, who also is vice chairman of the Alzheimer’s Association’s Medical and Scientific Advisory Council.
"But I think the most important message really is that we now have from this study the validation that it really is possible to detect changes at such an early stage that we are going to enhance the chances of administering therapies that will be more effective, even retesting therapies that might have failed in interventional trials ... as well as testing new innovative therapies that come along," he said.
DIAN is supported by a National Institutes of Health grant, as well as by grants from an anonymous foundation. The presenters had no conflicts of interest to report.