Can a HIV drug help prevent dementia?

cleansing mechanism of the nuerons and HIV drug work to help prevent dementia
A common characteristic of neurodegenerative diseases such as Huntington’s disease and various forms of dementia is the build-up in the brain of clusters—known as aggregates—of misfolded proteins, such as huntingtin and tau. These aggregates lead to the degradation and eventual death of brain cells and the onset of symptoms.

One method that our bodies use to rid themselves of toxic materials is autophagy, or ‘self-eating,” a process whereby cells ‘eat’ the unwanted material, break it down and discard it. But this mechanism does not work properly in neurodegenerative diseases, meaning that the body is no longer able to get rid of the misfolded proteins.

In a study published today in Neuron, a team from the Cambridge Institute for Medical Research and the UK Dementia Research Institute at the University of Cambridge has identified a process that causes autophagy not to work properly in the brains of mouse models of Huntington’s disease and a form of dementia—and importantly, has identified a drug that helps restore this vital function.

The team carried out their research using mice that had been genetically-altered to develop forms of Huntington’s disease or a type of dementia characterized by the build-up of the tau protein.

Using mice, the team showed that in neurodegenerative diseases, microglia release a suite of molecules which in turn activate a switch on the surface of cells. When activated, this switch—called CCR5—impairs autophagy, and hence the ability of the brain to rid itself of the toxic proteins. These proteins then aggregate and begin to cause irreversible damage to the brain—and in fact, the toxic proteins also create a feedback loop, leading to increased activity of CCR5, enabling even faster build-up of the aggregates.

When the researchers used mice bred to ‘knock out’ the action of CCR5, they found that these mice were protected against the build-up of misfolded huntingtin and tau, leading to fewer of the toxic aggregates in the brain when compared to control mice.

This discovery has led to clues to how this build-up could in future be slowed or prevented in humans. The CCR5 switch is not just exploited by neurodegenerative diseases—it is also used by HIV as a ‘doorway’ into our cells.

The team used maraviroc to treat the Huntington’s disease mice, administering the drug for four weeks when the mice were two months old. When the researchers looked at the mice’s brains, they found a significant reduction in the number of huntingtin aggregates when compared to untreated mice.

The same effect was observed in the dementia mice. In these mice, not only did the drug reduce the amount of tau aggregates compared to untreated mice, but it also slowed down the loss of brain cells. The treated mice performed better than untreated mice at an object recognition test, suggesting that the drug slowed down memory loss.

Professor Rubinsztein added: “We’re very excited about these findings because we’ve not just found a new mechanism of how our microglia hasten neurodegeneration, we’ve also shown this can be interrupted, potentially even with an existing, safe treatment.”

“Maraviroc may not itself turn out to be the magic bullet, but it shows a possible way forward. During the development of this drug as a HIV treatment, there were a number of other candidates that failed along the way because they were not effective against HIV. We may find that one of these works effectively in humans to prevent neurodegenerative diseases.”

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Anakinra, the elixir of youth?

Revitalizing Aging Blood System with Anti-Inflammatory Drug

A recent study published in Nature Cell Biology has found that an anti-inflammatory drug used for rheumatoid arthritis may be able to reverse some of the effects of aging on the blood system in mice. The drug, called anakinra, has been shown to have rejuvenating effects on the body’s blood cell-producing stem cells, which can become affected by age and lead to decreased production of red and white blood cells, impaired DNA protection, and increased risk of blood cancers.

Investigating the Hematopoietic Stem Cell Niche

Lead author Carl Mitchell and senior author Dr. Emmanuelle Passegué, Director of the Columbia Stem Cell Initiative, investigated the environment, or niche, that blood stem cells are found in, instead of the cells themselves. They discovered evidence of inflammation and deterioration in the aging hematopoietic stem cell niche that could be responsible for their loss of function. Blocking the action of the inflammatory signal interleukin-1 beta (IL-1B) with the drug anakinra returned the blood stem cells to a much healthier state.

Looking to Translate Results to Humans

The research team now aims to find out if the same process could work in human clinical trials. They also want to understand if improving the health of the stem cell niche earlier in life, such as in middle age, could have even more rejuvenating effects. “Only by having a deep molecular understanding will it be possible to identify approaches that can truly delay aging,” says Passegué.

