“Delete-To-Recruit” – Scientists Discover Simpler Approach to Gene Therapy

Repositioning genes awakens fetal hemoglobin to treat disease. CRISPR editing may change future gene therapy.

Researchers have discovered a promising new approach to gene therapy by reactivating genes that are normally inactive. They achieved this by moving the genes closer to regulatory elements on the DNA known as enhancers. To do so, they used CRISPR-Cas9 technology to cut out the piece of DNA separating the gene from its enhancer. This method could open up new ways to treat genetic diseases. The team demonstrated its potential in treating sickle cell disease and beta-thalassemia, two inherited blood disorders.

In these cases, a malfunctioning gene might be bypassed by reactivating an alternative gene that is usually turned off. This technique, called “delete-to-recruit,” works by altering the distance between genetic elements without introducing new genes or foreign material. The study was conducted by researchers from the Hubrecht Institute (De Laat group), Erasmus MC, and Sanquin, and published in the journal Blood.

Genes in our DNA contain the instructions for making proteins, which carry out many essential functions in cells. However, not all genes are active at all times. Some are only switched on when certain nutrients need to be processed, while others are active only during early development and later shut down. Proper cell function depends on tightly controlled gene activity. One important regulatory mechanism involves enhancers, which are segments of DNA that act like switches to turn genes on.

Bringing it closer

Enhancers can be located right next to the genes they regulate or positioned much farther away along the DNA.

“In this study, we discovered that it’s possible to activate a gene by bringing it closer to an enhancer,” said Anna-Karina Felder, one of the study’s first authors. Felder and her colleagues Sjoerd Tjalsma, Han Verhagen, and Rezin Majied accomplished this using CRISPR-Cas9, a gene-editing tool that works like precise molecular scissors.

Schematic representation of delete-to-recruit technology in sickle cell disease and beta-thalassemia. The black lines represent the DNA. In the starting situation (above), the adult globin genes (purple) are broken and fetal globin genes (pink and green) are inactive. The enhancer (blue) lies at some distance from the fetal genes. Application of delete-to-recruit technology (below) brings the enhancer closer to the fetal genes, activating them. To achieve this, the intermediate piece of DNA was cut out with CRISPR-Cas9 (scissors). Credit: Anna-Karina Felder/ Hubrecht Institute

“We directed the scissors to cut out a piece of DNA between an enhancer and its gene, bringing them closer together,” Felder explained. “In adult cells, this successfully reactivated genes that are normally only active during embryonic development.” The researchers call this new method of gene activation “delete-to-recruit.”

Faulty hemoglobin

The new strategy offers hope for people with sickle cell disease and beta-thalassemia. In these inherited blood disorders, the adult globin gene does not function correctly. As a result, the body cannot produce normal hemoglobin, the protein that carries oxygen in red blood cells. Without properly formed hemoglobin, red blood cells break down too quickly, leading to serious and lifelong symptoms such as anemia, fatigue, and eventually organ damage. Many patients rely on regular blood transfusions to manage these conditions.

Restarting the backup engine

Delete-to-recruit technology could be used to treat these patients by harnessing the fetal globin gene. This gene is naturally active before birth, and part of the hemoglobin produced within the fetus. Once the child is born, it is switched off. “In people with sickle cell disease or beta-thalassemia, it’s the adult globin gene—the main engine that powers red blood cells—that is broken. But fetal globin is like a backup engine. By switching it back on, we can repower the red blood cells and possibly cure these patients,” Felder says.

The team collaborated with researchers at Erasmus MC (Philipsen) and Sanquin (Van den Akker) to show that this strategy works in cells from human healthy donors and patients with sickle cell disease. Particularly important is that the team confirmed its efficacy in blood stem cells. These cells are responsible for producing the variety of blood cells in our body, including red blood cells. By reactivating fetal globin in blood stem cells, these cells can give rise to healthy red blood cells instead of broken ones.

New possibilities

“While we’re still in the early stages, this research lays important groundwork for the development of new gene therapies,” Felder says.

This goes beyond the scope of genetic blood diseases, as the new method could also be applied to other diseases where insufficient amounts of healthy proteins can be compensated by restarting a ‘backup engine gene’. The broader field of gene therapy could thus benefit from delete-to-recruit technology, because it uses a different approach than currently available therapies.

“Editing the distance to an enhancer, instead of the genes themselves, could offer a versatile therapeutic approach,” Felder concludes.

For patients with sickle cell disease and thalassemia, the new approach could—in the future—provide an alternative to the currently available gene therapy. While the existing gene therapy was approved for use in Europe in 2024, it is very expensive, which limits its accessibility. Moreover, this treatment modifies a globin repressor gene, which indeed causes reactivation of fetal globin, but may well have effects on other genes as well, with unknown consequences for the patient. Delete-to-recruit may circumvent both problems.

