Month: July 2025

Categories : Neurology Regenerative MedicineTags :

Scientists Discover the Mechanism for Peripheral Nerve Regeneration

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Weizmann Institute scientists have discovered hundreds of molecules that promote nerve regeneration in mice – and may even encourage growth in brain neurons

Top: Overexpression of genes from the B2-SINE family in retinal ganglion neurons led to accelerated growth after injury. Bottom: Ganglion cells after injury without B2-SINE overexpression. Credit: Weizmann Institute of Science

Unlike the brain and spinal cord, peripheral nerve cells, whose long extensions reach the skin and internal organs, are capable of regenerating after injury. This is why injuries to the central nervous system are considered irreversible, while damage to peripheral nerves can, in some cases, heal, even if it takes months or years. Despite decades of research, the mechanisms behind peripheral nerve regeneration remain only partially understood.

In a new study published in Cell, researchers from Prof Michael (Mike) Fainzilber’s lab at the Weizmann Institute of Science discovered that a family of hundreds of RNA molecules with no known physiological function is essential to nerve regeneration. Remarkably, the study showed that these molecules can stimulate growth not only in the peripheral nervous system of mice but also in their central nervous system. These findings could pave the way for new treatments for a variety of nerve injuries and neurodegenerative diseases.

For a peripheral nerve to regenerate, it must maintain communication between the neuron’s cell body and its long extension – the axon – which in humans can reach more than a meter in length. In a series of studies over the past two decades, Fainzilber’s lab has revealed key components of this communication: proteins that act like postal couriers, delivering instructions for the production of growth-controlling factors and other proteins, from the cell body to the axon. These molecular couriers also help assess the distance between the cell body and the axon tip, allowing the neuron to modulate its growth accordingly. Yet one central issue remained: What triggers the regenerative growth after injury, and why does this not happen in central nervous system cells?

“While the growth acceleration observed in our study is not yet sufficient to address clinical paralysis, it is definitely significant”

In the new study, Dr Indrek Koppel of Fainzilber’s lab, in collaboration with Dr Riki Kawaguchi of the University of California, Los Angeles (UCLA), examined a specific kind of gene expression in the peripheral nerves of mice following injury. The researchers were surprised to find that one day after damage, the neurons increased the expression of an entire family of short genetic sequences called B2-SINEs, whose role was previously unknown. These sequences do not encode any proteins, and because they are known for “jumping” around the genome, meaning that they can appear at the wrong place or time, they have a bad reputation. But the researchers found that after injury, the neurons began expressing many B2-SINE RNA transcripts, in parallel with other processes preparing the cell for regeneration and repair.

However, B2-SINE is an enormous family, comprising some 150 000 sequences scattered throughout the mouse genome. The initial analysis could not determine which of these were responsible for promoting growth. Dr. Eitan Erez Zahavi, also of Fainzilber’s lab, who led the new study alongside Koppel, used bioinformatics tools to identify 453 B2-SINE sequences that are highly expressed after injury, promoting nerve growth. Collaborating with international research teams, the scientists showed that this overexpression after injury is unique to peripheral nerve cells and does not occur in the central nervous system.

The periphery leads, the center follows

The researchers then tested whether B2-SINEs from peripheral nerve cells could also stimulate neuronal growth in the central nervous system. They induced retinal neurons in mice to overexpress RNA molecules of the B2-SINE type and observed faster regeneration after injury. A similar experiment in the mouse motor cortex – the brain region that controls muscle movement via long axons projecting to the spinal cord – showed that neurons expressing high levels of B2-SINE also regenerated faster than control neurons.

“There are still no effective treatments to accelerate nerve cell growth and regeneration,” Fainzilber notes. “While the growth acceleration observed in our study is not yet sufficient to address clinical paralysis, it is definitely significant. Of course, the path from basic research to clinical application is long, and we must make sure that enhancing growth mechanisms does not, for example, increase the risk of cancer.”

One final mystery remained: How do B2-SINE RNA molecules actually promote regeneration? With help from Prof Alma L. Burlingame’s group at the University of California, San Francisco, the researchers discovered that these RNAs promote a physical link between the molecular “couriers” carrying instructions for producing growth-associated proteins and the ribosomes that read these instructions and carry them out. This means that production of the critical factors takes place closer to the cell body rather than to the tip of the axon. The researchers believe that this signals to the neuron that it is “too small,” triggering a growth response.

