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Diseases and Conditions

Unlocking the Secrets of Huntington’s Disease: Two Proteins with Opposing Effects

Researchers found that inhibiting GSK-3 led to less defects in the axonal transport process and less neuronal cell death, while inhibiting ERK1 led to more transport problems and more cell death.

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The study of Huntington’s disease has been a longstanding mystery in neuroscience. Researchers at the University of Buffalo have made significant progress in understanding the disease by identifying two specific signaling proteins that play opposing roles in its progression.

The mutated huntingtin protein (HTT) is responsible for causing Huntington’s disease, but how it leads to the degeneration of neurons remains unclear. However, researchers have found that HTT functions as a traffic controller inside neurons, moving different cargo along axons with the help of other proteins. Reducing the amount of non-mutant HTT can lead to neurological problems.

In this study, the researchers focused on two signaling proteins: GSK3ß and ERK1. They were expressed more in the neurons of Huntington’s disease patients than in normal neurons. The team used fruit fly larvae with a mutant HTT to understand how these proteins affect neuronal function.

When they inhibited GSK3ß, they found that it led to less defects in axonal transport and reduced neuronal cell death. On the other hand, inhibiting ERK1 resulted in more axonal blockages and cell death.

The researchers suggest that ERK1 may protect neurons in the face of Huntington’s disease, while GSK3ß may exacerbate the condition. This means that therapeutics could potentially target these signaling proteins differently to treat this severe neurological disorder.

The study was supported by several organizations, including the National Institute of Neurological Disorders and Stroke, the Mark Diamond Research Fund, and the BrightFocus Foundation.

This research is a significant step towards understanding the progression of Huntington’s disease. By identifying two proteins with opposing effects, researchers can now explore ways to develop treatments that target these proteins differently. This could potentially lead to new therapies for this devastating disease.

Diseases and Conditions

“Breaking Isolation: How Addressing Hearing Loss Can Preserve Social Connections Among the Elderly”

Providing hearing aids and advice on their use may preserve social connections that often wane as we age, a new study shows. Its authors say that this approach could help ease the loneliness epidemic that older Americans face.

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The article has been rewritten to improve clarity, structure, and style, making it understandable to the general public.

Breaking Isolation: How Addressing Hearing Loss Can Preserve Social Connections Among the Elderly

A recent study has shown that providing hearing aids and advice on their use may preserve social connections among older Americans. The researchers found that those who received treatment for hearing loss retained one additional social connection on average over a three-year period compared to those who did not receive any hearing therapies.

The study, led by researchers at NYU Langone Health as part of the ACHIEVE clinical trial, revealed that those given hearing aids had more diverse relationships and maintained deeper bonds than those who were not treated for hearing loss. The findings add to evidence that helping aging patients hear better can enrich their social lives and boost their mental and physical well-being.

Experts have linked both loneliness and hearing loss to depression, heart disease, and early death, among other concerns. A 2023 report on the ACHIEVE trial showed that hearing interventions may slow cognitive decline among those at highest risk for dementia.

The research team collected data about older adults with untreated hearing loss across four sites in Maryland, North Carolina, Minnesota, and Mississippi. The study is among the largest to date to explore if hearing care can help prevent weakening of social networks, having included nearly 1,000 men and women ages 70 through 84.

Half of the participants received hearing aids, counseling sessions, and personalized instruction with an audiologist, while the other half received instruction about exercise, strategies for communicating with healthcare providers, and further resources for healthy aging. To measure social isolation, the researchers assessed how regularly participants spent time with others, the size and variety of their social networks, and the depth of their connections.

Among the findings, the study revealed that before treatment, participants in both groups reported feeling equally lonely. Three years after the intervention took place, loneliness scores slightly improved among those who had received hearing care, while scores slightly worsened among those who did not.

Hearing aids and related audiology appointments cost an average of $4,700, which is usually paid out of pocket, notes Coresh, the founding director of the Optimal Aging Institute. The authors plan to continue following the participants for another three years and to repeat the study with a more diverse group of people.

In conclusion, addressing hearing loss may be a crucial step in preserving social connections among older Americans. By providing hearing aids and related care, we can help alleviate loneliness, improve mental and physical well-being, and potentially slow cognitive decline. As the nation’s social isolation epidemic continues to grow, it is essential that we prioritize hearing health and incorporate hearing aid coverage into Medicare as a means of addressing this critical issue.

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Alzheimer's

Lecanemab Demonstrates Favorable Safety Profile in Real-World Setting

In a recent study, researchers found adverse events were rare and manageable among clinic patients with very mild or mild Alzheimer’s disease who received lecanemab infusions.

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The Food and Drug Administration’s (FDA) approval of lecanemab in 2023 marked a significant milestone in the treatment of Alzheimer’s disease. This novel therapy has been shown to modestly slow disease progression in clinical trials. However, concerns about side effects, such as brain swelling and bleeding, have led some patients and physicians to hesitate about using the medication.