Funding: USEQ is subsidized by the University Medical Center Utrecht, USEQ is subsidized by The Netherlands X-omics Initiative, Research in the laboratory of WdL was financially supported by the EU Horizon 2020-funded Innovative Training Network ‘Molecular Basis of Human Enhanceropathies’ (Enhpathy,www.enhpathy.eu), under Marie Sklodowska-Curie grant, Research in the laboratory of WdL was financially supported by an NWO Groot grant from the Netherlands Organisation for Scientific Research (NWO), Research in the laboratory of WdL was financially supported by Oncode Institute Base Funding, Work in the laboratory of SP was supported by TKI Health Holland, Work in the laboratory of SP was supported by ZonMw PSIDER consortium TRACER, Work in the laboratory of SP was supported by EU Horizon Europe Pathfinder EdiGenT, Work in the laboratory of SP was supported by NWO Applied and Engineering Sciences Open Technology Programme, Work by the laboratory of EvdA was supported by Sanquin Blood Supply grant, Work by the laboratory of EvdA was supported by Sanquin research fund.

https://scitechdaily.com/delete-to-recruit-scientists-discover-simpler-approach-to-gene-therapy/

Vitamin D Boosts Breast Cancer Treatment Success by 79%, Study Shows

A clinical study in Brazil suggests that low-dose vitamin D supplements may significantly enhance the response of breast cancer patients to chemotherapy.

In a study conducted at São Paulo State University involving 80 women over the age of 45, low-dose vitamin D supplementation nearly doubled the rate of treatment response.

A study conducted at the Botucatu School of Medicine at São Paulo State University (FMB-UNESP) in Brazil found that low-dose vitamin D supplementation can improve the effectiveness of chemotherapy in women with breast cancer. The findings suggest that vitamin D may serve as an alternative to other drugs designed to boost chemotherapy response, especially those that are difficult to access.

The research, supported by FAPESP, included 80 women over the age of 45 who were preparing to begin treatment at the oncology outpatient clinic of the general and teaching hospital (“Hospital das Clínicas”) at FMB-UNESP. The women were divided into two groups: one group of 40 received 2,000 IU (international units) of vitamin D daily, while the other 40 received placebo tablets.

After six months of cancer treatment and supplementation, 43% of the women taking vitamin D saw their tumors disappear following chemotherapy, compared to 24% in the placebo group. All participants underwent neoadjuvant chemotherapy, a treatment used to shrink tumors before surgery.

“Even with a small sample of participants, it was possible to observe a significant difference in the response to chemotherapy. In addition, the dosage used in the research [2,000 IU per day] is far below the target dose for correcting vitamin D deficiency, which is usually 50,000 IU per week,” says Eduardo Carvalho-Pessoa, president of the São Paulo Regional Brazilian Society of Mastology and one of the authors of the article published in the journal Nutrition and Cancer.

Immunity

Vitamin D is a hormone that helps the body absorb calcium and phosphorus, both of which are essential for maintaining healthy bones. Recent research has also shown that vitamin D supports the immune system and helps fight infections and diseases, including cancer. However, most studies that have explored the connection between vitamin D and cancer have used high doses of the supplement.

This hormone is obtained primarily through exposure to sunlight and food. The recommended daily intake is 600 IU for those who are not deficient in the vitamin, and 800 IU a day for older people. The American Academy of Pediatrics recommends 400 IU of vitamin D per day for babies. It is important to note that too much can be toxic and cause vomiting, weakness, bone pain, and kidney stones.

After six months of cancer treatment and supplementation, 43% of participants using vitamin D saw their disease disappear with the use of chemotherapy, compared to 24% of the placebo group.

Most of the participants in the study had low levels of vitamin D, defined as less than 20 nanograms per milliliter (ng/mL) of blood. The Brazilian Society of Rheumatology recommends levels between 40 and 70 ng/mL. “With supplementation, levels increased throughout chemotherapy treatment, which reinforces a possible contribution to the patients’ recovery,” Carvalho-Pessoa told Agência FAPESP. “Vitamin D is an accessible and inexpensive option compared to other drugs used to improve the response to chemotherapy, some of which are not even included in the list of the Unified Health System [the Brazilian national public health network, known as the SUS, its acronym in Portuguese],” he adds.

For the researcher, the findings pave the way for further investigation into the auxiliary role of the substance in the response to cancer treatment.

