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Unlocking New Therapies: Largest Osteoarthritis Genetic Study Reveals Pathways to Treatment Advancements

Researchers have uncovered multiple new genes and genetic pathways that could lead to repurposing hundreds of existing drugs for osteoarthritis, the most common form of arthritis.

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A significant breakthrough in the understanding and treatment of osteoarthritis has been achieved through the largest genetic study conducted to date on the condition. The research, which involved analyzing data from nearly 2 million people worldwide, was recently published in Nature and represents a major collaborative effort among top academic institutions.

The study, led by Helmholtz Munich in collaboration with Rush University Medical Center, uncovered multiple new genes and genetic pathways associated with osteoarthritis. This has led to the identification of 69 key genes whose protein products are already targeted by approved drugs, potentially paving the way for the repurposing of hundreds of existing medications.

The findings could revolutionize the treatment of osteoarthritis, a condition affecting over 600 million people worldwide. By leveraging genetics and functional genomics data from diverse populations, researchers aim to develop more effective and personalized treatments, which could ultimately lead to disease-modifying therapies for this widespread condition.

“This study represents a significant leap forward in offering tailored therapies for osteoarthritis patients,” said Dino Samartzis, co-author and professor at Rush University Medical Center. “We are excited about the prospect of repurposing existing drugs to manage osteoarthritis more effectively.”

The need for disease-modifying therapies has long been emphasized by orthopedic specialists, who see firsthand how osteoarthritis affects quality of life. The researchers’ efforts to harness the power of genetics could bring hope to millions and accelerate the development of transformative treatments.

As Brian Cole, professor of orthopedics at Rush, noted, “This study takes us closer to developing targeted biologics that not only alleviate symptoms but also slow disease progression and ideally restore joint health.”

Eleftheria Zeggini, director of the Institute of Translational Genomics at Helmholtz Munich, emphasized the potential for precision medicine in this context. “With 10% of our genetic targets already linked to existing drugs, we’re poised to accelerate the development of transformative treatments for osteoarthritis,” she said.

The researchers stress the need for more genetically diverse studies and functional genomics data from global populations to further refine their findings. By integrating genetics with tissue-level molecular insights, the pathway to new, effective, and personalized treatments becomes increasingly attainable.

This groundbreaking study not only redefines our understanding of osteoarthritis but also provides a path toward repurposing safe, approved drugs, potentially slashing the time and cost to bring effective treatments to market. The collaboration among researchers and clinicians from across the globe is a testament to the power of team science in driving impactful discoveries that can change the trajectory of disease care for generations to come.

Alzheimer's

The Surprising Link Between Curiosity and Healthy Aging

Psychology literature has shown that curiosity tends to decline with age. Psychologists shows one type of curiosity can increase well into old age, contradicting prior research. Older adults who maintain curiosity and want to learn new things relevant to their interests may be able to offset or even prevent Alzheimer’s disease. Conversely, those who show muted curiosity and disinterest may be at risk for dementia.

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The secret to aging successfully may not be what you think. Instead of focusing on physical exercise or mental stimulation alone, research suggests that cultivating curiosity can play a significant role in maintaining cognitive health and even preventing Alzheimer’s disease. An international team of psychologists has found that older adults who maintain a curious mindset and seek out new knowledge relevant to their interests may be able to offset or prevent dementia.

This finding challenges prior research that suggested curiosity decreases with age. The study, published in the journal PLOS One, was led by UCLA psychologist Alan Castel and involved a large sample of participants between the ages of 20 and 84. The researchers aimed to tease apart two types of curiosity: trait curiosity (a general level of inquisitiveness) and state curiosity (a momentary feeling of curiosity experienced when engaging with specific topics).

To assess these forms of curiosity, the researchers asked participants to complete an online questionnaire and guess answers to hard trivia questions. Analysis showed that while trait curiosity did decline across the adult lifespan, state curiosity increased sharply after middle age and continued upward well into old age.

The study’s lead author, Mary Whatley, notes that this finding may be related to selectivity theory, which suggests that as people get older, they become more selective about what they want to learn. This aligns with research on lifelong learning, where many older adults engage in activities like taking classes or picking up hobbies.

Castel’s own work on memory has shown that people tend to quickly forget information that doesn’t engage their curiosity. Anecdotally, many older adults report that staying curious is crucial for maintaining cognitive health and preventing dementia.

