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AAIC 2016: Highlights In Prevention, Detection And Treatment Of Alzheimer’s Disease

AAIC 2016: Highlights In Prevention, Detection And Treatment Of Alzheimer’s Disease

Over a century since the first case of Alzheimer’s disease was described, researchers, physicians and caregivers have made tremendous strides toward improving patient outcomes for those with the neurodegenerative disorder. Those in the industry have, however, faced challenges in understanding the underlying mechanisms responsible for Alzheimer’s pathology, and in developing new therapies for the condition. The US Food and Drug Administration (FDA) has, in fact, not approved a new Alzheimer’s treatment in the past 12 years.

The prevalence of Alzheimer’s in the US today is estimated to be about one in nine in individuals 65 years and older. As the sixth leading cause of death in the US, this form of dementia is expected to affect 13.8 million people by 2050, if no new preventative or curative medicines are developed in the next 34 years.

The Alzheimer’s Association is the nation’s leading organization devoted to supporting Alzheimer’s research and care for those with dementia. Xtalks attended this year’s Alzheimer’s Association International Conference (AAIC), to get an idea of what advances have been made in Alzheimer’s research, and which companies are helping to support those efforts.

Non-Pharmacological Prevention Of Alzheimer’s Disease

A study conducted by researchers at the Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health, found an interesting association between occupational complexity and pathologies associated with Alzheimer’s disease. The researchers – including conference presenter Elizabeth Boots, a research specialist at the Wisconsin Alzheimer’s Disease Research Center – studied the brains of 284 late-middle-aged healthy individuals who were at risk of developing Alzheimer’s.

The research focused on white matter hyperintensities (WMHs), a key indicator of cerebrovascular disease, which can be identified on brain scans as white spots. These WMHs have been associated with Alzheimer’s disease and an increased risk of cognitive decline in older individuals.

By comparing WMH data with each participant’s cognitive abilities and their occupational complexity, Boots and her colleagues found that working with people contributed most to cognitive reserve. Despite having higher numbers of WMHs than their peers, those with higher occupational complexity maintained their level of cognitive function.

“These findings indicate that participants with higher occupational complexity are able to withstand pathology associated with Alzheimer’s and cerebrovascular disease and perform at a similar cognitive level as their peers. This association is primarily driven by work with people, rather than data or things,” said Boots. “These analyses underscore the importance of social engagement in the work setting for building resilience to Alzheimer’s disease.”

Smell-Based Biomarkers Of Alzheimer’s Disease

Alzheimer’s disease is currently only able to be diagnosed in later stages using positron emission tomography (PET) imaging of beta amyloid plaques in the brain, or using a lumbar puncture to detect the protein in the cerebrospinal fluid (CSF). While both techniques are useful, they can be expensive, laborious for the clinician and sometimes painful for the patient.

In order to identify biomarkers that could facilitate earlier Alzheimer’s diagnosis, without the drawbacks of other methods, researchers at Columbia University Medical Center used the University of Pennsylvania Smell Identification Test (UPSIT) to assess the odor identification abilities of those with memory decline. Considered to be the “gold standard” of smell identification tests, the UPSIT uses 40 “scratch and sniff” strips and a multiple choice testing format to assess a person’s olfactory functioning.

Using PET or CSF analysis through lumbar puncture, the researchers assessed the level of beta amyloid in 58 patients with amnesic mild cognitive impairment and 26 healthy controls, all with a mean age of 68. These same patients were also asked to perform the UPSIT, and their level of absolute smell function was compared to a database of normal individuals.

Sixty-seven percent of study participants showed memory decline at the six month follow-up mark, and measures of beta amyloid were found to predict this decline. While the UPSIT score was not identified to be a strong predictor of memory decline in this study, the researchers did find that participants with a score of less than 35 were nearly four times as likely to experience memory decline, compared to those with a higher score.

“Our research suggests that both UPSIT score and amyloid status predict memory decline,” said Dr. William Kreisl, research presenter from Columbia University Medical Center. “Younger age, higher education, and shorter follow-up may explain why UPSIT did not predict decline as strongly in this study as in previous studies. While more research is needed, because the UPSIT is much less expensive and easier to administer than PET imaging or lumbar puncture, odor identification testing may prove to be a useful tool in helping physicians counsel patients who are concerned about their risk of memory loss.”

Phase III Clinical Trial Results Of Tau Inhibitor

Of all the oral sessions this year at the AAIC, an afternoon session nearing the end of the conference was likely the best-attended presentation. Every seat in the small meeting room was filled, with attendees spilling out into the back of the lecture hall and even out the door.

So what was the big attraction? Speakers in this session released the results of the first ever Phase III clinical trial of a drug targeting tau protein in patients with Alzheimer’s disease.