“These are encouraging results that justify a new round of studies with a larger number of participants. This will allow a greater understanding of the role of vitamin D in increasing the response to chemotherapy treatment and, consequently, in the greater likelihood of breast cancer remission,” he concludes.

https://scitechdaily.com/vitamin-d-boosts-breast-cancer-treatment-success-by-79-study-shows/

Mother’s Obesity Reprograms Baby’s Future Health, Study Finds

Children of obese mothers are more prone to metabolic disorders, even when they eat healthily, and a new study uncovers an early cellular shift in the developing liver that may explain why.

Study explains increased risk of metabolic disorders in children born to obese mothers.

Children born to obese mothers face a higher risk of developing metabolic disorders, even if they eat healthily themselves. A new study from the University of Bonn provides an explanation for this effect.

In obese mice, certain cells in the embryo’s liver are reprogrammed during pregnancy, causing long-lasting changes to the offspring’s metabolism. The researchers believe these findings may also apply to humans. The study has been published in Nature.

The researchers focused on Kupffer cells, a type of macrophage or “big eater” involved in the body’s innate immune system. During embryonic development, these cells migrate to the liver, where they permanently reside. In the liver, they help defend against pathogens and remove aging or damaged cells.

“But these Kupffer cells also act as conductors,” explains Prof. Dr. Elvira Mass from the LIMES Institute at the University of Bonn. “They instruct the surrounding liver cells on what to do. In this way, they help ensure that the liver, as a central metabolic organ, performs its many tasks correctly.”

Permanently reprogram Kupffer cells. This changes their function, causes liver cells (hepatocytes) to accumulate fat and ultimately leads to a fatty liver. The graphic was created with BioRender.com (http://BioRender.com). Credit: AG Mass/University of Bonn

Changing the tune: From Beethoven to Vivaldi

Obesity appears to alter the regulatory role of Kupffer cells. This conclusion comes from mouse experiments conducted by Mass and collaborating research groups at the University of Bonn. “We were able to show that the offspring of obese mothers frequently developed a fatty liver shortly after birth,” says Dr. Hao Huang from Mass’s lab. “And this happened even when the young animals were fed a completely normal diet.”

The disorder seems to result from a type of “reprogramming” in the Kupffer cells of the offspring. These cells begin sending molecular signals that prompt liver cells to absorb more fat. Figuratively speaking, they stop conducting a Beethoven symphony and instead switch to a piece by Vivaldi.

More lipids (yellow, LD540) when exposed to molecules from Kupffer cells taken from the offspring of obese mice (right, HFDM). The image on the left shows liver cells exposed to factors from the offspring of mothers with normal weight (CDM). Cell nuclei are shown in cyan.

This shift already seems to occur during embryonic development and is triggered by metabolic products from the mother. These activate a kind of metabolic switch in the Kupffer cells and change the way these cells direct liver cells in the long term. “This switch is a so-called transcription factor,” says Mass. “It controls which genes are active in Kupffer cells.”

No fatty liver without the molecular switch

When the researchers genetically removed this switch in the Kupffer cells during pregnancy, the offspring did not develop a fatty liver. Whether this mechanism could also be targeted with medication is still unclear. The teams now plan to investigate this in follow-up studies.

If new treatment approaches emerge from this, it would be good news. The altered behavior of the Kupffer cells likely has many negative consequences. Fat accumulation in the liver, for example, is accompanied by strong inflammatory responses. These can cause an increasing number of liver cells to die and be replaced with scar tissue. The result is fibrosis, which gradually impairs liver function. At the same time, the risk that liver cells degenerate and become cancerous increases.

“It is becoming ever more evident that many diseases in humans already begin at a very early developmental stage,” says Mass, who is also spokesperson for the transdisciplinary research area “Life & Health” and a board member of the “ImmunoSensation2” Cluster of Excellence at the University of Bonn. “Our study is one of the few to explain in detail how this early programming can happen.”

In addition to the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE), the University of Vienna (Austria), Ghent University (Belgium), and Shanghai University (China) were involved in the study. The research was supported by the German Research Foundation (DFG, in particular SFB 1454 Metaflammation), the European Research Council (ERC), the Jürgen Manchot Foundation, the Boehringer Ingelheim Fonds and the European Molecular Biology Organization (EMBO).

https://scitechdaily.com/mothers-obesity-reprograms-babys-future-health-study-finds/

Your Own Immune Cells Could Be Involved in Parkinson’s

T cells are known for their role in defending the body, but new research suggests they may also be early actors in the mysterious progression of Parkinson’s disease. Scientists have now found that specific T cell activity intensifies well before clinical symptoms arise, hinting at a possible immune link to disease onset. LJI scientists have discovered that T cells may help detect Parkinson’s disease years before motor symptoms appear.Your T cells play a crucial role in defending the body against disease. However, sometimes they misfire, attacking healthy tissues in a phenomenon known as “friendly fire.”

