Publications

Publication: Annals of the New York Academy of Sciences

Kerry S. Jones, Damon A. Parkington, Lorna J. Cox, Albert Koulman

22 December 2020

Summary:

Vitamin B1 (thiamine) is an essential nutrient required for energy metabolism and the nervous system.  Thiamine deficiency can cause infantile beriberi (a potential life-threatening condition that affects multiple parts of the body.) Populations particularly at risk of thiamine deficiency are breastfed infants of thiamine-deficient mothers in low-income countries, especially those where rice, which contains little thiamine, is the staple food. However, deficiency is associated with a range of non-specific clinical symptoms and can be difficult to diagnose. Evidence also exists to suggest that mild thiamine deficiency may have long-term effects on brain development and gross motor skills.

Biomarkers are compounds we can measure in blood that tell us about a person’s physiology and health. Biomarkers of thiamine status are essential to identify deficiency and improve understanding of the global prevalence of thiamine deficiency and of the links between thiamine and later health outcomes.

An important biomarker of thiamine status is the “erythrocyte transketolase activity coefficient” (ETKAC). ETKAC is a measure of the availability of thiamine available for use in in red blood cells (erythrocytes).

Researchers provided a step-by-step protocol to perform the ETKAC assay. It will facilitate harmonisation of the ETKAC assay. It provides a foundation for the establishment of the assay in new laboratories and supports the investigation of outstanding questions in thiamine biology contributing to the ultimate aim of developing strategies to control thiamine deficiency.

Publication: AHA Stroke

Kathrine J. Vinknes, Helga Refsum, Cheryl Turner, Kay-Tee Khaw, Nicholas J. Wareham, Nita G. Forouhi, Fumiaki Imamura

22 December 2020

B-vitamin supplements lower circulating concentrations of homocysteine and may reduce stroke incidence. Homocysteine concentrations are associated with the incidence of stroke but other sulfur-containing compounds in the related metabolic pathway have not yet been investigated for an association with incident cerebrovascular diseases.

Nested within the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Norfolk cohort, we established a case-control study with 480 incident cases of cerebrovascular diseases and 480 controls matched by age, sex, and year of baseline examination (1993–1997).

Using baseline plasma samples, we assayed sulfur-containing compounds including methionine, homocysteine, cystathionine, cysteine, glutathione, and taurine with liquid chromatography–tandem mass spectrometry. We examined the association of concentrations of each of the compounds and the ratio of methionine to homocysteine (representing activity of one-carbon metabolism) with risk of incident cerebrovascular diseases, adjusted for potential confounders.

Plasma methionine and the methionine/homocysteine ratio were inversely associated with risk of cerebrovascular diseases, with odds ratios per 1 SD of 0.83 and 0.82, respectively. The association of methionine remained significant after adjustment for homocysteine. None of the other examined compounds was significantly associated with incident cerebrovascular diseases.

Conclusions: These findings suggest that greater availability of methionine, an essential amino acid, may play a role in the prevention of cerebrovascular diseases and explain the previously recognized link between elevated homocysteine and stroke. Further research is needed to determine causation and the potential of circulating methionine as a target in cerebrovascular disease prevention.

Publication: Transfusion Medicine

Steven Bell, Michael Sweeting, Anna Ramond, Ryan Chung, Stephen Kaptoge, Matthew Walker, Thomas Bolton, Jennifer Sambrook, Carmel Moore, Amy McMahon, Sarah Fahle

20 December 2020

To safeguard donors, blood services measure haemoglobin concentration in advance of each donation. NHS Blood and Transplant’s (NHSBT) customary method have been capillary gravimetry (copper sulphate), followed by venous spectrophotometry (HemoCue) for donors failing gravimetry. However, NHSBT’s customary method results in 10% of donors being inappropriately bled (ie, with haemoglobin values below the regulatory threshold).

Here the researchers compared the following four methods in 21 840 blood donors (aged ≥18 years) recruited from 10 NHSBT centres in England, with the Sysmex XN‐2000 haematology analyser, the reference standard: (1) NHSBT’s customary method; (2) “post donation” approach, that is, estimating current haemoglobin concentration from that measured by a haematology analyser at a donor’s most recent prior donation; (3) “portable haemoglobinometry” (using capillary HemoCue); (4) non‐invasive spectrometry (using MBR Haemospect or Orsense NMB200). The team assessed sensitivity; specificity; proportion who would have been inappropriately bled, or rejected from donation (“deferred”) incorrectly; and test preference.