Tau proteins play an important role in Alzheimer’s pathology, as they form potentially-cytotoxic tangles in the neurons of those with the degenerative disease. Developed by TauRx Therapeutics, the focus of the clinical trial – the drug leuco-methylthioninium-bis (hydromethanesulfonate) (LMTM) – has previously been shown to inhibit tau aggregation in both in vitro conditions, and in mouse models of the disease.

The multisite study included 891 patients with probable Alzheimer’s from 16 countries, including those in North America, Europe and Asia. Participants were randomly assigned to receive a high dose, low dose or control dose of the experimental treatment.

At the end of the 15-month clinical trial, the study investigators found that treatment with LMTM, at either dose, was not associated with better outcomes compared to the control arm. However, in a preplanned analysis of patients taking the drug as a monotherapy – or those who were not taking any Alzheimer’s medications at the start of the trial – the drug showed a statistically significant improvement on cognitive outcomes in the patients.

While the subgroup analysis is encouraging, it’s difficult to say whether the drug will be pushed into additional Phase III trials.* What’s more, over 80 percent of patients in the clinical trial experienced adverse events, including gastrointestinal disorders, infections, infestations and nervous system disorders.

“The study results failed to demonstrate a treatment benefit on either of the co- primary outcomes at either dose in the prespecified primary analysis,” said Dr. Serge Gauthier, Professor in the Departments of Neurology and Neurosurgery, Psychiatry, Medicine, at McGill University, and the presenter at the conference. “However, additional analyses are very encouraging and showed that patients taking LMTM as monotherapy had significantly lower decline than control patients or those taking LMTM as an add-on to existing Alzheimer’s treatments.”

Industry Viewpoint

Advances in the way Alzheimer’s patients are diagnosed, cared for and treated would not be possible without industry partners. I had a chance to speak to a number of representatives from some leading-edge companies while visiting the Exhibit Hall at the AAIC. Here’s what they had to say about their contribution to Alzheimer’s disease and what the future holds for individuals diagnosed with, or at risk of developing, the debilitating neurodegenerative disorder.

Gary Gregory, President of Neuronix: “Neuronix is excited to launch our non-pharmaceutical, non-invasive treatment for Alzheimer’s disease at a rapidly growing number of sites across the UK and Europe. We have been pleased by the positive reaction from physicians, patients and families and look forward to helping consultants treat patients in their fight against this devastating disease.”

Violeta Jordan, Global Director of Research Product Management at Bachem Americas, Inc.: “Our main discussion in the Exhibition Hall is always on how can all of us, including vendors and customers, help to advance Alzheimer’s research? Bachem’s contribution is by offering catalog portfolio of over 200 Amyloid related peptides in stock, our new Tau peptides and peptides labeled with Tide Fluor™ dyes & Tide Quencher™ acceptors. We are looking forward to the next AAIC 2017 meeting in London.”

Dr. Peggy Taylor, General Manager, Neuroscience at BioLegend: “There’s been quite a bit of talk at this conference about the crossover in neurodegenerative disease, such that some of the pathologies that used to be considered Alzheimer’s disease pathologies, are also present in Parkinson’s disease and other neurodegenerative diseases. I think that some of the issues with the earliest drugs is that they were looking in the patient population after diagnosis. Some of the things that have been evaluated now are [focused] more on the pathways rather than the pathological hallmarks. I think that the interventions at those [earlier] points may prove quite fruitful.”

Outlook On Alzheimer’s Disease

While many at this year’s AAIC were optimistic about a not-too-distant future where Alzheimer’s disease will be better managed, treated or even prevented altogether, some felt that we still have a long way to go before we can reach these goals. Historically, experimental Alzheimer’s drugs have had abysmal failure rates in clinical trials – a fact that leads many pharmaceutical companies to be wary of investing too heavily in the space. This lack of investment means Alzheimer’s research is years behind that of more well-funded areas including oncology and cardiovascular disease.

For now, the most successful efforts seem to be in the caregiver sector, where new tools and methods are being developed to help optimize the quality of life for patients with Alzheimer’s disease. Cognitive and memory-based training programs also show great promise in slowing the progression of the disease, potentially improving the capacity of these patients to live longer, more autonomous lives, in spite of their Alzheimer’s diagnosis.

Be sure to check out next week’s blog article for more in-depth interviews with companies dedicated to advancing Alzheimer’s disease research.

*Correction made on on August 5, 2016: Phase of clinical trials changed from IV to III.

Did you attend this year’s AAIC 2016? What is your outlook on the field of Alzheimer’s disease research in prevention, early diagnosis, and treatment options? Share your views in the comments section below!