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The pubic symphysis is a cartilaginous joint at the front of the pelvis, which experiences varying degrees of separation during pregnancy and childbirth. This separation, influenced by hormones such as relaxin and progesterone, is a normal physiological adaptation that facilitates childbirth by widening the pelvic girdle. However, excessive separation can lead to discomfort and functional impairment, a condition known as pubic symphysis diastasis. Understanding the nuances of this condition is crucial in providing adequate care and support for new mothers.

Dr. Das and her team embarked on a prospective observational cohort study at Regions Hospital in St. Paul, Minnesota, to explore the intricacies of pubic symphysis separation occurring with pregnancy and childbirth. The study aimed to quantify pubic symphysis separation in first-time mothers who underwent either vaginal delivery or cesarean section. The researchers meticulously followed 91 women, taking serial radiographs at multiple intervals: within 48 hours of delivery and at 6, 12, and 24 weeks postpartum. This detailed approach allowed the team to assess the extent of pubic symphysis separation and its correlation with various intrapartum factors, providing a comprehensive understanding of the condition.

Dr. Das and colleagues discovered that the average immediate postpartum pubic symphysis separation was 7.6 mm, with no significant difference between vaginal (7.18 mm) and cesarean deliveries (8.04 mm). Normal physiological separation is less than 5 mm in nonpregnant patients and between 6 to 14 mm in pregnant and postpartum patients. Separation of more than 10 mm and/or persistence of this separation may be associated with pain and functional impairment with movement. All patients in this study had resolution of the pregnancy and delivery separation to prepregnant levels of 5 mm or less within 6 weeks. Persistence of pain or functional impairment 6 weeks after delivery may indicate the presence of a more pathologic separation that occurs rarely in 0.005% to 0.8% of births, and that would need further evaluation by an orthopedic specialist.

The findings indicate that the mode of delivery does not significantly impact the extent of initial pubic symphysis separation. The research highlights that separation is a common occurrence, regardless of the delivery method, and underscores the body’s natural preparation for childbirth.

The study also revealed that black race and obesity were associated with increased pubic symphysis separation. This suggests that demographic factors, rather than the type of delivery, play a more substantial role in determining the degree of separation. The researchers emphasized the importance of considering these factors when managing and counseling pregnant women. Recognizing the influence of race and BMI on pubic symphysis separation can lead to more personalized care and support for women during and after pregnancy.

Normalization of pubic symphysis separation back to 4-5 mm typically occurred by six weeks postpartum, with minimal further regression up to six months. This regression was consistent across both delivery methods. The findings highlight the body’s remarkable ability to heal and return to a pre-pregnancy state. The natural regression process provides reassurance to new mothers that their bodies are equipped to recover from the changes brought about by childbirth.

Interestingly, the study found that no specific labor events, such as the use of certain drugs or the duration of second stage labor, were significantly related to the degree of pubic symphysis separation. This underscores that the physiological changes in the pubic symphysis are more related to inherent biological factors rather than the mechanical process of labor and delivery. This insight can help healthcare providers better understand and manage postpartum recovery, focusing on the natural healing process rather than aggressive surgical interventions.

The study’s results, as highlighted by Dr. Das and her colleagues, have several important implications for clinical practice and patient care. Firstly, the findings provide reassurance that pubic symphysis separation is a normal and temporary condition that typically resolves within six weeks postpartum. This knowledge can alleviate concerns for new mothers experiencing this condition, knowing that their bodies are following a natural healing process. Healthcare providers can use this information to offer reassurance and general conservative measures, helping to ease the anxiety that new mothers may feel about their postpartum recovery.

Secondly, understanding that obesity and racial differences can influence the degree of separation may help healthcare providers in counseling and managing expectations for affected women. Dr. Das and her team suggest that tailored advice and support can be given to women based on these demographic factors, improving their postpartum care and recovery experience. This personalized approach ensures that women receive the care and attention they need, based on their unique circumstances.