Promising Results for Healthier Blood Production

The results of the study indicate that strategies aimed at maintaining a healthier blood production system in the elderly hold promise. “These results indicate that such strategies hold promise for maintaining healthier blood production in the elderly,” says Mitchell. By rejuvenating the body’s blood cell-producing stem cells, the drug anakinra may offer a new way to extend healthspan and potentially lifespan in older adults.

Reference: Mitchell CA, Verovskaya EV, Calero-Nieto FJ, et al. Stromal niche inflammation mediated by IL-1 signalling is a targetable driver of haematopoietic ageing. Nat Cell Biol. 2023;25(1):30-41.

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Challenges of Treating Chronic Pain

Challenges of Treating Chronic Pain

Chronic pain is a complex and difficult condition to treat despite the progress in neuroscience research over the last two decades. A recent overview by Ferreira and colleagues has added to the growing body of evidence on the use of medicines for pain, highlighting the limitations of current medical treatments.

Assessment of Antidepressants for Chronic Pain

In recent guidance from the UK National Institute for Health and Care Excellence, only antidepressants were found to have a favorable balance of benefits and harms for chronic primary pain. However, Ferreira and colleagues found that the evidence for their effectiveness in a wider range of chronic pain conditions was limited, with only 11 of 42 comparisons showing some level of effectiveness, none of which was of high quality. This suggests that most people living with chronic pain are unlikely to experience significant relief from antidepressant treatment.

Alternative Options for Pain Management

Group exercise, led by qualified instructors, has been shown to be effective in managing pain symptoms and has many other health and well-being benefits. In addition, non-medical services such as mobility support, debt management, and social connection can be helpful for people living with pain. Social prescribing, which refers to linking people with appropriate local support, is a promising approach, but its effectiveness is still evolving.

The Importance of Personalized Care

A strong, empathetic relationship with a care provider is crucial for successful pain management. People living with pain value time to discuss their concerns and easy access to support, and personalizing care is crucial for successful pain management. Research has traditionally focused on measures like pain scales and physical function tests, but new research should aim to understand the broader experience of living with pain.

Public Involvement in Pain Research

Public involvement in health research is crucial to ensure that pain research is meaningful and relevant to those living with pain and their clinicians. Researchers must involve people living with pain in their studies and overcome the barriers to public involvement in health research. Building new partnerships between clinicians, people living with pain, and researchers is crucial to improve care and research for chronic pain.


Chronic pain is more than just a medical condition and the limitations of current medical treatments present an opportunity to change the way we think about pain and focus on the individual experience of living with it. All stakeholders must share the responsibility of building these new partnerships to improve care and research for chronic pain.



  1. Efficacy, safety, and tolerability of antidepressants for pain in adults: overview of systematic reviews. BMJ 2023; 380 doi: (Published 01 February 2023).
  2. Chronic pain (primary and secondary) in over 16s: assessment of all chronic pain and management of chronic primary pain .NICE guideline [NG193].
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Sickle cell cure with LentiGlobin


Sickle cell disease is a genetic disorder that affects the hemoglobin in red blood cells. It is caused by a single point mutation in the gene encoding β-globin (HBB), leading to the production of sickle hemoglobin and impaired red-cell function. Patients with sickle cell disease often have vaso-occlusive events, progressive vasculopathy, and chronic hemolytic anemia. These are associated with complications and an increased risk of early death. Current supportive treatment options can only manage the disease without halting its progression.


Sickle cell disease is a debilitating condition that affects millions of people worldwide. Current supportive treatment options can only manage the disease without halting its progression. HLA-matched sibling allogeneic hematopoietic stem-cell transplantation is a potentially curative treatment option, but it is limited by the fact that only a small percentage of patients have HLA-matched donors, and there is a risk of graft-versus-host disease and graft rejection, as well as the risk of transplantation-related death. Gene therapies that use autologous stem cells may overcome these hurdles and are advancing into clinical trials.