This misdirected activity becomes a major concern in autoimmune diseases, where abnormal T cell responses lead to conditions like type 1 diabetes, rheumatoid arthritis, and inflammatory bowel disease.

In recent years, researchers at La Jolla Institute for Immunology (LJI) have found evidence that T cells may also be involved in the development of Parkinson’s disease. In the lab of LJI Professor Alessandro Sette, Dr. Biol. Sci., scientists discovered that many people with Parkinson’s have T cells that react to specific brain cell proteins, including alpha-synuclein and PINK1.

Earlier this year, Sette’s team published a study in npj Parkinson’s Disease identifying which subtypes of T cells respond to alpha-synuclein. The results provided more support for the idea that T cell activity may contribute to Parkinson’s. However, it remained unclear when in the course of disease this T cell involvement begins.

“We can see these reactive T cells in people after they develop Parkinson’s, but what happens before that?” says LJI Visiting Scientist Emil Johansson, Ph.D., a researcher in the Sette Lab and co-author of the study.

Now there are answers. In a new npj Parkinson’s Disease paper, Sette and his colleagues report that potentially harmful T cell activity is at its highest during the “prodromal” phase of Parkinson’s—the period that occurs years before a formal diagnosis is made.

“This T cell immunity could be a marker for early Parkinson’s treatment, even before people show symptoms,” says Sette, who was senior author on the new paper. “And there’s reason to think that treating Parkinson’s in the very early stages can lead to a better outcome.”

How the study worked

The prodromal period in Parkinson’s disease can last for decades before a person develops noticeable symptoms such as tremors and cognitive impairments.

Because prodromal Parkinson’s disease is very difficult to detect, the LJI team studied T cell reactivity in research volunteers at high risk of developing Parkinson’s disease. These volunteers had genetic risk factors for Parkinson’s and some had symptoms such as disrupted REM sleep cycles and loss of sense of smell, which can be early signs of Parkinson’s disease development.

The researchers used a technique called Fluorospot to learn more about T cells found in blood samples from these study volunteers. This technique revealed which volunteers had high levels of T cells that reacted to alpha-synuclein or PINK1—and when those T cell numbers were highest.

Sette and his colleagues found that potentially harmful T cells show up early on, well before the onset of noticeable motor symptoms, such as tremors. “You can see that T cell reactivity before diagnosis,” says Sette.

In fact, T cell reactivity to PINK1 was at an all-time high before diagnosis.

Sette warns against jumping to conclusions. Parkinson’s is a complex disease, and the new research doesn’t prove that T cells are actually driving the inflammation associated with Parkinson’s disease.

“Parkinson’s disease is associated with the destruction of nervous system cells. Does that destruction cause autoimmunity—or is the autoimmunity the cause of the disease? That’s the chicken-and-the-egg of inflammation in Parkinson’s disease,” says Sette.

“Certainly, the fact that this T cell reactivity is highest when patients are closest to a diagnosis is intriguing,” Sette adds. “The finding suggests T cells could have something to do with it.”

Next steps for helping patients

The new research may guide the development of early diagnostic tools. In the meantime, LJI scientists are looking for ways to block inflammation and protect brain cells.

As Johansson explains, some T cells actually help dial back inflammation to protect our tissues. “We want to see if there are specific T cells that are protective,” says Johansson. “Could they interfere in inflammation and maybe reduce the number of autoimmune T cells?”

Sette and his colleagues are also working to understand the role of T cells in other neurodegenerative diseases.

“We are very interested in diseases such as Alzheimer’s, for example, where a lot of progress has been made toward identifying people in very early stages of the disease progression,” says Sette.

https://scitechdaily.com/your-own-immune-cells-could-be-involved-in-parkinsons/

Millions of children at risk as global childhood vaccination rates plummet since 2010: Lancet

A landmark Lancet study shows global childhood vaccination progress has reversed since 2010, with measles coverage dropping in 100 countries. The pandemic created 12.8 million more unvaccinated children, with Nigeria and India accounting for half of cases. Researchers warn this increases risks of deadly outbreaks like polio and diphtheria. Vaccine misinformation and unequal access are undermining decades of immunization progress worldwide.

"Despite monumental efforts, progress has been far from universal" - Dr. Jonathan Mosser, IHME

With a significant decline in the progress made in global childhood vaccination rates since 2010, lives of millions of children are at vulnerable to preventable diseases and death, according to a new study published in The Lancet on Wednesday.

Key Points

1 Measles vaccinations declined in 100 countries since 2010

2 15.6M children missed DTP/measles shots during pandemic

3 Half of unvaccinated kids live in 8 countries including India, Nigeria

4 Vaccine misinformation worsening immunization gaps

The study led by researchers from the Institute for Health Metrics and Evaluation at the University of Washington, analysed coverage rates for 11 core vaccines for diseases like diphtheria, tetanus, whopping cough, and measles recommended by the World Health Organization (WHO) across 204 countries and territories.