“There are over a million sequences called Alu elements in the human genome, the human equivalent of B2-SINEs in mice,” says Fainzilber. “These molecules had been previously shown to bind to ribosomes and mail couriers, but why this happens was unknown. We’re now trying to determine whether Alu or other noncoding RNA elements are involved in nerve regeneration in humans.”

“Recovery from peripheral nerve injuries, or from systemic diseases like diabetes that affect these nerves, can be very slow,” he adds. “That’s why we’re now testing a therapy that might speed up regeneration by mimicking B2-SINE activity. This therapy involves small molecules that connect the couriers to ribosomes while keeping them close to the nerve cell body, promoting faster growth. We are conducting this research in collaboration with Weizmann’s Bina unit for early-stage research with applicative potential.”

Beyond promoting peripheral nerve regeneration, the new study also hints at an even broader prospect: regeneration in the central nervous system. “We are currently working with UCLA on a study showing that the mechanism we discovered plays a role in recovery from stroke in mouse models,” Fainzilber says. “Additionally, we’re collaborating with Tel Aviv University, Hebrew University and Sheba Medical Center to study its possible role in ALS, a progressive neurodegenerative disease. Neurodegenerative conditions affect many millions of people worldwide. While the road ahead is long, I truly hope we’ll one day be able to harness our newly discovered regeneration mechanism to treat them.”

Science Numbers

After injury, the axon of a peripheral nerve cell regrows at a rate of around 1 millimetre a day.

Source: Weizmann Institute of Science

Categories : Mental Health Neurodegenerative DiseasesTags :

Parkinson’s Drug Effective in Treating Persistent Depression

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Photo by Andrew Neel on Unsplash

In the largest clinical trial to date, pramipexole was found to be substantially more effective than a placebo at reducing the symptoms of treatment resistant depression (TRD) over the course of nearly a year, when added to ongoing antidepressant medication.

The trial, supported by National Institute for Health and Care Research (NIHR) and published in The Lancet Psychiatry, included 150 patients with treatment resistant depression, with equal numbers receiving 48 weeks of pramipexole or a placebo, alongside ongoing antidepressant medication.

Overall, the group taking pramipexole experienced a significant and substantial reduction in symptoms by week twelve of treatment, with the benefits persisting over the course of a year. However, there were also significant side effects, such as nausea, sleep disturbance and dizziness, with around one in five people on pramipexole dropping out of the trial as a result.

Professor Michael Browning, from the Department of Psychiatry, University of Oxford, and workstream lead in Mood Disorders for the NIHR Mental Health-Translational Research Collaboration (MH-TRC) Mission, who led the trial, said: ‘Effectively treating people who have not responded to first-line interventions for depression is a pressing clinical problem and there has long been an urgent need to find new treatments.

‘These findings on pramipexole are a significant breakthrough for patients for whom antidepressants and other treatments and therapies have not worked.

‘Pramipexole is a medicine licensed for Parkinson’s disease and works by boosting the brain chemical dopamine. This differs from the majority of other antidepressant medications which act on brain serotonin and may explain why pramipexole was so helpful in this study.

‘We now need more research focusing on reducing the side effects of pramipexole, evaluating its cost-effectiveness, and comparing it with other add-on treatments.’

Previous research into using the drug for depression had shown promise, but there had been limited data on its long-term outcomes and side effects until now.

Current guidelines for people with treatment resistant depression recommend adding new treatments, such as lithium or antipsychotics, to ongoing antidepressant treatment, but these have limited effectiveness and do not work for everyone.

Phil Harvey, 72, from Oxfordshire, was diagnosed with depression 20 years ago and tried different tablets and counselling but nothing worked. Eventually he had to take a year off work before retiring. He started on the trial in 2022.

He said: ‘Within a few weeks I felt the effects, it was amazing. I kept a diary which they gave us on how my mood was, motivation and how it improved. It was dragging me out of this dark black hole that I’ve been in for years.’

Participants were recruited from across the country, including as part of the NIHR-funded MH-TRC Mission mood disorder clinics, which are hosted at Oxford but located across the country. The clinics efficiently, and largely remotely, assess patients with difficult to treat mood disorders and offer them enrolment in research studies. The network can also support primary care services by providing assessment and treatment advice for patients who have not responded to initial treatment.

