I recently watched a TED Talk on the subject of Alzheimer’s disease. This presentation, by Alanna Shaikh, starts with some very frightening statistics: “there's about 35 million people globally living with some kind of dementia, and by 2030 they're expecting that to double to 70 million.” She goes on to describe her father’s descent into dementia, her personal struggle with the possibility of inheriting the same disease and finishes with a hope that a cure will emerge in the near future. I highly recommend watching this very moving video.
Most of us will have a personal connection to Alzheimer’s in our lifetime and the wish for a cure is a sentiment echoed around the world. Earlier this month, the annual Alzheimer’s Association International Conference took place in Copenhagen (full program content can be found here: http://www.alz.org/aaic/portal/overview.asp). Of particular importance were five, very promising, drug trials that are being conducted over the coming years. A recent TIME magazine article perfectly summarized the participants and drugs being tested, so I won’t spend time doing the same. Instead I will attempt to provide a bit of clear background surrounding each one and what exactly it is that they trying to achieve.
1) Dominantly Inherited Alzheimer Network Trial (DIAN TU)
Research exists to suggest that significant changes occur in the brain long before any symptoms of Alzheimer’s are present, identifying these changes is important for both understanding the disease and also establishing how to halt its progress. DIAN TU aims to do this by examining individuals at risk for familial Alzheimer’s, this form is dominantly inherited and 50% of each generation will develop the disease (typically before the age of 60). Although slightly different to the more common form of late onset Alzheimer’s, studying this group provides a unique opportunity to evaluate sufferers before they begin displaying symptoms. Participants found to be negative for the mutated gene will be utilized in a control group and provided placebo medication. Those where the disease is likely to develop will be provided one of the two drugs being tested and biological markers of Alzheimer’s will be monitored (such as the development of brain plaques or changes in blood or cerebrospinal fluid). The goal of this trial is to slow or stop these disease indicators before the participants becomes symptomatic.
2) Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Study (A4)
The purpose of this study is to determine whether a new form of antibody investigational treatment is able to slow the memory loss caused by Alzheimer’s disease. In particular, the symptoms associated with the building of amyloid in the brain, which has been associated with changes in an individual’s mental state. These build-ups are able to remotely affect other parts of the brain, through affected communication between neurons, and are therefore highly damaging. Participants of this study all demonstrate increased plaques in the brain (but no outward symptoms of Alzheimer’s) and are therefore at risk of developing the disease in the future, without being current sufferers. This provides an opportunity for researchers to determine the effectiveness of this particular treatment in slowing memory loss before individuals begin suffering from the disease.
The aim of the TOMMORROW study is also to target Alzheimer’s at the root, or “silent stage”, before any significant cell injury has occurred. In order to do so, a strategy is needed to detect the people at risk, beyond the familial forms of the disease. In this case, work is being centered on the gene TOMM40. In conjunction with analysis of mutations on another gene, APoE, Alzheimer’s has previously been predicted in 97% of trial participants and the first part of the TOMMORROW study will be centered on confirming this research. With the gene markers identified, scientists will begin work on establishing the effectiveness of a diabetes drug (called pioglitazone) in the suppression of amyloid deposition in the brain (which as previously mentioned is linked to Alzheimer’s symptoms). If successful, individuals at risk would see a significant slowing in development of early disease symptoms.
4) Alzheimer’s Prevention Initiative Autosomal Dominant Alzheimer’s Disease Treatment Trial
As with DIAN TU, this trial will concentrate efforts on the familial strain of Alzheimer’s and work with participants who are cognitively normal but at high risk of developing the disease. Studying another anti‐amyloid antibody treatment, researchers plan to collaborate with those working on the very similar DIAN TU trial (albeit a different drug being tested). As with the others, the goal of this work is to attempt to slow the progression of symptoms before an individual starts displaying the biomarkers and symptoms of Alzheimer’s. Scientists working on another trial were able to display phase two results of administering of this drug, crenezumab, during the Copenhagen conference. Although they have been unable thus far to demonstrate any symptom reversal in those already experiencing cognitive decline, their work has provided further support to research attempting to halt the disease in early stages before any significant neurological change has occurred.
5) Alzheimer’s Prevention Initiative APOE4 Treatment Trial
Finally, the API trial will focus on individuals who have two copies of the previously mentioned ApoE4 allele, which has been associated with a high risk of Alzheimer’s development. The aim of this trial is to support the FDA approval of a successful drug and in recent weeks a partnership was announced. API will be working with Novartis to investigate two anti-amyloid drugs: an active immunotherapy and an oral medication, with aims to prevent or delay symptom onset in at-risk individuals. The immunotherapy is designed to get the body’s immune system to destroy amyloid proteins before they can cause harm, whilst the oral medication is designed to stop amyloid proteins being produced in the first place. Both drugs are designed to work in ways that differ from other anti-amyloid antibody therapies being tested elsewhere, particularly as they are being administered in some cases where very little existing amyloid build-up has been identified.