The findings showed that between 1980 and 2023, worldwide vaccine coverage doubled against diseases such as diphtheria, tetanus, whooping cough (pertussis), measles, polio, and tuberculosis.

In addition, there was also a 75 per cent global decline in the number of children who had never received a routine childhood vaccine (also known as zero-dose children), falling from 58.8 million in 1980 to 14.7 million in 2019 before the Covid-19 pandemic.

But since 2010, progress has stalled or reversed in many countries. For example, measles vaccinations declined in 100 of 204 countries between 2010 and 2019, while 21 of 36 high-income countries experienced declines in coverage for at least one vaccine dose against diphtheria, tetanus, whooping cough, measles, polio, or tuberculosis, the research showed.

The Covid pandemic further exacerbated challenges, leading to sharp decline in global vaccine coverage.

The pandemic resulted in an estimated 15.6 million children missing the full three doses of the diphtheria-tetanus-pertussis vaccine or a measles vaccine between 2020 and 2023.

Nearly 16 million children also did not receive any polio vaccine, and 9.18 million missed out on the tuberculosis vaccine.

The four pandemic years (2020-2023) also saw around 12.8 million additional unvaccinated zero-dose children worldwide.

“Despite the monumental efforts of the past 50 years, progress has been far from universal. Large numbers of children remain under- and un-vaccinated”, said senior study author Dr Jonathan Mosser from the Institute for Health Metrics and Evaluation (IHME), at the varsity.

Besides global inequalities and challenges from the Covid pandemic, “the growth of vaccine misinformation and hesitancy also contributed to faltering immunisation progress,” he added.

Further, the global study showed that in 2023, more than half of the world’s 15.7 million unvaccinated children were living in just eight countries. These were primarily in sub-Saharan Africa (53 per cent) and South Asia (13 per cent): Nigeria, India, the Democratic Republic of Congo, Ethiopia, Somalia, Sudan, Indonesia, and Brazil.

“These trends increase the risk of outbreaks of vaccine-preventable diseases, including measles, polio, and diphtheria, underscoring the critical need for targeted improvements to ensure that all children can benefit from lifesaving immunisations,” Mosser noted.

The global analysis called for a greater need to strengthen routine childhood vaccination coverage, boost investment and targeted strategies to maintain progress, close immunisation gaps, and ensure equitable access to life-saving vaccines.

https://www.newkerala.com/news/o/millions-children-risk-global-childhood-vaccination-rates-plummet-2010-259

Novo Nordisk launches weight-loss drug Wegovy in India, priced at Rs 4,336.25 per dose

Novo Nordisk has launched Wegovy, India's first GLP-1 weight-loss injection, priced from Rs 4,336.25 per dose. The drug aims to tackle obesity by regulating appetite and improving metabolic health. While offering cardiovascular benefits, it may cause nausea, pancreatitis, and thyroid risks. The company emphasizes affordability with uniform pricing for initial doses.

"Obesity is not just a personal health concern—it is a chronic disease and a national epidemic that India cannot afford to ignore." – Vikrant Shrotriya, Novo Nordisk India

Danish pharmaceutical company Novo Nordisk on Tuesday launched its once-weekly injectable weight-loss drug Wegovy in India, at Rs 4,336.25 per dose.

Key Points

1 Wegovy is India's first GLP-1 weight-loss injectable

2 Priced at Rs 4,336.25 for starter doses

3 Targets brain appetite regulation for chronic weight management

4 May reduce cardiovascular risks but has side effects

Wegovy, a once-weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA), is the first and only weight management medication in India.

The drug, with semaglutide as the active ingredient, is indicated for both long-term chronic weight management and reduction in risk of major adverse cardiovascular events in people living with the condition.

The drug is available in five dosing -- 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, and 2.4 mg -- and comes with the convenience of an innovative, easy-to-use pen device.

The first three will be priced at 4,336 rupees, and the monthly price for the drug starts at Rs 17,345 per pen, the company said.

On the other hand, 1.7 mg is priced at Rs 24,280 per pen, and 2.4 mg is priced at Rs 26,015 per pen.

Wegovy is a prescription-only medication that has the potential to improve the quality of life for millions of Indians living with obesity or overweight, the company said.

"Obesity is not just a personal health concern -- it is a chronic disease and a national epidemic that India cannot afford to ignore. Recognising this, we are proud to announce that we are bringing Wegovy to Indians as a transformative and evidence-based therapeutic solution with the convenience of a world-class, state-of-the-art pen device," said Vikrant Shrotriya – Managing Director, Novo Nordisk India.