Source: University of Oxford

Categories : VaccinesTags :

Operation Dudula Blocks Babies from Getting Vaccines

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Vigilante group is controlling clinic queues in Johannesburg

Photo by William Fortunato on Pexels

By Kimberly Mutandiro

Mothers of newborn babies, turned away at public clinics in Johannesburg because they are not South African, say their children are missing out on lifesaving vaccines.

In recent months, vigilante group Operation Dudula has been taking control of clinic queues across Johannesburg, chasing away immigrants or telling them to stand separately from South Africans. It is alleged that some healthcare staff have been participating.

This is despite a 2023 ruling in the Gauteng High Court that pregnant and lactating women and young children should be granted free health care services regardless of their nationality. 

The court ordered the Gauteng Department of Health to change its policy denying immigrants healthcare, and to place notices on the walls at all healthcare facilities stating lactating women and children may not be denied access. This order is not being consistently complied with.

GroundUp visited the Jeppe Clinic last week and saw no such notice. There was a small group of Operation Dudula members pulling immigrants out of the queue and telling them to stand to one side.

Jane Banda, a Malawian national, was at the clinic. She has been struggling to get her seven-week-old baby vaccinated, but has been blocked every time by Operation Dudula. She fears her baby’s health may be at risk if she continues to miss essential vaccinations.

Aisha Amadu, an asylum seeker from Malawi, who has a two-year-old baby, had an appointment at Jeppe Clinic last week but was chased away by Operation Dudula.

Grace Issah, also from Malawi, has a 14-week-old baby who was due for a vaccine two weeks ago. But she has been chased away from clinics in Jeppe, Bez Valley and Hillbrow.

“I feel like giving up because it seems there is nothing that I can do. My husband has no money for private doctors,” she said.

Several other women said they have also been denied access to clinics in Malvern, Kensington, Rosettenville and Soweto.

The Socio-Economic Rights Institute (SERI) launched a case in the Gauteng High Court in 2024, on behalf of Kopanang Afrika Against Xenophobia (KAAX), the Inner City Federation, Abahlali BaseMjondolo, and the South African Informal Traders Forum.

The group is seeking an interdict to declare the actions of the vigilante group, which include denying healthcare to immigrants, unlawful. The matter was heard in June, and judgment was reserved.

Mike Ndlovu from KAAX says it is a constitutional right for everyone in South Africa to be able to access healthcare.

“What Operation Dudula and a few complicit nurses are doing is unconstitutional, a criminal act, and a betrayal of our democracy. Denying healthcare is a violation of basic human rights,” said Ndlovu.

Ndlovu called on healthcare workers to remember their professional duty: to care without discrimination.

Operation Dudula’s actions have been condemned by the South African Human Rights Commission.

Department of Health spokesperson Foster Mohale said the department is aware of the action by Operation Dudula, but denied that department staff members are involved.

“The health facility managers have been advised to alert the law enforcement agencies whenever they experience these protests because that is a security issue to enforce the law,” Mohale said.

Mohale did not respond to questions about whether the department has complied with the 2023 court order to put up the notices.

Zandile Dabula, spokesperson for Operation Dudula, did not respond to a request for comment. But Veli Ngobese, a member of the movement who was at Jeppe clinic on the day GroundUp visited, said: “We are targeting all people from outside the country. We want Home Affairs to start afresh. Foreign nationals who come into the country should come and invest because the ones we see are selling amagwinya [vetkoek], pushing trolleys, and selling peanuts, and we are the ones paying taxes.”

He said the group will be conducting daily protests until immigrants stop going to clinics.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Read the original article.

Categories : Emergency Medicine Injury & TraumaTags :

Unlocking Fast, Targeted Treatment for Trauma Injuries

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Photo by Mat Napo on Unsplash

A groundbreaking study by researchers at Rutgers Health has uncovered a way to precisely identify and target trauma sites in the body within minutes of injury. The findings, published in the journal Med (Cell Press), could revolutionise emergency care by enabling real-time diagnostics and site-specific treatments delivered within minutes of injury.

A team of scientists, led by Renata Pasqualini and Wadih Arap at the Rutgers Cancer Institute discovered something new about how the body reacts to injury. When cells are damaged, like in a major bone break, calcium levels shift, which causes certain proteins to change shape. These changed proteins, called the “traumome,” are only found in injured tissues and show up right after an injury happens. This discovery opens up a new way to treat injuries directly, without affecting healthy parts of the body.