LentiGlobin for sickle cell disease (bb1111; lovotibeglogene autotemcel, Bluebird Bio) consists of the autologous transplantation of hematopoietic stem and progenitor cells (HSPCs) transduced with the BB305 lentiviral vector encoding a modified β-globin gene. This results in the production of an antisickling hemoglobin, HbAT87Q. HbAT87Q is a modified adult hemoglobin with an amino acid substitution (threonine to glutamine at position 87) designed to sterically inhibit polymerization of sickle hemoglobin. In this ongoing phase 1-2 study, the researchers optimized the treatment process in the initial 7 patients in Group A and 2 patients in Group B with sickle cell disease. Group C was established for the pivotal evaluation of LentiGlobin for sickle cell disease, and a more stringent inclusion criterion was adopted that required a minimum of four severe vaso-occlusive events in the 24 months before enrollment.


In this unprespecified interim analysis, the researchers evaluated the safety and efficacy of LentiGlobin in 35 patients enrolled in Group C. Included in this analysis was the number of severe vaso-occlusive events after LentiGlobin infusion among patients with at least four vaso-occlusive events in the 24 months before enrollment and with at least 6 months of follow-up. As of February 2021, cell collection had been initiated in 43 patients in Group C; 35 received a LentiGlobin infusion, with a median follow-up of 17.3 months (range, 3.7 to 37.6). Engraftment occurred in all 35 patients. The median total hemoglobin level increased from 8.5 g per deciliter at baseline to 11 g or more per deciliter from 6 months through 36 months after infusion. HbAT87Q contributed at least 40% of total hemoglobin and was distributed across a mean (±SD) of 85±8% of red cells. Hemolysis markers were reduced. Among the 25 patients who could be evaluated, all had resolution of severe vaso-occlusive events, as compared with a median of 3.5 events per year (range, 2.0 to 13.5) in the 24 months before enrollment. Three patients had a nonserious adverse event related or possibly related to LentiGlobin that resolved within 1 week after onset. No cases of hematologic cancer were observed



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Exploring the Dangers and Promise of TikTok’s Viral #MentalHealth Videos on ADHD

The social media platform TikTok has seen a surge in the popularity of videos related to attention deficit hyperactivity disorder (ADHD) during the COVID-19 pandemic. The #ADHD channel on the platform now has 2.4 billion views and content related to the mental disorder has been shared by both individuals with no medical credentials and licensed psychiatrists and therapists. While some argue that TikTok can destigmatize mental disorders, foster community, and make research accessible to a wider audience, others caution that it can lead to self-diagnosis, overwhelm unqualified content creators with requests for help, and perpetuate misinformation about ADHD.

One of the benefits of ADHD content on TikTok is that it makes strategies for managing the disorder more accessible to those who may not have access to traditional mental health resources. Many creators on the platform share their personal experiences and research on ADHD, often without seeking financial compensation. Some licensed professionals, such as Dr. Edward Hallowell, a renowned ADHD psychiatrist, have also used the platform to provide advice and education on the disorder.

However, there are also risks associated with the proliferation of ADHD content on TikTok. Some content creators, who may have no formal training or qualifications in mental health, are being treated as experts on the disorder. This can lead to confusion and misunderstandings about ADHD, and may discourage individuals from seeking professional help. In addition, the platform’s algorithm can surface misleading or false information about ADHD, further perpetuating stigma and misinformation about the disorder.

Overall, it is important for individuals seeking information about ADHD to be cautious about the sources they rely on and to seek out qualified professionals for accurate information and support. While TikTok can be a useful resource for learning about ADHD and connecting with others who have the disorder, it should not be the sole source of information or treatment.

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Dapagliflozin, a diabetic drug for heart failure?

Dapagliflozin is a type of medication known as a sodium-glucose co-transporter 2 (SGLT2) inhibitor that is used to treat type 2 diabetes. It works by helping the kidneys remove excess glucose from the body through the urine, which can help lower blood sugar levels.

Several clinical trials have been conducted to investigate the effects of dapagliflozin on heart failure. One such trial was the DECLARE-TIMI 58 study, which was a large, randomized, controlled clinical trial that enrolled 17,160 patients with type 2 diabetes and high cardiovascular risk. The study found that treatment with dapagliflozin significantly reduced the risk of cardiovascular death and hospitalization for heart failure compared to placebo.

Another trial, the DAPA-HF study, enrolled 4,744 patients with heart failure and reduced ejection fraction (a measure of how well the heart pumps blood) who were already receiving standard heart failure therapy. The study found that treatment with dapagliflozin significantly reduced the risk of hospitalization for heart failure and cardiovascular death compared to placebo.