Lastly, the study suggests that conservative management remains appropriate for most women experiencing pubic symphysis separation, as significant regression occurs naturally without intervention. Dr. Das and her colleagues advocate for a patient-centered approach, focusing on supportive care and reassurance rather than unnecessary medical interventions. By emphasizing the body’s natural ability to heal, healthcare providers can help new mothers navigate their postpartum journey with confidence and ease.

Pubic symphysis separation during childbirth is a natural physiological process that supports the birthing process. Dr. Das and her team highlight that this separation is not significantly influenced by the mode of delivery but rather by demographic factors such as race and BMI. Most importantly, their research reassures that the separation usually normalizes within six weeks postpartum. This study contributes valuable knowledge to the field of obstetrics, emphasizing the body’s remarkable ability to adapt and recover during the postpartum period.

By shedding light on the factors influencing pubic symphysis separation and its natural regression, Dr. Das and her team have paved the way for better understanding and improved evidence-based care and support for new mothers, without unnecessary surgical intervention after childbirth.

Researchers have understood for a while that the relationship between alcohol consumption and atherosclerotic cardiovascular disease is largely dictated by the pattern of drinking; both the quantity of alcohol consumed, and the frequency of consumption must be taken into consideration. In general, heavy alcohol consumption and binge drinking increase the risk of atherosclerosis and associated cardiovascular complications, whereas frequent low-to-moderate consumption is protective against such disease. However, the mechanisms underlying this complicated relationship are not fully understood.

To address this, Redmond’s recent research focused on the protective mechanisms of moderate alcohol exposure in endothelial cells. Her 2021 study found that moderate alcohol protects against the action of the pro-atherogenic protein ‘serum amyloid A1’ (or SAA1 for short) in causing endothelial dysfunction. Specifically, SAA1 caused the endothelial monolayer to be more leaky and sticky, allowing monocytes to adhere to it.

It also caused the endothelium to produce more reactive oxygen species and inflammatory cytokines such as interleukin-6 and interferon-gamma. However, co-treatment with alcohol at moderate levels completely prevented these SAA1-induced pro-atherogenic changes. The study found that this protective effect of moderate alcohol on the endothelium was mediated in part through activation of the Notch signaling pathway, and in part through Notch-independent mechanisms.

The Notch pathway is crucial for regulating cell differentiation, proliferation, and apoptosis, and its stimulation by moderate alcohol exposure appears to maintain endothelial cells in a non-activated beneficial state. This state is characterized by reduced inflammatory responses and enhanced barrier function, which are essential in preventing atherosclerosis. The research demonstrated that moderate alcohol exposure led to increased activation of the Notch pathway in endothelial cells, enhancing the production of nitric oxide, a molecule vital for vascular health. Nitric oxide promotes vasodilation, reduces blood pressure, and inhibits platelet aggregation, all of which contribute to a lower risk of cardiovascular events.

In this study, Redmond and her team employed both in vitro and in vivo models to unravel the protective effects of moderate alcohol levels. In vitro experiments using cultured human endothelial cells revealed that moderate alcohol exposure upregulated the activity of eNOS, the enzyme responsible for nitric oxide production. This upregulation was accompanied by a reduction in markers of inflammation and oxidative stress. Additionally, in vivo studies in mice demonstrated that daily moderate alcohol consumption (two drink per day equivalent) improved endothelial function and reduced the formation of atherosclerotic lesions in carotid arteries, compared with ‘no-alcohol’ controls. These findings provide a mechanistic basis for the cardiovascular benefits associated with moderate alcohol consumption as reported in many epidemiological and population studies.

Conversely, Redmond’s 2023 study delved into the effects of high dose alcohol, such as that achieved during heavy binge drinking, on the endothelium. This research illustrated a stark contrast, whereby alcohol at high levels caused endothelial dysfunction. Specifically, high level alcohol exposure did not stimulate homeostatic Notch signaling;  it decreased endothelial barrier integrity, elevated inflammatory cytokine and reactive oxygen species, and increased cell adhesion molecule expression and the attachment of monocytes to the endothelial monolayer. As mentioned previously, all these changes are pro-atherogenic and increase the risk of cardiovascular disease. In addition, the researchers found that acetaldehyde, the primary breakdown product of alcohol in the body, similarly causes endothelial dysfunction suggesting a significant role for this metabolite in alcohol-related vascular damage.

