A University of Queensland researcher has found molecular doorways that could be used to help deliver drugs into the brain to treat neurological disorders. Dr Rosemary Cater from UQ’s Institute for Molecular Bioscience led a team which discovered that an essential nutrient called choline is transported into the brain by a protein called FLVCR2.
“Choline is a vitamin-like nutrient that is essential for many important functions in the body, particularly for brain development,” Dr Cater said.
“We need to consume 400-500mg of choline per day to support cell regeneration, gene expression regulation, and for sending signals between neurons.”
Dr Cater said that until now, little was known about how dietary choline travels past the layer of specialised cells that separates the blood from the brain.
“This blood-brain barrier prevents molecules in the blood that are toxic to the brain from entering,” she explained. “The brain still needs to absorb nutrients from the blood, so the barrier contains specialised cellular machines – called transporters – that allow specific nutrients such as glucose, omega-3 fatty acids and choline to enter. While this barrier is an important line of defence, it presents a challenge for designing drugs to treat neurological disorders.”
Dr Cater was able to show that choline sits in a cavity of FLVCR2 as it travels across the blood-brain barrier and is kept in place by a cage of protein residues.
“We used high-powered cryo-electron microscopes to see exactly how choline binds to FLVCR2,” she said. “This is critical information for understanding how to design drugs that mimic choline so that they can be transported by FLVCR2 to reach their site of action within the brain. These findings will inform the future design of drugs for diseases such as Alzheimer’s and stroke.”
The research also highlights the importance of eating choline-rich foods – such as eggs, vegetables, meat, nuts and beans.
The research is published in Nature and funded by the National Institutes of Health.
After what was an insightful and collaborative meeting of the minds of healthcare professionals and experts at the 2024 BHF Annual Conference, the final day concluded by providing crucial insights into regulatory reforms shaping the future of healthcare in South Africa, as well as the legalities surrounding the controversial NHI Bill.
Facilitated by Nomo Khumalo, BHF Director and Head of Solutions at MMI Health, part one of the discussion comprised the key regulatory responses essential for building a resilient health system capable of navigating beyond current barriers.
Among the notable delegates participating in the discussion were Vincent Tlala, Registrar and CEO of the South African Pharmacy Council; Dr Magome Masike, Registrar of the Health Professions Council of South Africa; Dr Thandi S Mabeba, Chairperson of the Council for Medical Schemes; Dr Mark Blecher, Chief Director of Health and Social Development at the National Treasury; Yoliswa Makhasi, Director General of DPSA; and Dr Sandile Buthelezi, Director-General of the National Department of Health.
Their expertise across the healthcare regulatory sector added invaluable insights into the state of the sector, where they explored the current policy landscape, analysed the intent of reforms versus the realities, and discussed necessary changes for policymakers to ensure healthcare sustainability.
While all dignitaries note the need for Universal Health Coverage (UHC) to bridge the gap in access to healthcare in South Africa, Dr Sandile Buthelezi, acknowledged the complexity of implementing the NHI and the need for a phased approach. To this end, Buthelezi cited that significant work is required to establish the fund, develop regulations, and set up administrative structures.
“Apart from this, optimising healthcare delivery requires prioritising resource utilisation through proper management and spending, and addressing managerial issues to utilise available resources effectively,” suggests Buthelezi.
“Regulatory reforms are essential for advancing healthcare, encompassing standardised data collection, quality enhancement, and informed policy evolution. Moreover, the integration of digital health strategies is paramount, leveraging technology to bolster comprehensive health information systems and elevate healthcare delivery.”
Amidst the discussions, a common thread resonated among all dignitaries: the vital importance of collaboration. Here, Buthelezi stressed the necessity for stakeholders within the healthcare sector to unite in pursuit of shared goals, emphasising the need to improve health outcomes and effectively tackle challenges through collaborative efforts.
Following this, the conversation swung to the legalities of the impending NHI Bill in a session chaired by Michelle Beneke of Michelle Beneke Attorneys Inc, and featured industry experts Neil Kirby, Director at Werksmans Attorneys, and David Geral, Partner at Bowmans.
The conversation focused on the several facets of the implementation of the Bill, including its constitutionality, lack of government response to engagement efforts, and the broader regulatory challenges facing the healthcare industry.
According to Kirby, Werksman Attorneys, as legal representatives of BHF, have closely monitored the evolution of the NHI Bill, thoroughly scrutinising its alignment with South Africa’s constitutional principles.
“Regrettably, the implementation process hasn’t yielded a bill that adequately addresses our constitutional concerns. Despite incremental progress and assurances of future adjustments, the current iteration falls short of meeting the constitutional litmus test.
“As stakeholders directly impacted by the bill’s implications, we cannot afford to overlook constitutional shortcomings. Our obligation demands rigorous adherence to constitutional standards, ensuring that any legislation enacted upholds the rights and principles enshrined in our constitution,” he says.
To this end, Geral adds that the Bill introduces significant changes to the healthcare system, which may potentially affect tax policy and revenue sources.
In closing the conference, Dr Katlego Mothudi, Managing Director at BHF, emphasised the success of the conference in addressing industry challenges while promoting sustainability across the healthcare sector.
“As we conclude this enlightening conference, we reflect on the breadth of topics covered, from disease burden to the transformative potential of digitisation and AI in healthcare. Our discussions underscored the necessity of embracing change, combating fraud, and fostering regional collaboration.
