The University of New Mexico Health Sciences is taking a significant step towards developing a vaccine against Alzheimer’s disease. Researchers have successfully conducted experiments in mice and non-human primates, demonstrating the efficacy of an experimental vaccine that targets the tau protein associated with the disease. The team, led by Kiran Bhaskar, PhD, has published their findings in a recent paper, which sheds light on the potential breakthrough in this field.

Tau is a naturally occurring protein that helps stabilize neurons, but when it undergoes a process called phosphorylation, it deforms and is ejected from neurons into the extracellular space, creating tangles characteristic of Alzheimer’s and other neurodegenerative diseases. The vaccine developed at UNM generates antibodies that bind to pT181, a region of the altered tau protein identified as an Alzheimer’s biomarker.

In their paper, Bhaskar and his team reported that when the vaccine was administered to mice bred to express pathological tau, they generated antibodies, reduced the extent of tangles in key brain structures, and improved their performance on cognitive tests. The researchers also found that the vaccine elicited a strong immune response in two other strains of mice and even in macaques, primates whose immune systems and brains are closer to humans.

This promising development has led Bhaskar to believe that the vaccine is now close enough to human clinical trials. “Because we’ve shown efficacy in the non-human primate, I think that is suggesting to us it’s much closer to a clinical trial,” he said.

The team is seeking funding from venture capitalists and the Alzheimer’s Association to launch a Phase 1 trial in humans. While there are several FDA-approved treatments for Alzheimer’s, they have only a modest effect on the progression of the disease. Targeting tau might be a better bet, as it could potentially address the root cause of the disease.

The vaccine was developed using a virus-like particle (VLP) platform, which has been shown to create durable immunity with just one primary inoculation and two booster shots. VLP-based vaccines have been proven safe in humans and don’t require adjuvants, making them an attractive option for this type of treatment.

Nicole Maphis, PhD, a postdoctoral researcher at UNM, was the first author on both vaccine papers. She emphasized the importance of collaborating with UC Davis to validate the vaccine’s efficacy, saying, “This was important because it extends our work in an animal model that is more similar to humans.”

As researchers continue to explore this promising avenue for treating Alzheimer’s, the hope for a breakthrough grows. With the potential for a vaccine that targets the tau protein, patients and families affected by the disease may finally have a chance at a better future.

The most critical complication to watch out for after receiving a lung transplant is Chronic Lung Allograft Dysfunction (CLAD). Once CLAD develops, there are no universally effective treatments available. Therefore, preventing this complication takes top priority for those who have undergone a lung transplant. One of the primary immunosuppressing medications used in lung transplant recipients is calcineurin inhibitors.

There are only two calcineurin inhibitors: cyclosporine and tacrolimus. Each has different formulations, such as once-daily slow-release tacrolimus, twice-daily immediate-release tacrolimus, and twice-daily cyclosporine. While these medications share the same goal of preventing rejection, it is unclear whether they are equally effective. CLAD encompasses a range of clinical manifestations that ultimately lead to the transplanted lung losing its normal function.

The presentation of CLAD can vary among patients, with some experiencing an obstructive ventilatory defect, others having a restrictive defect, and some exhibiting a combination of both. Unfortunately, once CLAD develops, lung function does not improve. In the absence of effective treatments, strategies to prevent CLAD are crucial.

A recent study published in the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry data found a significant survival benefit between using tacrolimus versus cyclosporine after lung transplantation. Out of 22,222 individuals with data on chronic lung allograft dysfunction treatment, 88.6% received immediate-release tacrolimus. The participants taking immediate-release tacrolimus had a much lower rate of experiencing CLAD than those who took twice-daily cyclosporine.

Michael Combs, an assistant professor of pulmonary diseases and internal medicine at Michigan Medicine, led the research team conducting this study. Combs highlighted the positive findings for twice-daily immediate-release tacrolimus in this study, stating that it should reassure transplant patients and providers that using this formulation is the superior treatment to cyclosporine.

“This present study should reassure transplant patients and providers twice-daily tacrolimus — and not only once-daily tacrolimus — is the superior treatment to cyclosporine,” said Combs. “Importantly, in our study we found that twice-daily tacrolimus not only resulted in lower rates of CLAD relative to cyclosporine, but it was also associated with improved overall survival after lung transplantation. This is an important, patient-centered finding which has not been previously demonstrated.”

In conclusion, the most effective prevention method for complications post-lung transplant is using tacrolimus, regardless of its formulation. This treatment offers a significant advantage over cyclosporine in preventing CLAD and improving overall survival after lung transplantation. Future research will need to investigate whether once-daily medication regimens are superior to twice-daily formulations.

The study published in the American Journal of Human Genetics reveals a groundbreaking approach to understanding Alzheimer’s disease. By integrating computational and functional methods, researchers at Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute (Duncan NRI) have identified potential risk factors and targets for therapeutic intervention. The breakthrough findings shed light on the complex causes of Alzheimer’s disease, which affects over 50 million people worldwide.

The study’s lead author, Dr. Juan Botas, emphasized that despite extensive genome-wide studies, the roles of many genes in Alzheimer’s disease were still unclear. “We addressed this issue by integrating published genome-wide association data with multiple computational approaches to identify genes likely involved in AD,” said Dr. Botas. This innovative approach enabled the researchers to pinpoint not only specific genes associated with increased risk but also those that could potentially modulate neuronal dysfunction.

The team systematically assessed 123 candidate genes for their potential impact on Alzheimer’s disease and found that reversing the alterations in 11 of these genes protected fruit flies from damage to their nervous system. Notably, one gene, MTCH2, emerged as a top contender for therapeutic purposes. The researchers discovered that reducing MTCH2 expression in fruit flies aggravated motor dysfunction, while restoring its expression reversed motor impairment and reduced tau accumulation.

“This finding supports further exploration of MTCH2 for therapeutic purposes and highlights the value of a combined computational and experimental approach to uncover main genetic players in Alzheimer’s disease,” said Dr. Botas.

The study’s authors note that this work was supported by NIH grants, underscoring the importance of continued research in this area. As scientists continue to unravel the complexities of Alzheimer’s disease, their findings hold promise for future therapeutic interventions and improved patient outcomes.