Day: April 18, 2023

Categories : Regenerative MedicineTags :

Cultured Cells may Restore Vision Lost to Photoreceptor Damage

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A preclinical study that produced progenitor photoreceptor cells and transplanted them into experimental models of damaged retinas has resulted in significant vision recovery. This finding marks a first step towards potentially restoring vision in eye diseases characterised by photoreceptor loss.

“Our laboratory has developed a novel method that enables the production of photoreceptor progenitor cells resembling those in human embryos,” said Assistant Professor Tay Hwee Goon, first author of the study published in Molecular Therapy. “Transplantation of these cells into experimental models has yielded partial restoration of the retinal function.”

The degeneration of photoreceptors in the eye is a significant cause of declining vision that can eventually lead to blindness and for which there is currently no effective treatment. Photoreceptor degeneration occurs in a variety of inherited retinal diseases, such as retinitis pigmentosa, a rare eye disease that breaks down cells in the retina over time and eventually causes vision loss, and age-related macular degeneration, a leading cause of vision impairment worldwide.

Asst Prof Tay and her team from Duke-NUS Medical School, the Singapore Eye Research Institute and the Karolinska Institute in Sweden, developed a procedure to grow human embryonic stem cells in the presence of purified laminin proteins. These proteins are involved in normal development of human retinas, and in their presence, stem cells could be directed to differentiate into photoreceptor progenitor cells responsible for converting light into signals that are sent to the brain.

When these cells were transplanted into damaged retinas, the preclinical models showed significant recovery of vision. A diagnostic test called electroretinogram also identified significant recovery in the retinas via electrical activity in the retina in response to a light stimulus. The transplanted cells established connections with surrounding retinal cells and nerves in the inner retina. They also survived and functioned for many weeks after transplantation.

Moving forward, the team hopes to refine their method to make it simpler and achieve more consistent results than earlier attempts to explore stem cell therapy for photoreceptor cell replacement.

“It is exciting to find these results, which suggest a promising route towards using stem cells to treat those forms of visual deterioration and blindness caused by the loss of photoreceptors,” said Dr Helder Andre, Head of Molecular and Cellular Research from Karolinska Institute’s Department of Clinical Neuroscience and a senior author of the study.

Associate Professor Enrico Petretto, Director of the Centre for Computational Biology at Duke-NUS and the study’s bioinformatics analysis lead, added: “Our method may also be useful for understanding the molecular and cellular pathways that drive the progression of macular degeneration, perhaps leading to the development of other therapeutic approaches.”

The next challenge for the researchers is to explore the efficacy of their method in models of photoreceptor degeneration that more closely match the human condition.

“If we get promising results in our future studies, we hope to move to clinical trials in patients,” said Professor Karl Tryggvason, from Duke-NUS’ Cardiovascular and Metabolic Disorders Programme, and the corresponding author of the study. “That would be an important step towards for being able to reverse damage of the retina and restore vision.”

Source: Duke-NUS Medical School

Categories : Diseases, Syndromes and ConditionsTags :

Real-world Testing Confirms Bulevirtide Efficacy in Treating Hepatitis D

On By ModernMedia
Colourised transmission electron micrograph of hepatitis B virus particles (colourised red and yellow). Credit: NIAID and CDC (Transmission electron micrograph image courtesy of CDC; colourisation by NIAID).

In 2020, bulevirtide (BLV) was conditionally approved for treating chronic hepatitis delta (CHD), an inflammation of the liver caused by hepatitis D virus (HDV). Now, as reported in the Journal of Hepatology, real-world studies confirm that long-term suppressive therapy with BLV monotherapy reduces viral replication and improves liver tests of these difficult-to-treat patients.

Two of the studies, led by Pietro Lampertico, MD, PhD, were designed to assess the effectiveness and safety of patients with advanced HDV-related compensated cirrhosis being treated with BLV 2mg monotherapy and the consequences of discontinuing this treatment.

“HDV is the most severe form of chronic viral hepatitis,” explained Dr Lampertico. “For many years, the only therapeutic option was the off-label administration of pegylated-interferon-alpha (PegIFNa), an approach characterised by suboptimal efficacy, an unfavourable safety profile and several contraindications.”

In a study of 18 patients with HDV-related advanced cirrhosis treated with BLV 2mg/day for 48 weeks, Dr. Lampertico and colleagues demonstrated significant virological, biochemical and combined response rates associated with improvement of liver function.

“The efficacy and safety of BLV monotherapy in patients with advanced compensated cirrhosis were unknown before this study. Virological and biochemical responses to BLV monotherapy that we observed in our difficult-to-treat patients with HDV-related compensated cirrhosis were similar to those shown in the phase III registration study,” Dr Lampertico noted.