"Additionally, we have an India-specific price with the benefit of the same price for the first three dosing strengths. With this we are reaffirming our commitment to address India's growing burden of overweight and obesity," he said.

Notably, the drug comes with common side effects which include nausea, diarrhea, vomiting, constipation, and stomach (abdomen) pain. In people with type 2 diabetes, it can cause low blood sugar; and also raise issues like gas, stomach flu, heartburn, and runny nose or sore throat. Rodent studies have reported a risk for thyroid tumours or thyroid cancer, with Wegovy. Acute pancreatitis and gallbladder problems were also reported in studies with Wegovy.

Wegovy works by targetting key areas of the brain involved in appetite regulation and food intake. It reduces hunger, improves satiety, and cuts down food cravings, eventually inducing weight loss.

It also improves insulin resistance and has a beneficial effect on the reduction of cardiometabolic events and risk factors.

https://www.newkerala.com/news/o/novo-nordisk-launches-weight-loss-drug-wegovy-india-priced-rs-489

Haemophilia A: Low dose emicizumab effective, will reduce cost by over 50 pc, says ICMR study

A breakthrough ICMR study reveals low-dose emicizumab is just as effective as standard treatment for Haemophilia A. The reduced dosage slashes costs by over 50%, making therapy more affordable for patients. This is especially crucial in developing nations like India, where treatment access is limited. The findings promise better joint health and fewer bleeding episodes for sufferers.

"Low-dose emicizumab will reduce the cost of therapy by more than 50 per cent." – Dr. Manisha Madkaikar, ICMR

Low dose of emicizumab could be as effective as standard dose against Haemophilia A, according to a study led by the Indian Council of Medical Research (ICMR).

Key Points

1 Low-dose emicizumab matches standard treatment efficacy

2 Cuts lifetime costs by ₹7 crore per patient

3 Improves joint health and bleeding prevention

4 Makes therapy accessible in developing nations

Emicizumab is a bispecific monoclonal antibody used to treat hemophilia A -- a genetic bleeding disorder.

The drug works by mimicking the function of the missing or deficient clotting factor VIII (FVIII), enabling blood clotting to occur and preventing or reducing bleeding episodes.

As per the official government data, there are 27,000 haemophilia patients registered and 1, 40,000 patients expected to be affected in India.

Low-dose emicizumab can also be potentially a cost-effective treatment option in persons with hemophilia A, especially in developing countries, the study revealed.

A standard dose of emicizumab is priced approximately at $15,000.

“As the standard dose of the drug is expensive making it difficult for people from lower economic strata to access it, the ICMR led the study to understand its effectiveness even with a low dose,” said Dr. Manisha Madkaikar, Director of ICMR- Centre for Research Management and Control of Haemoglobinopathies (CRHCM) in Nagpur.

“Low-dose emicizumab will reduce the cost of therapy by more than 50 per cent resulting in the saving of more than 7 crore per patient for lifetime treatment assuming a life span of 50 years and average weight of 50 kg,” she added.

In the study, the scientists compared the efficacy and safety of low-dose emicizumab with those on low-dose factor (F)VIII prophylaxis via chart review.

Published in the Journal of Thrombosis and Haemostasis, the ICMR team showed that the direct cost of low-dose emicizumab was approximately $6,000 and that for low-dose recombinant FVIII prophylaxis used in the study was $6,282 (the cost may range from $3432 to $7920 depending on the type of factor).

“Our study successfully demonstrated that low-dose emicizumab is equally effective in the treatment of Haemophilia,” Madkaikar said

Haemophilia can typically lead to preventable joint damage. In about 80 per cent of cases, haemophilia manifests as bleeding, most frequently involving the large joints like knees, ankles, elbows, hip, and wrist, followed by deep bleeds affecting large body muscles.

Each bleeding episode requires attention, and patients take a prolonged time for recovery and severe complications could occur if any bleeding is not attended. Treatment with monoclonal antibodies like emicizumab are offering better protection with fewer infusions, especially for patients with inhibitors.

The study showed that low-dose emicizumab also improves bleeding prevention, joint health, and quality of life in patients with haemophilia.

https://www.newkerala.com/news/o/haemophilia-low-dose-emicizumab-effective-reduce-cost-50-pc-978

USC Researchers new AI implant promises drug-free relief for chronic pain

A groundbreaking wireless implant promises real-time, personalised pain relief using AI and ultrasound power, no batteries, no wires, and no opioids. Designed by University of Southern California (USC) and University of California, Los Angeles (UCLA) engineers, it reads brain signals, adapts on the fly, and bends naturally with your spine.