“With a firm focus on healthcare reform, particularly the intricacies of the NHI Bill, our gathering has propelled us toward a future marked by innovation, resilience, sustainability and collective action. In the words of Edgar Tan – we can have what we need if we use what we have,” he concludes.
Researchers at MIT, Brigham and Women’s Hospital, and Harvard Medical School have developed a potential new treatment for alopecia areata, an autoimmune disorder that causes hair loss and affects people of all ages, including children.
For most patients with this type of hair loss, there is no effective treatment. The team developed a microneedle patch that can be painlessly applied to the scalp and releases drugs that help to rebalance the immune response at the site, halting the autoimmune attack.
In mice, this treatment allowed hair to regrow in mice and dramatically reduced inflammation at the treatment site, while avoiding systemic immune effects elsewhere in the body. This strategy could also be adapted to treat other autoimmune skin diseases such as vitiligo, atopic dermatitis, and psoriasis, the researchers say.
“This innovative approach marks a paradigm shift. Rather than suppressing the immune system, we’re now focusing on regulating it precisely at the site of antigen encounter to generate immune tolerance,” says Natalie Artzi, a principal research scientist in MIT’s Institute for Medical Engineering and Science, an associate professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, and an associate faculty member at the Wyss Institute of Harvard University.
Artzi and Jamil R. Azzi, an associate professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, are the senior authors of the new study, which appears in the journal Advanced Materials. Nour Younis, a Brigham and Women’s postdoc, and Nuria Puigmal, a Brigham and Women’s postdoc and former MIT research affiliate, are the lead authors of the paper.
The researchers are now working on launching a company to further develop the technology, led by Puigmal, who was recently awarded a Harvard Business School Blavatnik Fellowship.
Targeted delivery
Alopecia areata occurs when the body’s own T cells attack hair follicles, leading the hair to fall out. The only treatment available to most patients – injections of immunosuppressant steroids into the scalp – is painful and patients often can’t tolerate it.
Some patients with alopecia areata and other autoimmune skin diseases can also be treated with immunosuppressant drugs that are given orally, but these drugs lead to widespread suppression of the immune system, which can have adverse side effects.
“This approach silences the entire immune system, offering relief from inflammation symptoms but leading to frequent recurrences. Moreover, it increases susceptibility to infections, cardiovascular diseases, and cancer,” Artzi says.
A few years ago, at a working group meeting in Washington, Artzi happened to be seated next to Azzi (the seating was alphabetical), an immunologist and transplant physican who was seeking new ways to deliver drugs directly to the skin to treat skin-related diseases.
Their conversation led to a new collaboration, and the two labs joined forces to work on a microneedle patch to deliver drugs to the skin. In 2021, they reported that such a patch can be used to prevent rejection following skin transplant. In the new study, they began applying this approach to autoimmune skin disorders.
“The skin is the only organ in our body that we can see and touch, and yet when it comes to drug delivery to the skin, we revert to systemic administration. We saw great potential in utilising the microneedle patch to reprogram the immune system locally,” Azzi says.
The microneedle patches used in this study are made from hyaluronic acid crosslinked with polyethylene glycol (PEG), both of which are biocompatible and commonly used in medical applications. With this delivery method, drugs can pass through the tough outer layer of the epidermis, which can’t be penetrated by creams applied to the skin.
“This polymer formulation allows us to create highly durable needles capable of effectively penetrating the skin. Additionally, it gives us the flexibility to incorporate any desired drug,” Artzi says. For this study, the researchers loaded the patches with a combination of the cytokines IL-2 and CCL-22. Together, these immune molecules help to recruit T reg cells, which proliferate and help to tamp down inflammation. These cells also help the immune system learn to recognise that hair follicles are not foreign antigens, so that it will stop attacking them.
Hair regrowth
The researchers found that mice treated with this patch every other day for three weeks had many more T reg cells present at the site, along with a reduction in inflammation. Hair was able to regrow at those sites, and this growth was maintained for several weeks after the treatment ended. In these mice, there were no changes in the levels of T reg cells in the spleen or lymph nodes, suggesting that the treatment affected only the site where the patch was applied.
In another set of experiments, the researchers grafted human skin onto mice with a humanised immune system. In these mice, the microneedle treatment also induced proliferation of T reg cells and a reduction in inflammation.
The researchers designed the microneedle patches so that after releasing their drug payload, they can also collect samples that could be used to monitor the progress of the treatment. Hyaluronic acid causes the needles to swell about tenfold after entering the skin, which allows them to absorb interstitial fluid containing biomolecules and immune cells from the skin.
Following patch removal, researchers can analyse samples to measure levels of T reg cells and inflammation markers. This could prove valuable for monitoring future patients who may undergo this treatment.
The researchers now plan to further develop this approach for treating alopecia, and to expand into other autoimmune skin diseases.
The healthcare sector in South Africa is beset with numerous challenges, ranging from high turnover rates to skilled staffing shortages and complex regulations in addition to stressful working environments, and communication barriers.
Despite these formidable obstacles, patients have the right to expect top-tier care from their medical facilities. Here, specialised Temporary Employment Services (TES) providers can become indispensable partners, adeptly assisting medical facilities to navigate these challenges in their quest to ensure a seamless continuum of care.
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