Beyond COVID to repurposing drugs and new gene-edited treatment options - here are our medical breakthroughs for 2023

Leigh Hart, one of our moderators and consultants looks at the impact of this year’s medical breakthroughs, from a drug to control obesity, to biomarkers for Parkinsons…

Though the 2023 Noble Prize for Physiology/Medicine went to the researchers whose work on nucleoside base modifications served as the base for developing effective mRNA vaccines against COVID-19, wider breakthroughs in the healthcare sector continue to move beyond the COVID-19 pandemic to encompass a broader range of issues.  This year’s breakthroughs, unfortunately, have less of a ‘wow’ factor than 2022’s breakthroughs (admittedly, it is very hard to top reviving dead pig organs), but alternatively they may have a more profound impact on global healthcare.

2023 Medical Breakthroughs

Semaglutide for Obesity

This year the diabetic drug Semaglutide (brand names Ozempic or Wegovy) was repurposed to target obesity. Though pilot trials for the drug’s use for obesity are only now underway, many physicians are already prescribing this drug off-license for obesity, at times leading to shortages.  Diabetes-related research had shown that it was possible to lose 15% of body mass when the drug was used as part of structured program. While semaglutide offers an important option for weight loss, it is not a panacea as its many side effects can have a considerable impact on quality of life.

“It is important to remember that obesity is heterogenous, chronic and complex. There is no one cure for obesity. It requires lifelong treatment that’s not one size fits all.’  Stated Vijaya Surampudi, MD, assistant director of the UCLA Weight Management Program (RFO).

First Gene-editing treatment approved - for Sickle Cell Anaemia

In a momentous move that finally realised the potential of gene-editing, this year both UK MHRA and US FDA licensed the first Crispr gene-editing treatment, Casgevy, for two inherited haemoglobin conditions - sickle cell anaemia and thalassemia. Gene-editing works by taking stem cells from a patient’s blood, editing the genetic code to disable the targeted faulty gene, and then reinserting the edited code back into the patient where it can then replicate normally and restore functionality.

"There are limited medicines currently available to Sickle Cell patients, so I welcome today's news that a new treatment has been judged safe and effective, which has the potential to significantly improve the quality of life for so many." John James OBE CEO of the sickle cell society

Fingertip secretion for Breast Cancer Screening?

While Chat GPT has introduced the world to the wider possibilities of machine learning, a small-scale machine learning study generated excitement in preventative care, as it may transform breast cancer screening.  Breast cancer is the most common cancer in women, but compliance with mammogram screening has been limited due to its discomfort, detection limitations and safety and cultural concerns. The recent Sheffield Hallam proof-of-concept study analysed fingerprint residue for breast cancer markers. Though small-scale, the study found that the combination of advanced spectrometry and machine learning was able to diagnose breast cancer with 97.8% accuracy.

Professor Francese stated: “This proof-of-concept study is at the interface of forensic science and clinical diagnostics and shows that fingerprints are valuable not only to obtain intelligence to profile criminal offenders but also to diagnose pathologies.”

Laboratory-based Biomarkers for Parkinson’s Disease

In a feeling not too dissimilar to waiting for a bus, this year two biomarkers were identified that could bring objective, laboratory-based rigor to the detection of Parkinson’s Disease (PD): α-synuclein in cerebral spinal fluid and a mitochondria DNA damage blood assay (mtDNA). The ability to diagnose PD early, and via an objective laboratory test rather than clinical assessment, will improve early PD diagnosis, better monitor PD progression, and better track response to treatment options.

‘Our hope is that our assay can not only diagnose Parkinson’s disease, but also identify drugs that reverse or halt mitochondrial DNA damage and the disease process. This disease takes a terrible toll on people, and we are still just treating the symptoms. It’s important to get new, effective treatments over the finish line.” states study leader Dr. Laurie Sanders.