This groundbreaking device, detailed in Nature Electronics, represents a significant leap forward in pain therapy. While current spinal cord stimulators can be unwieldy and are hard-wired to batteries, the new device is designed to bend and twist with movement and is powered by a wearable ultrasound transmitter without the need for a battery.

It also harnesses machine learning algorithms to customise treatment for each patient. The work was led by Zohrab A. Kaprielian Fellow in Engineering Qifa Zhou, who is also a professor of ophthalmology at the Keck School of Medicine of USC.

At the heart of this innovation is its wireless power supply, eliminating the need for bulky batteries and complex wired interfaces that often require repeated surgeries.

The UIWI stimulator receives its energy from an external, wearable ultrasound transmitter (WUT).

Ultrasound offers a safe, effective, non-invasive method for deep-tissue penetration. The device converts mechanical waves into electrical signals through a phenomenon called the piezoelectric effect.

The core of the UIWI stimulator is a miniaturised piezoelectric element made from lead zirconate titanate (PZT), a highly efficient material for converting incoming ultrasound energy into the electrical power needed for stimulation.

"What truly sets this device apart is its wireless, smart and self-adaptive capability for pain management," Zhou said. "We believe it offers great potential to replace pharmacological schemes and conventional electrical stimulation approaches, aligning with clinical needs for pain mitigation."

Ph.D. candidate in the Zhou Lab and lead author Yushun (Sean) Zeng said the wireless smart miniaturized stimulator had the ability to produce sufficient electrical stimulation intensity by using ultrasound energy, resulting in a more personalized, targeted and localized treatment.

"This energy-converting type is critical for deep stimulation, as ultrasound is a non-invasive and highly penetrating energy in clinical and medical areas," Zeng said.

"By leveraging wireless ultrasonic energy transfer and closed-loop feedback system, this UIWI stimulator removes the necessity for bulky implanted batteries and allows for real-time, precisely adjustable pain modulation," added Zeng.

"From a clinical standpoint, incorporating deep learning-based pain assessment enables dynamic interpretation and response to fluctuating pain states, which is essential for accommodating patient-specific variability," added Zhou Lab Ph.D. candidate Chen Gong, also a lead author on the paper.

The system continuously monitors brain recordings, specifically electroencephalogram (EEG) signals, which reflect a patient's pain levels.

Harnessing AI to assess pain levels: A sophisticated machine learning model, based on a neural network called ResNet-18, analyzes these brain signals and classifies pain into three distinct levels: slight pain, moderate pain, and extreme pain.

This AI model boasts a 94.8% overall accuracy in distinguishing between these pain states. Adapting treatment as needed: Once a pain level is identified, the wearable ultrasound transmitter automatically adjusts the acoustic energy it transmits.

The UIWI stimulator can then sense the propagated energy and convert it into electrical intensity, stimulating the spinal cord. This creates a closed-loop system that provides real-time, personalised pain management.

The UIWI stimulator itself is flexible, bendable, and twistable, allowing for optimal placement on the spinal cord. The electrical stimulation it provides to the spinal cord works by rebalancing the signals that transmit and inhibit pain, effectively suppressing the sensation of pain.

Demonstrated Success in the Lab The Zhou Lab team tested the UIWI stimulator in rodent models, with results demonstrating its effectiveness for pain management.

Researchers successfully relieved chronic neuropathic pain caused by both mechanical stimuli (like a pin prick) and acute thermal stimuli (infrared heat).

Lab tests showed that treatment from the UIWI stimulator led to significant reductions in pain indicators. In one experiment to evaluate whether an animal associates an environment with pain relief, rodents showed a clear preference for the chamber where the pain management system was activated, further confirming the device's effectiveness. (ANI)

https://www.tribuneindia.com/news/health/usc-researchers-new-ai-implant-promises-drug-free-relief-for-chronic-pain/

Scientists find novel way to slow and even reverse aging of the heart

Scientists have developed a hybrid biomaterial that could help slow or reverse the aging of the heart.

• A new study examines how a lesser-known part of cell biology may impact the aging heart.
• Specifically, the scientists investigate the extracellular matrix, which helps support the structure of cells, among other things.
• The authors hope that their study might lead to innovative ways to slow and even reverse the aging of the heart.

As we grow older, the body’s organs and systems tend to slow and become less efficient, and the heart is no exception.

According to the authors of a new study, the extracellular matrix (ECM) may play a pivotal role in the decline in cardiac function that we see with age.

They hope that their research, which utilizes an innovative new material, may one day help us slow this process. Here, we will explain their study and what the future may hold.

We will also provide tips for reducing heart aging that you can start today.

What is the extracellular matrix?

The extracellular matrixTrusted Source (ECM) is a network of molecules and minerals that sits between cells. Often referred to as the cell’s “scaffolding,” it plays many vital roles.