In addition to its effects on cardiovascular events, dapagliflozin has also been shown to improve health status in patients with heart failure. The DELIVER trial, which enrolled patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF), found that dapagliflozin improved symptoms, physical limitations, and overall quality of life as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ). The study also found that dapagliflozin reduced the risk of cardiovascular death and worsening heart failure, particularly in patients with greater symptom burden at baseline.

Overall, the evidence suggests that dapagliflozin may be effective in reducing the risk of heart failure and cardiovascular events in patients with type 2 diabetes and high cardiovascular risk, as well as in patients with heart failure and reduced ejection fraction who are receiving standard heart failure therapy. However, it is important to note that dapagliflozin is not a treatment for heart failure, and it should be used in combination with other appropriate therapies for heart failure.


DECLARE-TIMI 58 study:
Title: Dapagliflozin in Patients with Type 2 Diabetes and Cardiovascular Disease.
Authors: Sabatine MS, Giugliano RP, Keech AC, et al.
Journal: New England Journal of Medicine. 2017 Nov 9;377(19):1813-1824. doi: 10.1056/NEJMoa1711303.

DAPA-HF study:
Title: Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction.
Authors: McMurray JJV, Solomon SD, Inzucchi SE, et al.
Journal: New England Journal of Medicine. 2019 Nov 14;381(20):1995-2008. doi: 10.1056/NEJMoa1911303.

DELIVER trial:
Title: Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER): A Multicenter, Randomized, Placebo-Controlled Trial.
Authors: Anker SD, Lainscak M, von Haehling S, et al.
Journal: Circulation. 2020 Jun 9;141(23):1935-1946. doi: 10.1161/CIRCULATIONAHA.119.044473.

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Blood pressure variability: a new and unique risk factor

Blood pressure variability is a new and unique factor that is gaining more and more attention in the medical community. It refers to the fluctuation of blood pressure over time, and it can be caused by a variety of factors including stress, exercise, and even the time of day.

One important aspect of blood pressure variability is that it can be measured and tracked. This can be done through the use of a blood pressure monitor, which can be worn on the wrist or upper arm and measures blood pressure at regular intervals throughout the day. By tracking blood pressure variability, individuals and their healthcare providers can get a better understanding of their overall cardiovascular health and identify potential risk factors for conditions such as hypertension and heart disease.

Research has shown that blood pressure variability is a strong predictor of future cardiovascular events, such as heart attack and stroke. In fact, studies have shown that individuals with higher levels of blood pressure variability are at an increased risk for these types of events. For example, one study found that individuals with high blood pressure variability were 63% more likely to experience a stroke compared to those with low blood pressure variability (reference: “Blood Pressure Variability and Risk of Stroke: A Meta-Analysis”, Zhang et al., Stroke, 2012). Another study found that blood pressure variability was associated with a 2.5-fold increased risk of heart attack (reference: “Blood Pressure Variability and Risk of Myocardial Infarction: A Meta-Analysis”, Song et al., American Journal of Hypertension, 2014).

So what can be done to reduce blood pressure variability and the associated risks? One effective way is through lifestyle changes, such as eating a healthy diet, exercising regularly, and reducing stress. These changes can help to lower blood pressure and reduce fluctuations over time. In some cases, medication may also be necessary to manage blood pressure and reduce variability.

It is important to note that blood pressure variability is a complex and multifaceted issue, and further research is needed to fully understand its impacts on cardiovascular health. However, what is clear is that blood pressure variability is a unique and important factor that should be taken into consideration when evaluating an individual’s overall cardiovascular health. By tracking and managing blood pressure variability, individuals can take steps to improve their heart health and reduce their risk of future cardiovascular events.

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Making mRNA Vaccines Easy to Understand: Their Potential Role in Cancer Therapy

In recent years, mRNA vaccines have garnered significant attention due to their role in the fight against COVID-19. But mRNA vaccines have the potential to do much more than just prevent infectious diseases – they may also have a future role in cancer therapy.

But before we dive into the potential of mRNA vaccines in cancer therapy, let’s first understand what mRNA vaccines are and how they work.