Taken together, these studies highlight the critical importance of alcohol dose. The data suggest that while alcohol in moderation can be protective, increased levels of drinking negate these benefits and cause endothelial damage leading to vessel disease that may ultimately result in heart attacks and strokes.

From a public health perspective, these findings highlight the importance of emphasizing alcohol moderation in targeted educational campaigns. For clinicians, these insights can help to inform tailored advice for patients. For instance, individuals with a family history of cardiovascular disease or existing risk factors might need stricter guidelines regarding alcohol consumption.

The research also opens avenues for further investigation. Understanding the molecular mechanisms underlying the ‘double-edged sword’ effects of alcohol could lead to the development of targeted therapies that either mimic the benefits of moderate alcohol consumption, or mitigate the harmful effects of heavy consumption. Additionally, exploring the role of genetic and environmental factors in modulating the effects of alcohol on endothelial function could provide insights into personalized approaches to cardiovascular disease prevention and treatment.

Redmond’s research significantly advances our understanding of how alcohol affects cardiovascular health. By revealing the biphasic effects of alcohol on endothelial function, these results provide a nuanced perspective that highlights the importance of moderation. These insights not only contribute to scientific knowledge but also have practical implications for dietary guidelines and public health policies aimed at reducing the burden of cardiovascular disease.

: Making end-of-life decisions when critically ill can be both incredibly challenging and incredibly liberating, and numerous factors can influence someone’s decisions or their ability to confront such decisions at different points in their treatment journey. Identifying the factors and nuances that affect this decision-making process could assist healthcare professionals to support patients and their families to navigate these consequential choices.

At the end of life, if a person with motor neurone disease is dependent on their ventilation they can choose to keep this in place until their death or they can choose to withdraw this treatment once they feel it is no longer of benefit to them. In the UK, ventilation is considered a treatment, and it is a patient’s legal right to stop or refuse treatment at any time. Those dependent on their ventilation would quickly die once it is withdrawn, and this is a challenging area of care that is relatively underexplored.

A recent study led by Dr Eleanor Wilson which was published in BMC Palliative Care delves into the complexities of end-of-life decision-making for individuals with motor neurone disease who are dependent on home mechanical ventilation, offering valuable insights from patients, their families, and bereaved relatives.

The research aimed to fill the gaps in understanding how people with motor neurone disease and their families make decisions regarding the use of home mechanical ventilation at the end of life. The study involved interviews with 62 participants across the UK, including 16 individuals living with motor neurone disease, 10 family members, and 36 bereaved family members. These interviews highlighted experiences, challenges, and perspectives surrounding end-of-life care and the use of home mechanical ventilation.

One of the most poignant findings was the reluctance among participants to engage in conversations about end-of-life choices. This reluctance can be an important coping strategy and was often rooted in a desire to “live for the day,” reflecting the immense uncertainty faced by those with motor neurone disease. For some, discussing the end of life was seen as an admission of defeat or an unnecessary burden on their already strained emotional state. Dr Wilson and her colleagues noted that some individuals avoided these discussions altogether, defaulting the responsibility of decision-making to others, when the patient lost the capacity to make decisions.

Despite this hesitation, many participants made ‘selective’ decisions related to personal planning. These decisions included practical and emotional preparations, such as making legal arrangements, expressing preferences for care, or discussing specific aspects of their future with loved ones. This selective approach allowed them to maintain some control over their lives without confronting the broader, more daunting aspects of their condition.

The unpredictable nature of motor neurone disease made it challenging for patients and their families to plan for the future comprehensively. Instead, many opted to make decisions as needed, responding to immediate circumstances rather than hypothetical scenarios. This approach helped them manage the stress associated with the disease’s progression. Decisions about adjusting home mechanical ventilation settings or opting for specific treatments were often made based on the current state of health rather than long-term projections. Dr Wilson and her colleagues found that this “timely” decision-making process was a practical strategy to cope with the uncertainty and constant changes characteristic of motor neurone disease.

