In what has been hailed "a significant event in the history of Alzheimer's and dementia research," scientists have completed the first ever phase III clinical trial of a drug that targets one of the drivers of Alzheimer's disease - a protein known as tau.
Tau is considered a hallmark of Alzheimer's disease; the protein can form twisted fibers in the brain called "tangles," which are believed to cause nerve cell death.
In a study recently presented at the Alzheimer's Association International Conference 2016 (AAIC 2016), held in Toronto, Canada, researchers reveal how a drug called LMTX shows promise for halting the formation of tau tangles.
Alzheimer's disease is estimated to affect 5.4 million people in the United States, and by 2050, it is expected to affect around 13.8 million Americans, unless new treatments are identified that tackle the disease at its roots.
For years, scientists have worked to find ways to combat the two prime suspects for Alzheimer's development: tau tangles and amyloid plaques - clumps of beta-amyloid protein, which are believed to disrupt nerve cell communication.
Medical News Today have reported on some interesting developments in this field; a study earlier this month, for example, revealed the creation of a vaccine that researchers say could halt the formation of tangles and plaques.
While an undoubtedly exciting development, it will still be another 3-5 years before this vaccine can be tested in humans, and this long road to human trials been the case for the vast majority of Alzheimer's studies - until now.
Dr. Serge Gauthier - of the Departments of Neurology & Neurosurgery, Psychiatry, and Medicine at McGill University in Canada - and colleagues have completed the first ever phase III trial of a drug that targets the tau protein, and the drug in question - LMTX - proved beneficial for a small subgroup of patients.
LMTX found beneficial for patients not using other Alzheimer's treatments
According to the researchers, LMTX - developed by TauRx Pharmaceuticals - is a tau aggregation inhibitor (TAI), meaning it targets the tau protein in the brain and prevents it from forming tangles that contribute to Alzheimer's disease.
For their phase III trial, Dr. Gauthier and colleagues enrolled 891 patients of an average age of 70.6 years who had mild or moderate Alzheimer's disease. Subjects were recruited from 115 sites over 16 countries across Asia, Europe, North America, and Russia.
Participants were randomized to receive one of three treatments for 15 months: oral LMTX at a dose of 150 milligrams daily, oral LMTX at a dose of 250 milligrams daily, or a control dose of 8 milligrams of LMTX daily - the placebo - in order to maintain blinding to treatment.
Around 85 percent of subjects were also using other forms of approved treatment for Alzheimer's, the team reports.
At study baseline and every 13 weeks thereafter, subjects underwent brain imaging and standard tests of cognitive functioning and day-to-day functioning, including the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL).
Results of LMTX efficacy and safety were assessed as a whole and by disease severity, region, and the use of other Alzheimer's treatments.
Across the full study population, LMTX at both doses was found to have no benefit for cognitive functioning, daily functioning, or brain atrophy - the loss of nerve cells - compared with the placebo.
However, the team found that patients who were not using any other approved Alzheimer's treatment - that is, they only used LMTX - showed improvements in cognitive and daily function, as well as reduced brain atrophy. These effects were found for both doses of LMTX.
At least one adverse event was reported by more than 80 percent of participants. Gastrointestinal problems, nervous system disorders, infections and infestations, and renal and urinary disorders were the most commonly reported conditions.
Team 'excited' by the findings
While the study only demonstrated the benefits of LMTX for a small number of Alzheimer's patients, the researchers are encouraged by the findings.
"In a study of this size across a combined mild to moderate patient population, it is both encouraging to see improvements of this magnitude in the standard cognitive and functional tests and reassuring to see the supporting brain scan evidence of a slowing in disease progression during 15 months of treatment," says Dr. Gauthier.
"As a practicing clinician I see Alzheimer's patients, their families and caregivers every day, and continually share their desperate need for a truly therapeutic product as today we only have symptomatic treatments available to us.
In a field that has been plagued by consistent failures of novel drug candidates in late-stage clinical trials and where there has been no practical therapeutic advance for over a decade, I am excited about the promise of LMTX as a potential new treatment option for these patients."
Dr. Serge Gauthier
While the results clearly hold promise for a much-needed treatment that targets Alzheimer's at its core, the researchers stress that more studies are required to determine why LMTX does not appear to work in combination with other therapies.
"The results we see in those patients not taking Alzheimer's disease medications show the considerable potential of LMTX as a monotherapy for both mild and moderate Alzheimer's disease," says Prof. Claude Wischik, of Aberdeen University, United Kingdom, and co-founder of TauRx.
"However, the reason for the observed loss of efficacy of LMTX when taken in combination with currently available treatments for Alzheimer's disease is not as yet understood."