What are mRNA Vaccines?

mRNA, or messenger ribonucleic acid, is a molecule that carries genetic information from DNA to the protein-making machinery of cells. Essentially, mRNA acts as a blueprint for the production of proteins in the body.

mRNA vaccines are a type of vaccine that use a small piece of genetic material (mRNA) to stimulate the body’s immune system to produce an immune response against a particular disease. Unlike traditional vaccines, which use weakened or inactivated forms of the disease-causing virus or bacteria, mRNA vaccines do not contain live pathogens. Instead, they use a small piece of the virus’s or bacteria’s genetic code, which is delivered to the body in the form of mRNA.

How Do mRNA Vaccines Work?

When an mRNA vaccine is administered, it enters cells and is translated into proteins. These proteins are then displayed on the surface of cells, where they are recognized by the immune system as foreign invaders. The immune system then mounts an immune response against the proteins, producing antibodies that can recognize and neutralize the virus or bacteria.

In addition to generating an immune response, mRNA vaccines can also stimulate the production of T cells, a type of immune cell that plays a key role in protecting the body against cancer and other diseases.

The Potential of mRNA Vaccines in Cancer Therapy

One of the major challenges in cancer treatment is the ability to specifically target and kill cancer cells while leaving healthy cells intact. Traditional cancer therapies, such as chemotherapy and radiation, often have significant side effects because they can damage healthy cells as well as cancer cells.

mRNA vaccines have the potential to overcome this challenge by selectively targeting cancer cells while leaving healthy cells unharmed. This is because mRNA vaccines can be designed to specifically target proteins that are found only on the surface of cancer cells, allowing the immune system to specifically attack the cancer cells while leaving healthy cells untouched.

In addition to their ability to selectively target cancer cells, mRNA vaccines have several other potential advantages as a cancer therapy. They can be produced quickly and at a low cost, and they have a good safety profile, with few side effects.

mRNA vaccines are still in the early stages of development as a cancer therapy, but there are several clinical trials underway that are investigating their use in a variety of cancer types, including breast, ovarian, and pancreatic cancer. While it will likely be several years before mRNA vaccines are approved for use in cancer therapy, the potential for this innovative approach is exciting and holds great promise for the future.

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Improving Patient Compliance with Medication

Medication compliance, or the extent to which patients take their prescribed medications as directed, is an important factor in ensuring that patients receive the full benefits of their treatment. However, many patients may not be compliant with their medication regimens for a variety of reasons, such as forgetfulness, fear of side effects, or difficulty affording the medication.

Non-compliance with medication can have serious consequences. When patients do not take their medications as prescribed, their symptoms may not improve or may even worsen, increasing their risk of complications and the need for more expensive or invasive treatments. Non-compliance can also lead to poor health outcomes and increased healthcare costs.

To improve medication compliance, a variety of strategies can be used. For example, patients can be given tools to help them remember to take their medications, such as pill organizers or smartphone reminders. Simplifying the dosing schedule and providing education about the medication and its benefits can also help increase compliance.

Healthcare providers play a critical role in improving medication compliance. They can provide support and education to patients, addressing any concerns or barriers to compliance, and collaborating with other members of the healthcare team to ensure that patients receive the medication and support they need.

In conclusion, medication compliance is an important factor in ensuring that patients receive the full benefits of their prescribed treatments. By implementing strategies to improve compliance and working together with healthcare providers, patients can be empowered to take their medications as directed and achieve better health outcomes.

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Medical Appraisal Template

The dust has finally settled with regards to the Medical Appraisal Template 2022.

GP Tools is proud to announce that the form has been implemented in its entirety.

There are significant changes from the MAG form and we feel that it is a return to the halcyon days of appraisal when box ticking was yet to be discovered.

  • Appraisal now centers around a holistic approach to the Doctor’s experience in the previous 12 months.
  • Copious reflection notes are no longer recommeded.
  • Discrete CPD and QIA logging are completely optional.
  • Unless absolutely necessary attachments and documentary evidence are not required.
  • Greater emphasis on the Doctor’s personal wellbeing and health.
  • Cutting down the time spent on filling in forms and box ticking.
  • A simpler and easy to understand layout.
  • Overview of CPD and QIA activities.
  • No longer credits or time spent to be documented.

The NHS England Appraisal Team have done a great job in making the process easier for Doctor’s and hopefully Revalidation Officers and LAT’s around the country will follow suit.

Medical Appraisal Template 2022

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