In contrast, some participants reported taking proactive steps, such as advance care planning and making decisions about withdrawing treatment. Such decisions provided a sense of empowerment. These proactive decisions allowed patients to exert some control over the timing and manner of their death, which was crucial for their psychological well-being. For instance, some patients detailed their wishes regarding the discontinuation of home mechanical ventilation in specific circumstances, ensuring their preferences were known and respected when they could no longer communicate them directly. Dr. Wilson’s study highlighted the importance of these proactive decisions in enhancing the quality of life for patients and providing peace of mind.

However, in cases where patients were unable or unwilling to make these critical decisions, the responsibility often defaulted to family members or healthcare professionals. This transfer of decision-making could be stressful for all involved, as family members had to balance their emotional turmoil with the practical aspects of care. Healthcare professionals, on the other hand, had to navigate the delicate task of honouring the patient’s wishes while providing the best possible care. Dr Wilson and her team emphasized the need for clear communication and robust support systems to aid families and caregivers during these challenging times.

The study underscores the complexity, evolving and relational nature of decision-making for individuals with motor neurone disease who rely on home mechanical ventilation. It reveals that decisions about end-of-life care are deeply personal and influenced by a myriad of factors, including the patient’s physical state, emotional readiness, and family dynamics. The findings highlight the need for healthcare providers to approach these conversations with sensitivity, ensuring that patients and their families are supported throughout the decision-making process.

By shedding light on the diverse experiences of those affected by motor neurone disease, this study contributes to a better understanding of the challenges they face and the ways in which they navigate the difficult choices surrounding end-of-life care. It calls for a nuanced approach to support, one that respects the individual’s autonomy while providing the necessary guidance and resources to help them make informed decisions. The insights gained from Dr Wilson’s research emphasize the need for ongoing dialogue and tailored support to help those with motor neurone disease and their families manage the emotional and practical complexities of living with and eventually succumbing to this disease. The work of Dr Wilson and her colleagues is a significant contribution to the field of palliative care, highlighting the human aspects of medical care and the importance of compassionate, patient-centred approaches in managing life-limiting conditions.

BPD is a chronic lung disease characterized by damage to the lungs and airways. This disease most commonly develops in premature newborns who cannot breathe well yet, and thus require oxygen therapy delivered via ventilators.

The guidelines followed by many neonatal intensive care units suggest setting ventilators to ensure that the volume of air moving in and out of the lungs in a single breath is between 4.5 and 6 milliliters per kilogram of body weight. However, studies have found that prolonged ventilation can increase the risk of lung injuries. This can contribute to the abnormal dilation of the trachea, increasing the resistance of airways and potentially leading to lung injury and scarring.

This lung injury, in premature infants, is called BPD, and when severe can require invasive procedures, such as tracheostomies. A tracheostomy involves cutting into a patient’s neck and creating an opening in the trachea, to facilitate the flow of oxygen into the lungs, through a tracheostomy tube. This tube is more stable than the endotracheal tubes used in the hospital and allows very long-term ventilation, for months to years, that can be provided in the home.

In infants, this procedure can lead to complications, further hospital admissions, and even death. Research investigating the care of premature infants is of utmost importance, as it could help to identify new therapeutic strategies to prevent or reduce ventilator-related lung damage, thus reducing the risk of severe BPD and the need for tracheostomies in premature infants.

Dr. Rebecca Rose, a Physician at Riley Hospital for Children and Associate Professor of Clinical Pediatrics at Indiana University is co-director of the interdisciplinary BPD inpatient team. This team meets regularly to discuss premature infants who still require ventilation through an endotracheal tube at 4 weeks of age to ensure consistency of care throughout their stay in the neonatal intensive care unit and improve long term outcomes. The team uses standardized assessments of real time data from the ventilator to tailor ventilator settings to the changing lung physiology as the baby ages. A recent paper examined the potential of carefully modulating the settings of ventilators to prevent air trapping, and decrease the severity of BPD and the need for tracheostomy.

