Amyloid PET Scan Can Predict Progression to Alzheimer’s in Patients With Mild Cognitive Impairment

MedicalResearch.com Interview with:

David A. Wolk, MD Associate Professor Department of Neurology Co-Director, Penn Memory Center Associate Director, Alzheimer’s Disease Core Center University of Pennsylvania

Dr. Wolk

David A. Wolk, MD
Associate Professor
Department of Neurology
Co-Director, Penn Memory Center
Associate Director, Alzheimer’s Disease Core Center
University of Pennsylvania

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Mild Cognitive Impairment (MCI) is a state when individuals have mild memory problems, but not enough to impact day-to-day function.  Many patients with MCI are on the trajectory to developing Alzheimer’s Disease dementia, but about half will not and remain stable.  As such, patients with MCI are often uncertain about the likelihood they should expect to decline in the future which obviously may be associated with considerable anxiety and this may delay opportunities for them to plan for the future or begin therapeutic interventions.

This study examined the degree to which amyloid PET, which detects the amyloid pathology of Alzheimer’s Disease, a measure of shrinkage of the hippocampus with MRI, and cognitive measures predicted development of dementia over 3 years.  We found that each of these measures enhances prediction of whether an individual will or will not develop dementia in the future.  If all of these measures are positive, one has a very high risk of progression whereas if amyloid PET and the MRI measurement are normal, there is very little risk of progression. Continue reading

Sleep Deprivation Leads to Build Up of Junk Amyloid in Brain

MedicalResearch.com Interview with:

Nora D. Volkow MD Senior Investigator Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health, Bethesda, MD 20892

Dr. Nora Volkow

Nora D. Volkow MD
Senior Investigator
Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health, Bethesda, MD 20892

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Findings from animal studies had shown that sleep deprivation increased the content of beta-amyloid in brain, which is a risk factor for Alzheimer’s disease.  We wanted to test whether this also happened in the human brain after one night of sleep deprivation. We found that indeed one night of sleep deprivation led to an accumulation of beta amyloid in the human brain, which suggest that one of the reasons why we sleep is to help clean our brain of degradation products that if not removed are toxic to brain cells.  Continue reading

Genetic Overlap Between Some Types of ALS and and Dementia

MedicalResearch.com Interview with:

Celeste Karch, PhD Assistant Professor of Psychiatry Molecular mechanisms underlying tauopathies Washington University School of Medicine St Louis

Dr. Karch

Celeste Karch, PhD
Assistant Professor of Psychiatry
Molecular mechanisms underlying tauopathies
Washington University School of Medicine
St Louis

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Nearly half of all patients with amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disorder, develop cognitive problems that affect memory and thinking. Why a disease that primarily affects movement also disrupts thinking has been unclear.

Our findings suggest that genetic connections between the two disorders may explain why they share some of the same features and suggest that some drugs developed to treat ALS also may work against frontotemporal dementia and vice versa. We used a statistical method in almost 125,000 individuals with ALS, frontotemporal dementia (FTD), progressive supranuclear palsy, corticobasal degeneration, Alzheimer’s disease and Parkinson’s disease to determine whether there are common genetic variants that increase risk for multiple neurodegenerative diseases.

We found that common variants near the MAPT gene, which makes the tau protein, increases risk for ALS. MAPT has previously had been associated with diseases including frontotemporal dementia and Alzheimer’s disease. But the gene hadn’t been linked to ALS. We also identified variations in a second gene, BNIP1, which normally plays an important role in protecting against cell death, increased the risk of both ALS and frontotemporal dementia. ImportantlyBNIP1 mRNA levels were altered in people who had ALS and in patients with frontotemporal dementia, suggesting the BNIP1 may be a potential therapeutic target for both disorders.