“The moment trauma occurs, specific proteins undergo structural changes, creating a molecular footprint of injury,” said Arap. “This opens the door to delivering diagnostics or therapies directly to the site – without affecting healthy tissues.”

This discovery has relevance in emergency treatment because many medicines can affect healthy organs when they’re given too soon. With this new approach, doctors could deliver treatments like imaging agents, clotting factors or antibiotics directly to the injured area, which would help the body heal faster with fewer side effects.    

“Our long-term vision is a simple injection that autonomously finds and treats injury sites,” said Pasqualini. “This could be transformative for battlefield medicine and emergency trauma care, where every second matters.”

The team used advanced testing on a pig model with major injuries to find tiny protein pieces called peptides. These peptides are like guides that can find and stick to the specific proteins altered by injury. One of these peptides stands out because it can attach to a protein that changes shape when calcium levels rise after an injury. This makes it possible to use special scans, like PET or MRI, to see exactly where the injury is in the body.

The trauma-targeting peptide worked the same way in rats, which shows that this injury “signature” is similar in all mammals, including humans.

The work was supported by the Defense Advanced Research Projects Agency (DARPA), an agency of the U.S. Department of Defense, underscoring its strategic value in both civilian and military medical applications. “Non-compressible bleeding remains a leading cause of death among soldiers before they reach a hospital, and localised treatment could dramatically improve survival rates, which was the original impetus of this research,” said Jon Mogford, a study co-author and former DARPA official.

The next phase of research will involve linking therapeutic agents to the trauma site-homing peptides and testing them in animal models before moving to early human clinical trials. The team envisions translational applications ranging from battlefield medicine to civilian trauma response and possibly even sports injuries or surgical recovery.

“We are actively developing peptide-linked drugs and imaging agents based on this discovery,” said Arap. “The traumome concept may also have applications beyond trauma, including in surgery, inflammation and tissue regeneration.”

Source: Rutgers University

Categories : Mental HealthTags :

Strength Through Struggles – Why Men’s Mental Health Matters

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Photo by Elizeu Dias on Unsplash

In South Africa, men are four to five times more likely to die by suicide than women. The silence around men’s mental health has become a national crisis. Momentum Health is confronting the uncomfortable truth: traditional ideas of masculinity are costing South African men their lives. The need for a more inclusive and proactive approach to men’s health is urgent.

With men accounting for a staggering 37.6 suicides per 100 000 people2 and depression affecting over 27% of South Africans3, the economic and human cost of ignoring men’s overall wellbeing has reached a breaking point. Mental health-related absenteeism alone costs the economy billions every year, a price tag that extends far beyond financial metrics into affected families and communities.

“We’ve long lived in a society that praises men for physical strength but punishes them for emotional vulnerability. While this is slowly changing, it’s not happening fast enough to make real impact,” says Damian McHugh, Chief Marketing Officer at Momentum Health. “This is why we’re challenging South Africa to redefine what strength really means. True strength is not silently suffering; it’s having the courage to reach out before crisis hits.”

A New Narrative for Men’s Health

In many communities across South Africa, men delay seeking medical help until conditions become critical and avoid mental health services despite growing internal struggles.

“When we tell boys to ‘man up’ we’re essentially telling them to disconnect from their emotional and mental wellbeing,” McHugh explains. “At Momentum Health, we believe real strength lies in connection to yourself, to professional support and to your community. That is why our approach integrates physical, mental, emotional and financial wellbeing, rather than treating them as separate issues.”

This holistic approach sets Momentum Health apart from conventional healthcare models that focus only on symptoms instead of the whole person.

The New Frontline for Men’s Mental Health

According to the 2025 Digital Report for South Africa5, 78.9% of the population are now online, with mobile connectivity exceeding 193% due to multiple device ownership. Recognising that many men would rather engage privately through an app than visit a therapist’s office, Momentum Health has deployed technology to meet men where they are.

“Technology is a powerful equaliser,” says McHugh. “It breaks down barriers of stigma, geography, and access. By meeting men in the digital spaces, they already inhabit, we’re not just offering support, we are changing the way mental health care is delivered.”