In a case report, Dr Lampertico and colleagues demonstrated that HDV could be successfully eradicated from both serum and liver following a three-year course of BLV monotherapy. This was despite the persistence of HBsAg, in a patient with HDV-related compensated cirrhosis and oesophageal varices. During the 72-week off-BLV follow-up, liver biopsy, intrahepatic HDV RNA and hepatitis D antigen were undetectable, less than 1% of hepatocytes were HBsAg positive and all were negative for hepatitis B core antigen.

“We were surprised to demonstrate that HDV can be eradicated following a finite course of an entry inhibitor administered as monotherapy such as BLV 2mg/day, despite the persistence of HBsAg positivity,” commented Dr Lampertico.

In a study in JHEP Reports led by Katja Deterding, MD, investigators report the first data from the largest multicentre cohort of patients to date who were treated with BLV under real-world conditions. This included 50 patients with signs of significant portal hypertension, elevated pressure in the major vein that leads to the liver.

The retrospective analysis of 114 cases covered 4289 patient weeks of BLV treatment. Viral response was observed in 87 cases while hepatic inflammation improved, and treatment was well tolerated. More than 50% of patients showed a virologic response with less than 10% of patients not achieving an HDV RNA drop of at least 90% after 24 weeks. An improvement of biochemical hepatitis activity as measured by the liver enzyme alanine transaminase (ALT) values was observed regardless of virologic response. Investigators concluded that treatment was safe and well tolerated and associated with improvements in liver cirrhosis and portal hypertension with prolonged treatment.

“In line with other real-world cohorts and clinical trials our real-world study confirms the antiviral activity of BLV,” noted Dr Deterding. “We were surprised to see an improvement in biochemical hepatitis activity even in cases without viral response. Potential explanations for this phenomenon include anti-inflammatory properties of BLV.”

“This is the first time that patients with HDV-related chronic advanced liver disease can be treated with an antiviral therapy since 1977 when HDV was discovered. Long-term suppressive therapy with BLV 2mg/day has the potential to improve survival, of these difficult-to-treat patients for the first time in 45 years,” concluded Dr Lampertico. “We also found that BLV treatment can be successfully discontinued in some HDV patients who achieved long-term viral suppression while on therapy.”

HDV infection occurs when people become infected with both hepatitis B and D virus either simultaneously (co-infection) or acquire the hepatitis D virus after first being infected with hepatitis B (super-infection). According to the World Health Organization, HDV affects nearly 5% of individuals with a chronic infection resulting from hepatitis B virus (HBV). Populations that are more likely to have HBV and HDV co-infection include indigenous populations, haemodialysis recipients and individuals who inject drugs.

Source: Elsevier

Categories : Genetics Skeletal SystemTags :

Scientists Close in on the Genetic Determinants of Height

On By ModernMedia
Pexels Photo by Monstera

Human height is dictated by the sealing of the growth plates at the ends of bones that harden as a child develops. Along with diet and disease, heritability has long been known to be a factor determining height. Now, researchers report in Cell Genomics that cells in these plates determine the length and shape of bones and may partly predict final stature. The study identified potential “height genes” and found that genetic changes affecting cartilage cell maturation may strongly influence adult height.

“The study is really understanding the genetics of skeleton,” says paediatric endocrinologist and senior author Nora Renthal of Boston Children’s Hospital and Harvard University. “Height is a good starting point to understand the relationship between genes, growth plates, and skeletal growth because we can measure the height of every human being.”

To pinpoint height-associated genes, the team screened 600 million mouse cartilage cells to identify genes that, when deleted, can alter cell growth and maturation. These types of cellular changes in the growth plate are known to lead to variations in human height. The search turned up 145 genes mostly linked to skeletal disorders and are crucial for growth plate maturation and bone formation.

The team then compared these genes with data from genome-wide association studies (GWAS) of human height, which located “hotspots” along the entire human genome where “height genes” are located. But these regions can contain multiple genes, making it hard for researchers to track down and study an individual target.

“That’s kind of like looking for your friend’s house, but you only know the zip code,” says Renthal. “It’s difficult.”

The comparison revealed that genes affecting cartilage cells overlap with hotspots from human height GWAS, precisely locating genes in our DNA that likely play a role in determining our stature. Renthal and her team also discovered that many of the GWAS suggested height genes led to early maturation in cartilage cells. These findings suggest that genetic changes affecting cartilage cell maturation may influence height more.

Renthal notes that studies in mouse cells may not fully translate to humans, and GWAS are observational studies that cannot fully illustrate the cause and effects of height. But her study provides a novel method to bridge the two methods and provide new insights into human genetics.