Depending on where in the body it is, it generally provides structural support, stops different tissues from sticking together, enhances cell-to-cell communication, and assists in wound healing.

Why does it matter for heart health?

ECM and the aging heart

According to the authors of the recent paper, which appears in Nature MaterialsTrusted Source, “it is widely acknowledged that the mechanics, organization, and composition of the ECM vary with age.”

They explain that these ECM changes may play a part in the stiffening of the cardiac muscle that occurs as we grow older. Age-related changes trigger so-called cardiac fibroblasts, which can lead to fibrosis: A buildup of connective tissue, as seen in scarring.

Although fibrosis is an important function and helps repair heart tissue after damage, when it is uncontrolled, it leads to a stiffer, less flexible ECM. In the case of the heart, this can make it less efficient at pumping blood.

Focusing on the ECM is relatively novel. “Most aging research focuses on how cells change over time,” explains Jennifer Young, senior author of the study and assistant professor at the Mechanobiology Institute of the National University of Singapore. “Our study looks instead at the ECM and how changes in this environment affect heart aging.”

DECIPHER: A hybrid biomaterial 

To help uncover the role of the ECM in heart health, the team designed a new, hi-tech model called DECellularized In Situ Polyacrylamide Hydrogel-ECM hybrid (DECIPHER).

This model was created using heart tissue from a rat and a lab-created gel that shares physical properties with ECM.

Previously, the authors explain, it was unclear whether changes in cell signaling or changes in tissue stiffness were most responsible for age-related declines in heart function.

“The DECIPHER platform solves this problem,” explains Avery Rui Sun, first author of the study, in a press release. He explains how it allows “researchers to independently control the stiffness and the biochemical signals presented to the cells — something no previous system using native tissue has been able to do.”

In other words, they could adjust the model and see what happens when cell signalling occurs as it does in a young heart, but with an older, stiffer ECM. Conversely, they could mimic the biochemical signals of an aged heart with a young, flexible ECM.

They found that “young” cell signaling outweighed the negative effects of the stiffer ECM. In reverse, young cells placed on “aged” ECM showed signs of dysfunction.

This implies that “the biochemical environment around aged heart cells matters more than stiffness,” explains Young.

What does it all mean?

Medical News Today reached out to Nishant Kalra, MD, an interventional cardiologist, chief medical officer at VitalSolution — an Ingenovis Health company — who was not involved in the study.

“Surface molecules (ligands) found in young heart tissue can prevent the activation of fibrosis-promoting cells, even when the tissue is as stiff as aged heart tissue, which points to new ways to target the extracellular environment to slow heart aging,” he told us.

HUMAN STUDIES NEXT

“This work provides a platform for identifying molecular mechanisms and potential therapeutic targets to prevent or reverse age-related cardiac dysfunction. While promising, human translation requires further validation, as the study used rat cells.”— Nishant Kalra, MD

Although intriguing, it will be countless studies and many years before these results will lead to new treatments. However, there are many science-backed lifestyle changes that will support your heart as you age.

How to protect your heart as you age

We asked Kalra for some tips on maintaining heart health. “For lifestyle-based prevention of heart aging, the most evidence-based strategies are:”

• Regular aerobic exercise: At least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic activity per week
• Adherence to a healthy dietary pattern: Emphasize fruits, vegetables, whole grains, and lean proteins while limiting saturated and trans fats, cholesterol, and sodium, such as by adopting the Mediterranean or DASH diets.
• Stop smoking: Tobacco damages blood vessels and increases the risk of heart disease.
• Adequate sleep: Aim for 7–9 hours of quality sleep per night. Sleep deprivation can negatively impact heart health.
• Weight management: Obesity is a major risk factor for heart disease.
• Stress reduction: Find healthy ways to manage stress, such as exercise, meditation, or spending time in nature.

“These behaviors,” he continued, “are consistently associated with reduced biological and cardiovascular aging, as shown in large epidemiological studies and supported by the American Heart Association.”

MNT also reached out to Daniel Atkinson, MD, a family physician from the United Kingdom, working for a private healthcare company called Treated. He also advised reducing alcohol intake.

“Keep it below 14 units (roughly 4–5 drinks) per week, avoid drinking more than 3 drinks in any one session, and give your body (and heart and liver) a break from alcohol for at least one continuous 48-hour period each week.”
— Daniel Atkinson, MD

“Excess alcohol consumption carries a few health risks,” Atkinson said, “and among these is the effect it can have on raising blood pressure, which elevates your risk of heart disease.”

He explained how drinking alcohol in excess can weaken the heart muscles, making it more difficult for the heart to pump blood around the body.

https://www.medicalnewstoday.com/articles/scientists-find-novel-way-slow-reverse-aging-heart