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LMTX® Shows Promise As Monotherapy In Mild Alzheimer’s Disease

MedicalResearch.com Interview with:

Professor Claude Wischik Co-Founder and Executive Chairman TauRx Pharmaceuticals

Prof. Wischik

Professor Claude Wischik
Co-Founder and Executive Chairman
TauRx Pharmaceuticals

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The study TRx-237-005 was the second of two Phase 3 trials conducted by TauRx, and was specifically set up to investigate the efficacy and safety of LMTX® in 800 patients with mild Alzheimer’s disease at a dose of 100 mg twice daily compared to 4 mg twice daily (intended as an inactive control dose) over an 18-month treatment period.

Results from this study were found to be consistent with those from the first Phase 3 study in mild to moderate Alzheimer’s disease, published in The Lancet [(TRx-237-015) Gauthier et al. 2016], indicating that patients obtained no benefit from LMTX® when it was taken in combination with existing approved drugs for Alzheimer’s disease and supporting the hypothesis that LMTX® might be effective as monotherapy at doses as low as 4 mg twice daily. Please refer to the press release for full study results.

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Single Injection of Klotho Gene Protected Animals From Cognitive Decline

MedicalResearch.com Interview with:

Dr Miguel Chillon PhD Department of Biochemistry and Molecular Biology Universitat Autonoma Barcelona Spain

Dr. Chillon

Dr Miguel Chillon PhD
Department of Biochemistry and Molecular Biology
Universitat Autonoma Barcelona
Spain

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Klotho is a protein with an anti-aging and neuroprotective role. Recent studies show it prevents the development of cognitive problems associated with aging and Alzheimer’s disease. Klotho works mainly by inhibiting the insulin / IGF-1 signaling pathway and decreasing the damage caused by oxidative stress in the brain. One of the latest results revealed that the concentration of Klotho in cerebrospinal fluid is significantly lower in Alzheimer’s patients than in human controls of the same age; and it is lower in the elderly with respect to young adults.

Our study used a gene therapy strategy to introduce the Klotho gene into the Central Nervous System of adult animals. With just a single injection of the Klotho gene, young adult animals were protected over time from the cognitive decline associated with aging in old animals. These exciting results pave the way to further advances in research and the development of a neuroprotective therapy based on Klotho.

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Refined Biomarker Model Can Guage Risk of Alzheimer’s In Patients With Mild Cognitive Impairment

MedicalResearch.com Interview with:
Ingrid S. van Maurik, MSc
Department of Neurology and Alzheimer Center
Department of Epidemiology and Biostatistics
Amsterdam Neuroscience
VU University Medical Center
Amsterdam, the Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: CSF and MRI biomarkers are increasingly used in clinical practice, but their diagnostic and prognostic value is not perfect. Furthermore, criteria do not specify how to deal with conflicting or borderline results, or how to take patient characteristics into account. Therefore, optimal use of these biomarkers in clinical practice remains challenging.

As part of the ABIDE project, we constructed biomarker-based prognostic models (CSF, MRI and combined) that enable prediction of future Alzheimer’s disease, or any type of dementia, in individual patients with mild cognitive impairment. When using these models, any value can be entered for the variables, resulting in personalized probabilities with confidence intervals.

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Alzheimer’s Disease: Tramiprosate Envelopes Amyloid Protein To Prevent Misfolding Into Aggregates

MedicalResearch.com Interview with:

Dr. Petr Kocis Vice President Preclinical Development Alzheon, Inc. University of Oxford

Dr. Kocis

Dr. Petr Kocis PhD
Vice President Preclinical Development
Alzheon, Inc.
University of Oxford

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Researchers widely accept that amyloid plaques are the hallmark of Alzheimer’s disease. However, for many years, drug development has focused on the solid amyloid plaque as a primary disease culprit. Recent advances show that it is more likely that early stage soluble beta amyloid oligomers play a key role in the pathogenic process of Alzheimer’s disease.

A paper recently published by Alzheon, a company developing medicines for Alzheimer’s disease and other neurological disorders, suggests a new therapeutic mechanism for targeting toxic amyloid beta oligomers with a small molecule, tramiprosate, the active agent in the drug candidate, ALZ-801. ALZ-801 is a Phase 3-ready drug candidate that is an optimized prodrug of tramiprosate, with a substantially improved pharmacokinetic and safety profile compared to tramiprosate.