This study was supported by the National Institutes of Health’s National Institute on Aging, the Leverhulme Trust, and the Alexander von Humboldt Foundation. The findings suggest that cultivating curiosity can be a key factor in healthy aging and may even help prevent or offset Alzheimer’s disease.

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Alzheimer's

“Unlocking Brain Resilience: Researchers Discover CLU Protein’s Potential to Protect Against Alzheimer’s Disease”

Recently approved Alzheimer’s drugs offer a step forward for treating the disease, but new therapeutic strategies are needed to complement them and provide personalized therapeutic approaches. Researchers have identified a potential strategy to protect against Alzheimer’s disease by increasing the clusterin protein (CLU).

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As scientists continue to search for effective treatments for Alzheimer’s disease, a recent study has shed light on a promising new approach. Researchers at Mass General Brigham have discovered that increasing levels of the “CLU” (clusterin) protein may protect against cognitive decline and potentially provide a complementary therapy to existing treatments.

Led by Dr. Tracy Young-Pearse, the research team used various models, including human brain tissue from over 700 participants and animal models, to uncover the molecular role of CLU in protecting against neurodegeneration. Their findings suggest that increasing CLU can prevent inflammatory interactions between brain cells called astrocytes and microglia, which are associated with heightened inflammation.

The study’s results have significant implications for the design and testing of new therapeutic strategies for Alzheimer’s disease. As Dr. Young-Pearse noted, “Increasing clusterin has the potential to prevent cognitive decline in a way that is different than and complementary to anti-amyloid therapies to promote brain resilience.”

CLU may also be beneficial for treating other age-related brain diseases, many of which share similar mechanisms of neuroinflammatory dysregulation. The researchers emphasize the importance of personalized therapeutic approaches, as individuals’ responses to CLU upregulation vary based on their genetics.

The study’s findings provide a crucial step forward in the search for effective treatments for Alzheimer’s disease and other age-related brain diseases. By understanding the role of CLU in protecting against neurodegeneration, researchers can develop new strategies to promote brain resilience and potentially prevent cognitive decline.

In conclusion, the discovery of CLU’s potential therapeutic benefits offers new hope for individuals affected by Alzheimer’s disease and other age-related brain disorders. Further research is necessary to fully explore this promising approach, but the findings of this study mark an important milestone in the pursuit of effective treatments for these debilitating diseases.

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Alzheimer's

Physical Activity in Middle Age May Help Prevent Alzheimer’s Disease

An increase in physical activity between the ages of 45 and 65 could help prevent Alzheimer’s disease, while inactivity may be detrimental to brain health.

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Physical Activity in Middle Age May Help Prevent Alzheimer’s Disease

A recent scientific study has shed light on the importance of physical activity in middle age for preventing Alzheimer’s disease. The research, published in Alzheimer’s & Dementia, highlights the need to promote physical activity among adults aged 45-65.

The study found that increasing physical activity during this period can help prevent Alzheimer’s disease, while a sedentary lifestyle may be detrimental to brain health. In fact, it is estimated that 13% of Alzheimer’s disease cases worldwide can be attributed to physical inactivity.

The World Health Organization (WHO) recommends at least 150-300 minutes of moderate activity per week or 75-150 minutes of vigorous activity per week. While extensive research has shown that exercise reduces the risk of Alzheimer’s disease by improving cardiovascular and mental health, this study suggests that physical activity may have a direct impact on the development of brain pathology associated with the disease.

The research team conducted a four-year follow-up of middle-aged residents of Catalonia with a family history of Alzheimer’s disease. Participants were classified as adherent (meeting WHO recommendations), non-adherent (doing less than the recommended amount of physical activity), and sedentary (doing zero minutes of physical activity per week).

The study found that participants who increased their physical activity to meet WHO-recommended levels showed less beta-amyloid accumulation, a protein that can impair neural communication when it accumulates in the brain. Moreover, this effect appeared to be dose-dependent; the greater the increase in activity, the greater the reduction in amyloid burden.

Non-sedentary participants also showed a greater cortical thickness in brain regions associated with Alzheimer’s disease. Cortical thickness is crucial for memory, and its thinning or atrophy (loss of volume) is an early sign of neurodegeneration.

“The findings reinforce the importance of promoting physical activity in middle age as a public health strategy for Alzheimer’s prevention,” emphasizes Eider Arenaza-Urquijo, ISGlobal researcher and lead investigator of the study. “Interventions aimed at promoting increased physical activity could be key to reducing the incidence of the disease in the future.”

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