The Hello Doctor platform lets men chat privately with health experts right on their phones. It gives them a safe, non-judgmental space to talk about their mental health without feeling embarrassed. This service isn’t just offering help; it’s changing the way mental health care works in South Africa.

Health and Wealth: Two Sides of the Same Coin

The link between health and financial wellbeing is clear. Poor health can derail financial goals, while financial stress can strain mental and emotional resilience. Momentum Health’s integration of financial and health services addresses a critical reality: mental health struggles and financial problems can create a devastating downward spiral.

“You cannot separate these aspects of wellbeing and expect sustainable outcomes. When we say, ‘your health is your wealth,’ we are talking about a fundamental truth: without mental and physical resilience, financial success becomes meaningless,” says McHugh.

Creating a Culture of Support

South African men must take a proactive stance, not just for themselves, but for their families, their communities and future generations.

“This is not about perfection. It is about progress,” says McHugh. “And this is not just about saving lives, though that alone would be enough, it is about transforming what it means to be a man in today’s society.”

Categories : Cardiovascular DiseaseTags :

P2Y12 Drugs Preferable to Aspirin for CVD Prevention in Coronary Artery Disease

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Findings support use of P2Y12 therapy instead of aspirin for long term prevention

Source: Wikimedia CC0

Giving a P2Y12 inhibitor anti-clotting drug to patients with coronary artery disease is associated with lower rates of cardiovascular death, heart attack and stroke compared with traditional aspirin, with no increased risk of major bleeding, finds a study published by The BMJ.

P2Y12 inhibitors are often given to patients alongside aspirin (“dual therapy”) after percutaneous coronary intervention (PCI) – a procedure to widen or unblock a coronary artery – to help prevent cardiovascular events including heart attack and stroke.

After several months, patients are usually switched from dual therapy to lifelong aspirin, but some trials have suggested that a P2Y12 inhibitor may be more effective for long term prevention than aspirin.

To explore this further, researchers analysed individual patient data from five randomised clinical trials involving 16 117 patients (average age 65; 24% women) who were assigned to a P2Y12 inhibitor (clopidogrel or ticagrelor) or aspirin after completing dual therapy following PCI.

After an average follow-up period of around 4 years, P2Y12 inhibitor therapy was associated with a 23% lower risk of an outcome that combined cardiovascular death, heart attack, or stroke, compared with aspirin, with no significant difference in major bleeding. This means that for every 46 patients taking a P2Y12 inhibitor instead of aspirin after dual therapy, one cardiovascular death, heart attack, or stroke would be prevented.

When considering outcomes individually, P2Y12 inhibitor therapy reduced heart attacks and stroke compared with aspirin. However, all-cause death, cardiovascular death, and stent thrombosis were similar between the treatments.

The researchers acknowledge that some changes in the original design of some trials were needed to create uniform data, and that certain characteristics of individual trial populations may reduce the generalisability of the findings.

But they say no significant difference in major bleeding between groups was seen, and results were consistent after further analyses accounting for factors such as age, sex, geographical region, smoking, previous heart attack or stroke, underlying conditions and medication history, suggesting they are robust.

“Overall, this study supports preferential P2Y12 inhibitor monotherapy prescription over aspirin due to reductions in major adverse cardiac and cerebrovascular events (MACCE) without increasing major bleeding in the medium term,” say researchers in a linked editorial.

However, they note that “medium term efficacy does not necessarily extend lifelong, which is the duration we advise patients to continue these medications.”

As such, they suggest that “a large-scale globally representative trial directly comparing different monotherapy strategies (including discontinuation) with extended follow-up would benefit our understanding of the long-term impact of P2Y12 inhibitor monotherapy across the treatment class for secondary prevention following PCI.”

Source: BMJ Group

Categories : Lab Tests and Imaging NeurologyTags :

Researchers Discover a Significant Problem in Brain Imaging, Identify Fix

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Photo by Mart Production on Pexels

In a new study, investigators from McLean Hospital (a member of Mass General Brigham), Harvard Medical School, and the National Institute on Drug Abuse Intramural Research Program (NIDA-IRP) discovered that the tendency of people’s arousal to wane over the course of brain scans has been distorting the brain connection maps produced by functional magnetic resonance imaging (fMRI).

The study is out now in Nature Human Behaviour.