Alzheon scientists discovered that tramiprosate acts to inhibit the production of neurotoxic beta amyloid oligomers by ‘enveloping’ the amyloid peptide to prevent its misfolding into soluble amyloid aggregates. Beta amyloid oligomers are believed to be key drivers of the pathogenic process in Alzheimer’s disease (AD). This novel enveloping mechanism of tramiprosate prevents the self-assembly of misfolded proteins into beta amyloid oligomers that lead to amyloid aggregation and, subsequently, cause neuronal toxicity and clinical progression in Alzheimer’s disease. These results were published in the medical journal, CNS Drugs, and the paper is available through Open Access here. [“Elucidating the Aß42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer’s Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data”]

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Nasal Spray of Stem Cell Vesicles First Step Toward Treating Brain Diseases

MedicalResearch.com Interview with:

Dr. Darwin J. Prockop, M.D., Ph.D. Professor and Director Institute for Regenerative Medicine Texas A&M Health Science Center College of Medicine Temple, TX

Dr. Prockop

Dr. Darwin J. Prockop, M.D., Ph.D.
Professor and Director
Institute for Regenerative Medicine
Texas A&M Health Science Center College of Medicine
Temple, TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We and many others have been trying for many years to develop therapies with adult stem cells that might rescue the brain from the injuries and disease. Recently many of found that small vesicles secreted by adult stem cells have many of the beneficial effects of the cells themselves. The paper shows that a nasal spray of the vesicles can rescue mice from the long-term effects of severe epilepsy.

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Mechanical Ventilation Doubles For Persons With Advanced Dementia

MedicalResearch.com Interview with:

Joan M. Teno, MD, MS Department of Gerontology and Geriatrics, Cambia Palliative Care Center of Excellence University of Washington Medicine Seattle, Washington

Dr. Joan Teno

Joan M. Teno, MD, MS
Department of Gerontology and Geriatrics,
Cambia Palliative Care Center of Excellence
University of Washington Medicine
Seattle, Washington

MedicalResearch.com: What is the background for this study?

Response: An important challenge for our health care system is effectively caring for persons that high-need, high-cost — persons afflicted with advanced dementia and severe functional impairment are among these persons, with substantial need and if hospitalized in the ICU and mechanically ventilated are high cost patients, who are unlikely to benefit from this level of care and our best evidence suggest the vast majority of persons would not want this care. In a previous study, we interviewed families of advance dementia with 96% starting the goals of care are to focus comfort. Mechanical ventilation in some cases may be life saving, but in cases such as those with advanced dementia and severe functional impairment, they may result in suffering without an improvement in survival.

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Experimental Antibody Reduced Amyloid Plaques in Alzheimer’s

MedicalResearch.com Interview with:

Roger M. Nitsch, MD Professor and Director Institute for Regenerative Medicine · IREM University of Zurich Campus Schlieren Switzerland

Prof. Roger Nitsch

Roger M. Nitsch, MD
Professor and Director
Institute for Regenerative Medicine · IREM
University of Zurich Campus Schlieren
Switzerland

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The main finding is that treatment with aducanumab resulted in an unprecedented reduction of brain amyloid plaques in patients with Alzheimer’s disease.  The removal of amyloid from patients brains were both dose- and time-dependent.  We also observed initial hints for stabilized brain functions in patients receiving aducanumab.  In contrast, patients in the placebo group continued to declined as usual in this stage of Alzheimer’s disease.

The main safety finding in 22% of all treated patients was ARIA – an Amyloid-Related Imaging Abnormality – suggestive of fluid shifts in the brains. In most cases, ARIA occurred in the absence of clinical signs and resolved spontaneously.  In one third of the ARIA cases, patients experienced transient headaches.  None of the patients had to hospitalized because of ARIA.

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