Multiple Sclerosis Treatment Advances

Current Multiple Sclerosis (MS) treatments lose efficacy over time, potentially because they only focus on repairing the later stage damage to nerves and nerve sheaths. Two treatment advances published this year offer more hope. One study has found that injecting stem cells into the brain of patients with secondary MS halted their disease progression over the 12- month study period. Another study has shown that, in mice, myelin regeneration can result from targeting the inflamed and aggressive microglia with fractalkine. Additional hope is offered by the recently launched EU initiative to investigate the role that the Epstein-Barr virus (EBV) plays in triggering MS. It will look at all aspects of the link between the two diseases, including the underlying causation mechanisms, whether anti-virals can slow or halt MS disease course, and whether EMV vaccination offers benefits.

Professor Stefano Pluchino who led the stem cell study stated “We desperately need to develop new treatments for secondary progressive MS, and I am cautiously very excited about our findings, which are a step towards developing a cell therapy for treating MS.”

Severe Morning Sickness – Cause Identified

Most women experience nausea and vomiting in the first trimester of pregnancy. But those who develop the severe form, hyperemesis gravidarum (HG), can require hospitalisation to treat dehydration, nutritional insufficiency, low blood pressure, or a rapid heart rate. Until now, treatments only alleviated the symptoms of HG.  However, a recent study has shown that the levels of fetally-produced GDF15 in the mother’s blood, and maternal sensitivity to GDF15, underly whether the mother develops HG. This work is a first step towards addressing the underlying causes of the syndrome.

“If fetally-derived GDF15 is a primary driver of all nausea and vomiting during pregnancy, then that’s a big deal. It shows us a powerful way the fetal environment can use a single chemical signal to dramatically impact maternal health and behaviour.” said Professor Bart De Jonghe.

Long Covid – Detection and Anosmia Treatment

A recently developed MRI technique, called diffusion microstructure imaging (DMI), provides a means of mapping microstructural cerebral networks by studying the speed and direction of water molecules as they diffuse through tissue. Use of DMI on patients with and without long-COVID revealed that while cerebral macrostructures remained the same, those with long COVID had altered cerebral networks, revealing a previously hidden pathophysiological basis for the syndrome.

‘A better knowledge of long COVID-related underlying mechanisms is paramount, as it could be instrumental in guiding further research.’ Dr. Castanares-Zapatero stated.

Other work showed the people with anosmia (loss of smell) following COVID had reduced brain activity and impaired communication between the orbitofrontal cortex and the pre-frontal cortex. A potential treatment for anosmia and parosmia (altered sense of smell) following COVID may be the use of an anaesthetic/corticoid steroid injection as a stellate ganglion block, as research found that 60 % of patients reported improvements in their sense of smell after a week.

"Other treatments have failed to date; this injection is working." said Dr Zoga.

What to watch for in 2024

We believe that personalised care will continue to be a focus in healthcare. The recently issued Decentralised Clinical Trials (DCTs) Guidance stated that trials should seek to ‘strive’ towards diversity and inclusiveness in their trial populations, rather than be blind to factors such as sex, race and ethnic characteristics. More comprehensive collection and analysis of patient factors is the lynchpin for more personalised care.

We welcome that gender-specific issues, such as male depression and menopause, are now being discussed in mainstream media. More open and public discussions about such issues will not only promote awareness, but also drive research funding and priorities, and allow people to take an interest and ownership over their own health concerns.

We note that the healthcare impacts of greenhouse gases and associated climate change are now being elucidated, as highlighted by COP-28’s full day session devoted to discussing the impacts of climate change on healthcare. Indeed, recent estimates are that air pollution from fossil fuel burning killed more people in 2020 than COVID-19, with estimates of ~12 million deaths due to air pollution compared to ~3 million deaths due to COVID-19.

And we here at LDA Research are delighted that the recent map of the Rare Disease Landscape has highlighted that while £1.1 billion was invested in rare disease research from 2016-2021, over 49% of rare diseases receive no commercial backing. This is a great first step to better allocation of rare disease funding that will allow the UK to continue to be a thriving hub for cutting edge research.

“This report demonstrates the vibrant ecosystem for rare disease research that we have in the UK and underlines the importance of attracting industry to carry out clinical trials here” stated Janet Valentine, ABPI Director of Innovation and Research Policy.