The team found that as people’s arousal levels dwindle during an fMRI, such as if they become more relaxed and sleepy, changes in breathing and heart rates alter blood oxygen levels in the brain—which are then falsely detected on the scan as neuronal activity.

“You’re laying down in a snug scanner for quite some time, often with only a low-engagement button press task to attend to or nothing to do at all, as the scanner monotonously hums and vibrates around you,” said first author Cole Korponay, PhD, MPA, a research fellow at the McLean Hospital Imaging Center. “These arousal-dampening conditions create the illusion that people’s brain connection strengths continuously inflate throughout the scan.”

fMRI scans are commonly used to non-invasively map brain connectivity, but the technique relies on changes in brain blood oxygen to indirectly measure neuronal activity. It is therefore vulnerable to “noise” from other processes that can affect blood oxygen – such as changes in breathing and heart rates.

And because breathing and heart rate patterns are closely tied to arousal levels, changes in arousal can introduce significant noise into fMRI data. Problematically, the conditions of an fMRI scan tend to progressively lull people into lower arousal states.

In the present study, the research team identified a specific blood flow signal that seemed to track both the decline in subject arousal levels and the illusory inflation of functional brain connection strengths.

This non-neuronal, physiological noise signal, termed the “systemic low frequency oscillation” (sLFO) signal, grew over time during scanning, in a spatial and temporal pattern that closely followed the pattern of the connection strength increases.

The researchers then demonstrated that a method called RIPTiDe, developed by co-senior author Blaise Frederick, PhD, an associate biophysicist at the McLean Imaging Center, to remove the sLFO signal from fMRI data, was able to eliminate the illusory connection strength increases.

“By adopting this sLFO denoising procedure, future studies can mitigate the distortive effects of arousal changes during brain scans and enhance the validity and reliability of fMRI findings,” said Korponay.

This research was supported by the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Institute on Aging, all part of the National Institutes of Health.

Source: Mass General Brigham McLean Hospital

Categories : CancerTags :

SAHPRA‘s Position on Anti-cancer Medications in South Africa

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Photo by Marcelo Leal on Unsplash

Pretoria, 15 July 2025 – The South African Health Products Regulatory Authority (SAHPRA) was notified of the Lancet Global Health 2025; 13: e1250, an investigational study and its findings on substandard anti-cancer medications in Sub-Saharan African countries, including Ethiopia, Kenya, Malawi, and Cameroon. This study did not include South Africa. The seven (7) medicines/dosage forms mentioned in the study are cisplatin, oxaliplatin, methotrexate, doxorubicin, cyclophosphamide, ifosfamide, and leucovorin. The specific brands mentioned/shown in the article are neither registered nor marketed in South Africa. 

SAHPRA, in terms of the Medicines and Related Substances Act 101 of 1965, as amended, and its General Regulations, requires medicines marketed in the country to meet prescribed requirements and adhere to set standards. Every batch of medicine produced must undergo testing to ensure that the integrity of the product is consistent with approved specifications before the release for sale, and imported medicines must additionally comply with the Guideline for Post-Importation Testing. 

SAHPRA commenced internal processes to verify whether any of the South African-registered cancer medicines with the mentioned Active Pharmaceutical Ingredients (API) might have been affected or implicated. The cancer products registered and marketed in South Africa were not implicated/affected by the investigational study and its findings on substandard anti-cancer medicines. SAHPRA conducts risk-based post-market surveillance (PMS), sampling, and testing on high-risk medical products. 

SAHPRA is satisfied that the marketed and registered cancer medicines meet the appropriate specifications; therefore, no substandard cancer medicines were detected. 

“SAHPRA is committed to the three pillars of quality, safety, and efficacy. I am satisfied that our rigorous regulatory processes have borne fruit and that all patients, especially cancer patients, can rest assured that their health and well-being are not compromised,” indicated SAHPRA CEO, Dr Boitumelo Semete-Makokotlela. 

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags :

Weekly Gel-based Injection for Parkinson’s Could Be a Game Changer

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A new weekly injectable drug could transform the lives of more than eight million people living with Parkinson’s disease, potentially replacing the need for multiple daily tablets.

UniSA PhD candidate Deepa Nakmode and Professor Sanjay Garg in the lab. Credit: UniSA

Scientists from the University of South Australia (UniSA) have developed a long-acting injectable formulation that delivers a steady dose of levodopa and carbidopa – two key medications for Parkinson’s – over an entire week.