The BPD team cares for patients in the neonatal intensive care unit at Riley Hospital for Children, which also includes a maternity center. Although doctors in this maternity center try to limit the use of invasive ventilators, many premature babies require them for several days, weeks, or months.

Dr. Rose and her colleagues collected data in their neonatal intensive care unit for a period of approximately four years, spanning from early 2017 to late 2021 as part of an ongoing effort to improve the quality of care and outcomes in premature infants. In late 2018, they introduced an interdisciplinary team of physicians, including pulmonologists, and neonatologists, who were trained on a protocol for assessing an infant’s need for bedside ventilation and adapting ventilator settings based on the patient’s lung mechanics.

This team, dubbed the “BPD Team”, implemented a strategy to assess lung mechanics and the interactions between an infant and the ventilator. These assessments could then guide changes in ventilator settings.

The team specifically focused their efforts on premature infants born before the end of the 29^th week of gestation, who were still on invasive mechanical ventilation (ventilator support through an endotracheal tube), which they categorized as being at high risk of developing severe BPD. These patients have already incurred injury to their lungs from the ventilator, and often require invasive ventilation for prolonged periods of time. Continued ventilation with “gentle ventilation”, the style of ventilator settings used to prevent BPD, in these patients can lead to ventilating only the less injured areas of the lung, creating areas of collapsed lung next to areas of overdistended lung.

For these high-risk infants, the team followed a set of recommendations designed to intervene early, to use larger breaths given less frequently to avoid air trapping and ensure that adequate positive pressure remains in the airways at the end of a breath cycle. These recommendations were designed to ensure that air from the ventilator inflates all areas of the lungs, and the patients exhale fully, decreasing air trapping in the lung and minimizing further damage in the lungs and airways.

Dr. Rose and her colleagues later analyzed the data and observations gathered in their neonatal intensive care unit to assess the effectiveness of the early interventions. This included the medical information and therapeutic outcomes of 207 infants, of which 75 were treated before the intervention and 132 afterwards.

The most premature infants participating in the study were born when they were at the 22^nd week of gestation, when their mothers were approaching the end of their 5^th month of pregnancy. The least premature were born at the 28^th week of gestation, when their mothers were in the 7^th month of pregnancy.

The team’s results were highly promising, as their intervention did appear to have beneficial results. By introducing their guidelines for adapting ventilation settings, they were able to significantly reduce the number of infants who required a tracheostomy after invasive ventilation.

While the difference in the patients’ average length of hospitalization before and after the intervention was not significant, the team did observe a trend indicating that the intervention helped some patients go home earlier. Specifically, the average length of stay in hospital before the intervention was 180 days, and this went down to 153 days after the intervention.

Overall, the recent study reported by Dr. Rose and her collaborators highlights the promise of early intervention strategies designed to adapt ventilation settings, to avoid unnecessarily exposing infants to highly intensive mechanical ventilation for prolonged periods of time. The intervention devised by the clinicians, which featured an inter-disciplinary team and ventilator assessment guidelines, was found to significantly reduce the need for tracheostomies.

These findings suggest that measuring changes in the lung mechanics of premature newborns and adapting ventilator settings accordingly could help to reduce ventilator-related injury to the lungs and airways, thus decreasing the severity of BPD. In the future, the work by Dr. Rose and her colleagues could inform the development of new protocols for neonatal intensive care units, which could help to improve the therapeutic outcomes for extremely premature newborns, limiting tracheostomy and home ventilation, and speeding up recovery.

Digital models that can incorporate pre-existing experimental data to accurately predict product quality and functionality are widely used in many manufacturing processes. However, despite the potential resource, time, and cost savings to be made, the pharmaceutical industry has remained largely steadfast in adhering to tried-and-tested methods, often citing the hesitation associated with introducing new technologies into established systems, alongside the risk of compromising final product quality. This is particularly pertinent since the production of medicines is tightly regulated, and attaining a precise product specification is crucial to optimise functionality and ensure patient safety.