Next, the team plans to use the method to understand hormones’ effect on cartilage cells. They will also look into some of the 145 genes that have no known connection to skeletal growth. The investigation may reveal new genes and pathways that play a role in the bones.

“I see patients with skeletal dysplasia, where there isn’t any treatment because genetics made their bones grow this way,” says Renthal. “It’s my hope that the more we can understand about the biology of the growth plate, the more we would be able to intervene at earlier times in growing skeletons and the life of a kid.”

Source: MedicalXpress

Categories : Gender Mental HealthTags :

Researchers Tie Sex-specific Genes to Depression

On By ModernMedia
Photo by Sydney Sims on Unsplash

Depression is widely reported to be more common in women than in men, with women twice as likely to receive a diagnosis than men. A new study published in Nature has found that there are differences between male and female genes and how they relate to depression.

In a genome-wide association(GWA} study, the McGill University researchers analysed the genomes of more than 270 000 individuals. They found that sex-specific prediction methods were more accurate in forecasting an individual’s genetic risk of developing depression than prediction methods that did not specify sex. The researchers found 11 areas of DNA that were linked to depression in females, and only one area in males.

In both males and females, genetic correlations were significant between the broad depression GWA and other psychopathologies; however, correlations with educational attainment and metabolic features including body fat, waist circumference, waist-to-hip ratio and triglycerides were significant only in females. Gene-based analysis showed 147 genes significantly associated with broad depression in the total sample, 64 in the females and 53 in the males.

Despite the biological processes involved in depression being similar in males and females, researchers found that different genes were involved for each sex. This information can be useful to identify future sex-specific treatments for depression.  “This is the first study to describe sex-specific genetic variants associated with depression, which is a very prevalent disease in both males and females. These findings are important to inform the development of specific therapies that will benefit both men and women while accounting for their differences,” says Dr Patricia Pelufo Silveira, lead author and Associate Professor in the Department of Psychiatry. “In the clinic, the presentation of depression is very different for men and women, as well as their response to treatment, but we have very little understanding of why this happens at the moment.”

Source: McGill University

Categories : HIVTags :

Abbott Partnership to Bring Affordable Blood-based HIV Self-test Kits to SA

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HIV testing is essential across the continuum of care but too often unavailable, unaffordable, or inaccessible. Abbott, the global leader in diagnostics and the fight against HIV, is partnering with Population Services International (PSI) and Unitaid to make HIV self-testing (HIVST) available at an affordable and accessible price. An initial 400 000 tests will be distributed within Africa.

This vital partnership serves as an early market access vehicle to enable affordable access to high-quality self-test kits in high HIV burden settings with a dire need for access to healthcare services, while mitigating risks such as increased supply chain costs and custom fees. People who test positive will undergo confirmatory testing and will be linked to antiretroviral treatment, keeping them healthy and helping reduce further transmission to others.

“With millions of people living with HIV worldwide, many of whom who do not know their status, receiving a diagnosis is a vital first step in accessing treatment”, says Bassem Bibi, divisional vice president, for Abbott’s rapid diagnostics business for EEMEA. “This is why this partnership is so important to Abbott as it reinforces our commitment to enabling people in Africa to live healthier, fuller lives, by improving testing capabilities through high quality and affordable blood-based HIV self-tests.”

“Self-testing has shifted the paradigm for HIV testing.  The HIV Self-Testing Africa (STAR) Initiative amassed compelling evidence that HIVST can reach more people than traditional diagnostics. It offers an alternative option to people living with HIV to find out about their status and to access anti-retroviral treatment services. Self-testing is a critical entry point to HIV prevention services for those testing negative, including the delivery of Pre-Exposure Prophylaxis (PrEP). It is also useful for screening in health facilities and to keep services going during COVID-19 and any future emergencies. We require more product options to meet the growing demand,” said Dr Karin Hatzold, Director of the STAR Initiative Project and Associate Director of HIV/TB Programs at PSI. “This important partnership under the early market access vehicle will make it easier for countries to acquire products and embed them in health systems. This will ensure that self-test kits are affordable to those who want to access them.”  

The Abbott HIV self-test kits will be distributed strategically to communities with inadequate access to healthcare services and will help build capacity to meet the UNAIDS 95-95-95 targets for 2025. The 95-95-95 targets stipulate that 95% of people living with HIV know their status; 95% of people who know their status are on antiretroviral therapy; and 95% of people on treatment have suppressed viral loads.

“Self-testing has helped us reach beyond health centres and make testing easier. This is critically important for vulnerable groups who are often at higher risk of HIV but may also be hesitant to access health services for fear of stigma, discrimination, and violence,” said Dr Philippe Duneton, executive director of Unitaid. “Making quality self-testing kits widely available and affordable is vital to reaching people at risk of HIV with the opportunity to test privately and access life-saving care.”