Their findings have been reported in the journal Drug Delivery and Translational Research.

The biodegradable formulation is delivered in a subcutaneous or intramuscular injection, where it gradually releases the medication over seven days.

Parkinson’s disease is the second most common neurological disorder, affecting more than 8.5 million people worldwide. Currently there is no cure and the symptoms – tremors, rigidity and slow movement – are managed with oral medications that must be taken several times a day.

The frequent dosing is a burden, especially for elderly patients or those with swallowing difficulties, leading to inconsistent medication levels, more side effects, and reduced effectiveness.

Lead researcher Professor Sanjay Garg, from UniSA’s Centre for Pharmaceutical Innovation, says the newly developed injectable could significantly improve treatment outcomes and patient adherence.

“Our goal was to create a formulation that simplifies treatment, improves patient compliance, and maintains consistent therapeutic levels of medication. This weekly injection could be a game-changer for Parkinson’s care,” Prof Garg says.

“Levodopa is the gold-standard therapy for Parkinson’s, but its short life span means it must be taken several times a day.”

UniSA PhD student Deepa Nakmode says the in-situ implant is designed to release both levodopa and carbidopa steadily over one week, maintaining consistent plasma levels and reducing the risks associated with fluctuating drug concentrations.

“After years of focused research, it’s incredibly rewarding to see our innovation in long-acting injectables for Parkinson’s disease reach this stage. Our invention has now been filed for an Australian patent,” Nakmode says.

The injectable gel combines an FDA-approved biodegradable polymer PLGA with Eudragit L-100, a pH-sensitive polymer, to achieve a controlled and sustained drug release.

Extensive lab tests confirmed the system’s effectiveness and safety:

  • More than 90% of the levodopa dose and more than 81% of the carbidopa dose was released over seven days.
  • The implant degraded by over 80% within a week and showed no significant toxicity in cell viability tests.
  • The formulation can be easily administered through a fine 22-gauge needle, minimising discomfort and eliminating the need for surgical implant.

“The implications of this research are profound,” Prof Garg says. “By reducing the frequency of dosing from multiple times a day to a weekly injection is a major step forward in Parkinson’s therapy. We’re not just improving how the drug is delivered; we’re improving patients’ lives.”

Prof Garg says the technology could also be adapted for other chronic conditions such as cancer, diabetes, neurodegenerative disorders, pain management, and chronic infections that require long-term drug delivery.in

The system can be tuned to release drugs over a period ranging from a few days to several weeks depending on therapeutic needs.

UniSA scientists hope to start clinical trials in the near future and are exploring commercialisation opportunities.

Source: University of South Australia

Categories : Implants and Prostheses Metabolic DisordersTags :

Implantable Device Could Save Diabetes Patients from Dangerous Hypoglycaemia Episodes

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The new implant carries a reservoir of glucagon that can be stored under the skin and deployed during an emergency — with no injections needed.

Caption:A new implantable device carries a reservoir of glucagon that can be stored under the skin and could save diabetes patients from dangerously low blood sugar. Image: Courtesy of the researchers

Anne Trafton | MIT News

For people with Type 1 diabetes, developing hypoglycaemia, or low blood sugar, is an ever-present threat. When glucose levels become extremely low, it creates a life-threatening situation for which the standard treatment of care is injecting a hormone called glucagon.

As an emergency backup, for cases where patients may not realise that their blood sugar is dropping to dangerous levels, MIT engineers have designed an implantable reservoir that can remain under the skin and be triggered to release glucagon when blood sugar levels get too low.

This approach could also help in cases where hypoglycaemia occurs during sleep, or for diabetic children who are unable to administer injections on their own.

“This is a small, emergency-event device that can be placed under the skin, where it is ready to act if the patient’s blood sugar drops too low,” says Daniel Anderson, a professor in MIT’s Department of Chemical Engineering, a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science (IMES), and the senior author of the study. “Our goal was to build a device that is always ready to protect patients from low blood sugar. We think this can also help relieve the fear of hypoglycaemia that many patients, and their parents, suffer from.”

The researchers showed that this device could also be used to deliver emergency doses of epinephrine, a drug that is used to treat heart attacks and can also prevent severe allergic reactions, including anaphylactic shock.