Using computer-assisted modelling, new processes can be designed that require minimal additional preparatory experiments to determine the ideal manufacturing conditions. These operational processes can then be used to produce active pharmaceutical ingredients in a more timely, more sustainable and less expensive manner. This has the additional advantage of vastly increasing our understanding of the production process, ensuring that quality is embedded throughout every stage of production and mitigating the risk of a poorly functioning final product.   

Despite the considerable progress made in using digital modelling in manufacturing processes during recent years, a gap remains in the use of digital tools that encompass the entire production journey from the initial process design to the clinic-ready pharmaceutical product.

To address this, CMAC collaborated with colleagues throughout the UK to develop digital process models for a series of routine pharmaceutical manufacturing steps, including crystallisation, filtration, washing, and drying. They used small-scale, material-sparing experiments to validate and refine their preliminary models to improve accuracy.

Their aim was to produce high-quality particles of the active ingredient in a widely used anti-inflammatory pain medication administered in tablet form. They also considered the low solubility of their active ingredient in the patient and using a physiologically relevant model of the human gastrointestinal tract, understood that a particle with a smaller surface area would maximise absorption by the human body after ingestion.

Furthermore, they intended to demonstrate that it was entirely possible to tailor these processes and produce target particles of differing sizes while maintaining the quality of the resulting tablets.

First, the team used available published data to identify the most appropriate solvents, processing methods, working temperatures, and analytical monitoring approaches to fulfil their requirements. Additionally, they prepared themselves to tackle known issues that may adversely impact outcomes, such as materials adhering to equipment, resulting in the unwanted accumulation of particulate matter, potential transfer line blockages, or disruption of heat transfer.

Increasingly, the use of potent organic molecules to produce medicines is becoming the norm, resulting in lower production volumes, more complex manufacturing processes and the risk that the material used during development outweighs production volumes.

Here, we are introduced to a streamlined method that incorporates digital design tools with the repurposing of material and data produced in earlier stages. This requires considerably lower volumes of active ingredient during the multi-step model development process compared to those reported in previous research.

Using existing experimental data and material meant that many of the experimental processes used in traditional development approaches were unnecessary and therefore eliminated, saving time, money and other resources.

One of the major objectives of CMAC’s research was to gain an increased understanding of the process itself, as opposed to retrospectively optimising the models using the final product. Indeed, controlling particle size has been identified as one of the most crucial targets in improving bio-availability.

Through innovative exploratory processes, the researchers achieved the impressive feat of designing a model that is transferrable to different particle size targets. This means that no additional experimentation is needed prior to implementing this production method to other particle sizes.

The capacity to identify blockages within equipment transfer lines in multi-stage processes would reduce the need for additional experimental screening and promote continuous processes, thus decreasing time, resource, and cost pressures even further. Refined models that address these issues are needed to ensure consistent quality standards. CMAC’s team has emphasised the importance of fully characterising the materials throughout the process, thus ensuring a high-calibre final product and reducing wastage.

There is an urgent need for more integrated, rapid process development that optimises pharmaceutical production outcomes. However, challenges persist. Notably, impurity impact during manufacturing remains unpredictable, and there are obstacles to overcome in designing processing models that consider and optimise several quality indicators simultaneously.

The pioneering work of CMAC and its collaborators has undoubtedly paved the way for the accelerated advancement of this groundbreaking technology. Faster, cheaper manufacturing protocols are within reach, and the desire to eliminate the need for additional validation processes may soon be a reality.

This will assist in the more cost-effective, more sustainable production of high-quality, optimally performing medicines for the treatment of various human diseases, and may prove invaluable when new pharmaceuticals are required swiftly.

Maintaining health into old age is a key priority for many, but time is not kind to the body. As we age, complex biochemical mechanisms in our body can begin to malfunction, leading to chronic health problems. For instance, in many people, tissues can become less sensitive to the action of insulin, the hormone that controls blood glucose levels. This can potentially pave the way for diabetes, and serious complications such as diabetic neuropathy, which involves painful lesions and ulcers that typically appear on the legs and feet. Insulin sensitivity deficits, inflammation and oxidative stress can also play a significant role in neurodegenerative diseases, such as Alzheimer’s disease. In fact, Alzheimer’s is sometimes described as diabetes type 3.