Researchers at Washington University School of Medicine in St. Louis conducted a retrospective study to investigate the adverse events associated with lecanemab treatment in their clinic patients. The study, published in JAMA Neurology on May 12, focused on 234 patients with very mild or mild Alzheimer’s disease who received lecanemab infusions at the Memory Diagnostic Center.

The results of the study are reassuring. Only 1% of patients experienced severe side effects that required hospitalization. Patients in the earliest stage of Alzheimer’s, with very mild symptoms, had the lowest risk of complications. This information can help inform patients and clinicians as they discuss the treatment’s risks.

“This new class of medications for early symptomatic Alzheimer’s is the only approved treatment that influences disease progression,” said Barbara Joy Snider, MD, PhD, a professor of neurology and co-senior author on the study. “But fear surrounding the drug’s potential side effects can lead to treatment delays. Our study shows that WashU Medicine’s outpatient clinic has the infrastructure and expertise to safely administer and care for patients on lecanemab, including the few who may experience severe side effects, leading the way for more clinics to safely administer the drug to patients.”

Lecanemab is an antibody therapy that clears amyloid plaque proteins, extending independent living by 10 months, according to a recent study led by WashU Medicine researchers. The medication is recommended for people in the early stage of Alzheimer’s, with very mild or mild symptoms. In this study, only 1.8% of patients with very mild Alzheimer’s symptoms developed any adverse symptoms from treatment compared with 27% of patients with mild Alzheimer’s.

“Patients with the very mildest symptoms of Alzheimer’s will likely have the greatest benefit and the least risk of adverse events from treatment,” said Snider. “Hesitation and avoidance can lead patients to delay treatment, which in turn increases the risk of side effects. We hope the results help reframe the conversations between physicians and patients about the medication’s risks.”

The study found that most cases of amyloid-related imaging abnormalities (ARIA), a side effect associated with lecanemab, were asymptomatic and only discovered on sensitive brain scans used to monitor brain changes. Of the 11 patients who experienced symptoms from ARIA, the effects largely resolved within a few months, and no patients died.

“Most patients on lecanemab tolerate the drug well,” said Suzanne Schindler, MD, PhD, an associate professor of neurology and a co-senior author of the study. “This report may help patients and providers better understand the risks of treatment, which are lower in patients with very mild symptoms of Alzheimer’s.”

Overall, the study demonstrates that lecanemab can be safely administered and tolerated by most patients in a real-world setting, especially those with very mild symptoms of Alzheimer’s disease. This information can help alleviate concerns about side effects and encourage more patients to consider treatment with this novel therapy.

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Anemia

Unveiling a New Gene: FANCX’s Crucial Role in Fanconi Anemia

Mutations in FANCX appear to cause a lethal form of Fanconi anemia, a finding that sheds light on unexplained pregnancy loss and offers new avenues for genetic screening.

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Fanconi anemia is a rare and aggressive genetic disorder that affects bone marrow function and increases cancer risk. Despite advances in treatment, many individuals with this condition do not survive into adulthood without bone marrow transplantation and regular cancer screening. However, a recent study has identified a new gene, FANCX, which plays a critical role in the Fanconi anemia pathway. This discovery sheds light on the severity of Fanconi anemia caused by mutations in FANCX.

Researchers from Rockefeller University’s Laboratory of Genome Maintenance, led by Agata Smogorzewska, have been studying the Fanconi anemia pathway and its associated genes for years. They discovered that FANCX is a previously unknown gene involved in this pathway, and its mutations result in a more severe form of Fanconi anemia.

The researchers began to suspect that Fanconi anemia patients hadn’t presented with FANCX mutations until now because these mutations are so severe. Without the protein produced by FANCX, it’s unlikely that a fetus will survive. Smogorzewska and her team started looking for FANCX mutations in families with multiple miscarriages, which led to the identification of several cases.

The findings of this study have significant implications for families affected by Fanconi anemia. With the help of Kasturba Medical College in India, the researchers identified a second family with two miscarriages, and studies revealed that the mutant protein from that family lacked normal function. This discovery may soon enable clinicians to screen for FANCX mutations during IVF, selecting only healthy embryos for implantation.

The study’s lead author, Agata Smogorzewska, emphasizes the importance of collaboration in rare disease research. She highlights the role of the Fanconi Cancer Foundation in facilitating research and coordinating publications with other researchers. The foundation makes a significant contribution to the advancement of knowledge in this area, allowing families, patients, clinicians, and researchers to collaborate and compete.

The discovery of FANCX as a new Fanconi anemia gene has far-reaching implications for our understanding of this condition and its management. It may soon be possible to help families that carry these mutations prevent Fanconi anemia in future pregnancies by screening for FANCX mutations during IVF. The researchers now know what they’re looking for, which brings hope to those affected by this rare and aggressive genetic disorder.

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