A new approach to treating Alzheimer’s disease uses a derivative of vitamin B1

With a $45 million grant from the National Institutes of Health and the National Institute on Aging, the Alzheimer’s Disease Cooperative Study (ADCS) at the University of California, San Diego, in collaboration with the Burke Neurological Institute (BNI) and Columbia University Irving Medical Center, will initiate a nationwide clinical trial to further investigate the therapeutic potential of benfotiamine, a synthetic version of thiamine (B1), as a metabolic treatment approach of Alzheimer’s disease.

The trial advances the ADCS’s mission to develop and test therapies to benefit people at risk of or exhibiting the symptoms of Alzheimer’s disease (AD). The ADCS will coordinate the multicenter trial to assess whether high doses of benfotiamine benefit people with mild AD or mild cognitive impairment due to AD (MCI).

The trial addresses tissue impairment of AD-related thiamine-regulated metabolic pathways. Previous work by co-lead researcher Gary E. Gibson, PhD, professor of neuroscience at the Brain and Mind Research Institute, part of Weill Cornell Medicine, found that a reduction in glucose metabolism is linked to this impairment of the processes thiamine dependent.

Using several experimental models, Gibson and others showed that increasing thiamine to very high levels using benfotiamine supplementation appeared to protect against Alzheimer’s-like symptoms. For the study, ADCS will enroll approximately 400 patients at up to 50 U.S.-based clinical trial sites, beginning in early 2023.

“We are delighted to receive this funding, which will expand testing of benfotiamine through to its clinical proof of concept, including adaptive testing for optimal dose and treatment response across clinical measures and biomarkers. “, said Howard Feldman, MD, dean of Alzheimer’s disease. Disease researcher and professor of neuroscience at UC San Diego School of Medicine.

The benfotiamine study will monitor participants for 18 months, using several measures, including cognitive tests and blood markers that signal the status and progression of AD and MCI.

“At the Burke Neurological Institute, we’ve been studying the effects of thiamine on neurodegenerative diseases for more than 40 years,” Gibson said. “This significant grant will allow us to test the treatment with hundreds of Alzheimer’s disease patients across the United States. We are eager to begin this crucial next stage of research.

“I am particularly excited about this trial because it will determine the relevance of these decades of research for the treatment of Alzheimer’s disease.

The essay highlights ADCS’ efforts to develop new interventional approaches. In collaboration with the University of Southern California, ADCS recently received a $50 million gift from the Epstein Family Foundation to support two programs: one investigating the use of gene therapy to treat Alzheimer’s disease and the other a “powder for pennies” (P4P) program designed to accelerate the testing of existing or repurposed drugs and natural products for its treatment.

Benfotiamine is a good example of the P4P approach. If beneficial, the treatment would be widely available and affordable.

Educational and lifestyle interventions are other approaches developed at ADCS. A study called HALT-AD, A Pilot for Healthy Actions and Lifestyles to Avoid Dementia or Hispanos y el ALTo a la Demencia, is a bilingual, bicultural program that recruits community members to join education programs and discussion groups, enabling them to learn more about dementia and practice preventive measures.

The recently completed EXERT study, nationally coordinated by ADCS, was a Phase III clinical trial to test whether exercise can slow the progression of mild memory loss and/or MCI in adults aged 65 to 89. The results of the study will be presented at the international conference of the Alzheimer’s Association in San Diego at the end of July.

“It’s crucial that ADCS helps lead the way in examining new possibilities for preventing and treating dementia,” Feldman said. “All indicators suggest that we can make progress by implementing a wide range of study methods.”

The benfotiamine study continues work funded by the Alzheimer’s Drug Discovery Foundation (ADDF).

“It is gratifying to see the research that the ADDF initially identified as promising and supported in a pilot study continue to be funded by the NIH National Institute on Aging,” said Howard Fillit, co-founder and chief scientific officer. of the ADDF. “With the improved biomarkers that have been developed since the pilot project, this next phase will lead to a better understanding of how benfotiamine works in the brain.”

Joining Feldman and Gibson as co-principal investigator in the new trial is José Luchsinger, MD, professor of medicine and epidemiology at Columbia University Irving Medical Center.

Other academic collaborators in the lab include the University of Gothenburg, Sweden; University of Cambridge, UK; and Georgetown University, Washington, DC Another study partner is C2N Diagnostics, a St. Louis company specializing in advanced brain health diagnostics.

More than 6 million Americans are currently living with Alzheimer’s disease, a figure that is expected to rise to nearly 13 million by 2050. Globally, the prevalence of Alzheimer’s disease is expected to rise from the current 57 million to 153 million in 2050. Currently, there is no cure for Alzheimer’s disease. A D.

About the Alzheimer’s Disease Cooperative Study
The Alzheimer’s Disease Cooperative Study (ADCS) is an academic research organization located at UC San Diego dedicated to developing treatments for those at risk for or affected by Alzheimer’s disease. For more than 30 years, with funding such as the National Institute of Aging, he has been a leader in the development of potential new treatments through innovation in clinical trials with the design, methods and to analyse. It has a trial coordination center in San Diego and a network of participating sites across the United States.

About the Alzheimer’s Drug Discovery Foundation
Founded in 1998 by Leonard A. and Ronald S. Lauder, the Alzheimer’s Drug Discovery Foundation (ADDF) is dedicated to rapidly accelerating drug discovery to prevent, treat and cure Alzheimer’s disease. The ADDF is the only public charity focused exclusively on funding drug development for Alzheimer’s disease, employing a venture philanthropy model to support research in universities and the biotech industry. Through the generosity of its donors, the ADDF has awarded more than $209 million to fund more than 690 Alzheimer’s disease drug discovery programs, biomarker programs and clinical trials in 19 countries. To learn more, please visit the ADDF website.

About the Burke Neurological Institute
The Burke Neurological Institute is based in White Plains, NY, and was established in 1978 by Dr. Fletcher McDowell as a research institute dedicated to finding cures for chronic neurological disorders. The Institute turns groundbreaking research into clinical treatments so people can see, talk and walk again. Their goal is to combine the most rigorous contemporary brain science with sincere compassionate care to innovate and develop new remedies for stable disability in people with neurological conditions such as stroke, traumatic brain injury or spinal cord injury. Burke Neurological Institute is an academic affiliate of Weill Cornell Medicine.