There are currently no effective treatments for either diabetic neuropathy or Alzheimer’s disease. However, Prof. Christian Bréchot and colleagues have accumulated a wealth of pre-clinical data for a new therapy for potential use in both conditions. This is ALF5755, a protein originally discovered in the liver, and which has demonstrated exciting efficacy in a range of disease states. The protein can directly bind and inactivate reactive oxygen molecules that cause cellular damage. It acts as a tissue repair molecule, which means it drives tissue regeneration and counterbalances tissue lesions and it also has significant anti-inflammatory effects and can help to reduce insulin sensitivity deficits.

Interestingly, ALF5755 tends to have the greatest effect on unhealthy and inflamed tissues. It binds to another protein called fibrin that forms long strands on the outside of cell membranes. Once bound to extracellular fibrin, ALF5755 has a local anti-oxidant effect by binding reactive oxygen molecules, and then this affects large protein bundles called receptors that are studded in the cell membrane. The receptors then transmit these changes inside the cell itself, helping to amplify the effectiveness of HIP treatment.

However, healthy cells tend to be covered with another protein called fibrinogen, and have less fibrin, meaning that HIP is less likely to affect them. This mechanism forms a serendipitous ALF5755 targeting effect for inflamed tissues, and may help to avoid off-target effects in healthier tissues.

One of the most painful and debilitating conditions for which ALF5755 has significant potential is diabetic neuropathy. Up to one third of patients with diabetes may experience foot ulcers, and up to 60% of such wounds become infected, with a significant associated risk that the affected limb will need to be amputated. In diabetes, high blood glucose levels lead to small vascular lesions which can become inflamed, leading to an increase in reactive oxygen molecules. These processes can damage and destroy nearby nerves, and the lesions can degenerate to form painful ulcers that are very difficult to treat. At present, no treatments exist that can slow or prevent diabetic neuropathy.

However, ALF5755 has shown exciting pre-clinical effectiveness in addressing the mechanisms underlying diabetic neuropathy. For instance, one study in mice showed that ALF5755 treatment could protect neurons in the brain from being killed through overstimulation, by exerting its anti-oxidant effects. In a second study in diabetic mice, ALF5755 treatment enhanced skin wound healing, in part by reducing levels of inflammatory proteins in the wound margin.

Impressively, in a sophisticated rat model of type 2 diabetes in which diabetic neuropathy arises as the rat grows older, ALF5755 treatment enhanced nerve sensitivity and associated muscle function.

The ALF5755 protein has also shown significant potential in pre-clinical models of Alzheimer’s disease. Alzheimer’s involves characteristic protein plaques and tangles within the brain, but it also involves inflammation and oxidative stress, providing an opportunity for HIP to provide therapeutic benefit.

The researchers used a mouse model of Alzheimer’s in which mice demonstrate characteristic protein plaques in their brains, along with memory and learning defects. They used genetic techniques to overexpress the ALF5755 protein in the mice, and successfully demonstrated that it could significantly reverse learning and memory defects over 6 months, and that it also increased levels of anti-oxidant enzymes in the brain. In a key aspect, the study demonstrated that ALF5755 could cross the blood-brain barrier, a specialized lining found in the blood vessels within the brain that often prevents therapies from entering.

In terms of the safety of ALF5755 therapy, so far, phase 1 and 2 studies in healthy men and patients with acute liver diseases who received intravenous administration of ALF5755, at a range of concentrations, showed no adverse effects, suggesting that this drug is safe for clinical use. At present, the therapy is designed to be delivered as a subcutaneous injection, but Bréchot and colleagues are working to develop a capsule formulation that patients could take orally.

Both diabetic neuropathy and Alzheimer’s are significant sources of suffering for many in old age, with no currently available treatment options to alleviate this. Finding new treatments that can help people to increase their health span and live happy lives into old age would be transformative. Therapies such as ALF5755 look to be a step in the right direction.