Siddharth Krishnan, a former MIT research scientist who is now an assistant professor of electrical engineering at Stanford University, is the lead author of the study, which appears today in Nature Biomedical Engineering.

Emergency response

Most patients with type 1 diabetes use daily insulin injections to help their body absorb sugar and prevent their blood sugar levels from getting too high. However, if their blood sugar levels get too low, they develop hypoglycaemia, which can lead to confusion and seizures, and may be fatal if it goes untreated.

To combat hypoglycaemia, some patients carry preloaded syringes of glucagon, a hormone that stimulates the liver to release glucose into the bloodstream. However, it isn’t always easy for people, especially children, to know when they are becoming hypoglycaemic.

“Some patients can sense when they’re getting low blood sugar, and go eat something or give themselves glucagon,” Anderson says. “But some are unaware that they’re hypoglycaemic, and they can just slip into confusion and coma. This is also a problem when patients sleep, as they are reliant on glucose sensor alarms to wake them when sugar drops dangerously low.”

To make it easier to counteract hypoglycaemia, the MIT team set out to design an emergency device that could be triggered either by the person using it, or automatically by a sensor.

The device, which is about the size of a quarter, contains a small drug reservoir made of a 3D-printed polymer. The reservoir is sealed with a special material known as a shape-memory alloy, which can be programmed to change its shape when heated. In this case, the researcher used a nickel-titanium alloy that is programmed to curl from a flat slab into a U-shape when heated to 40 degrees Celsius.

Like many other protein or peptide drugs, glucagon tends to break down quickly, so the liquid form can’t be stored long-term in the body. Instead, the MIT team created a powdered version of the drug, which remains stable for much longer and stays in the reservoir until released.

Each device can carry either one or four doses of glucagon, and it also includes an antenna tuned to respond to a specific frequency in the radiofrequency range. That allows it to be remotely triggered to turn on a small electrical current, which is used to heat the shape-memory alloy. When the temperature reaches the 40-degree threshold, the slab bends into a U shape, releasing the contents of the reservoir.

Because the device can receive wireless signals, it could also be designed so that drug release is triggered by a glucose monitor when the wearer’s blood sugar drops below a certain level.

“One of the key features of this type of digital drug delivery system is that you can have it talk to sensors,” Krishnan says. “In this case, the continuous glucose-monitoring technology that a lot of patients use is something that would be easy for these types of devices to interface with.”

Reversing hypoglycaemia

After implanting the device in diabetic mice, the researchers used it to trigger glucagon release as the animals’ blood sugar levels were dropping. Within less than 10 minutes of activating the drug release, blood sugar levels began to level off, allowing them to remain within the normal range and avert hypoglycaemia.

The researchers also tested the device with a powdered version of epinephrine. They found that within 10 minutes of drug release, epinephrine levels in the bloodstream became elevated and heart rate increased.

In this study, the researchers kept the devices implanted for up to four weeks, but they now plan to see if they can extend that time up to at least a year.

“The idea is you would have enough doses that can provide this therapeutic rescue event over a significant period of time. We don’t know exactly what that is — maybe a year, maybe a few years, and we’re currently working on establishing what the optimal lifetime is. But then after that, it would need to be replaced,” Krishnan says.

Typically, when a medical device is implanted in the body, scar tissue develops around the device, which can interfere with its function. However, in this study, the researchers showed that even after fibrotic tissue formed around the implant, they were able to successfully trigger the drug release.

The researchers are now planning for additional animal studies and hope to begin testing the device in clinical trials within the next three years.

“It’s really exciting to see our team accomplish this, which I hope will someday help diabetic patients and could more broadly provide a new paradigm for delivering any emergency medicine,” says Robert Langer, the David H. Koch Institute Professor at MIT and an author of the paper.

Other authors of the paper include Laura O’Keeffe, Arnab Rudra, Derin Gumustop, Nima Khatib, Claudia Liu, Jiawei Yang, Athena Wang, Matthew Bochenek, Yen-Chun Lu, Suman Bose, and Kaelan Reed.

The research was funded by the Leona M. and Harry B. Helmsley Charitable Trust, the National Institutes of Health, a JDRF postdoctoral fellowship, and the National Institute of Biomedical Imaging and Bioengineering.

Reprinted with permission of MIT News