Compared with the reference standard, the methods ranged in test sensitivity from 17.0% (MBR Haemospect) to 79.0% (portable haemoglobinometry) in men, and from 19.0% (MBR Haemospect) to 82.8% (portable haemoglobinometry) in women.

For specificity, the methods ranged from 87.2% (MBR Haemospect) to 99.9% (NHSBT’s customary method) in men, and from 74.1% (Orsense NMB200) to 99.8% (NHSBT’s customary method) in women. The proportion of donors who would have been inappropriately bled ranged from 2.2% in men for portable haemoglobinometry to 18.9% in women for MBR Haemospect. The proportion of donors who would have been deferred incorrectly with haemoglobin concentration above the minimum threshold ranged from 0.1% in men for NHSBT’s customary method to 20.3% in women for OrSense. Most donors preferred non‐invasive spectrometry.

In the largest study reporting head‐to‐head comparisons of four methods to measure haemoglobin prior to blood donation, the results support replacement of NHSBT’s customary method with portable haemoglobinometry.

Publication: New England Journal of Medicine

Peter J. Hutchinson, Ellie Edlmann, Diederik Bulters, Ardalan Zolnourian, Patrick Holton, Nigel Suttner,  Kevin Agyemang, Simon Thomson, Ian A. Anderson, Yahia Z. Al-Tamimi, Duncan Henderson, Peter C. Whitfield, Monica Gherle, Paul M. Brennan, Annabel Allison,  Eric P. Thelin, Silvia Tarantino, Beatrice Pantaleo, Karen Caldwell, Carol Davis-Wilkie, Harry Mee, Elizabeth A. Warburton, Garry Barton, Aswin Chari, Hani J. Marcus, Andrew T. King, Antonio Belli, Phyo K. Myint, Ian Wilkinson, Thomas Santarius, Carole Turner,  Simon Bond, Angelos G. Kolias,

16 December 2020

Summary:

Chronic subdural haematoma -the build-up of ‘old’ blood in the space between the brain and the skull, usually as a result of minor head injury – is one of the most common neurological disorders and mainly affects older people.

A commonly used steroid, dexamethasone, has been used alongside surgery or instead of it since the 1970s. However, consensus has been lacking regarding the use of dexamethasone, especially since no high-quality studies confirming its effectiveness had been conducted until now.

In a randomised trial, patients received a two-week tapering course of dexamethasone and were compared with 373 patients randomised to an identical matching placebo. Results showed patients who received dexamethasone had a lower chance of favourable recovery at six months compared to patients who received placebo. Read the full press release. 

Publication: Journal of Clinical Densitometry

Watson, L., Carr, K., Orford, E. and Venables, M.

15 December 2020

Body composition is associated with many noncommunicable diseases.

The accuracy of many simple techniques used for the assessment of body composition is influenced by the fact that they do not take into account tissue hydration and this can be particularly problematic in paediatric populations.

This study looked at DXA systems for determining total and regional (arms, legs, trunk) fat, lean, and bone mass and compared lean soft tissue (LST) hydration correction methods in 124 children aged between 6 and 16 years old.

The study showed that care needs to be exercised when combining data from iDXA and Prodigy, as total and regional estimates of body composition can differ significantly.

Furthermore, tissue hydration should be taken into account when assessing body composition as it can vary considerably within a healthy paediatric population even within specific age and/or sex groups.

Publication: Alzheimer's & Dementia: The Journal of the Alzheimer's Association

Maura Malpetti, P. Simon Jones, Kamen A. Tsvetanov, Timothy Rittman, John C. van Swieten, Barbara Borroni, Raquel Sanchez‐Valle, Fermin Moreno, Robert Laforce, Caroline Graff, Matthis Synofzik, Daniela Galimberti, Mario Masellis, Maria Carmela Tartaglia, Elizabeth Finger, Rik Vandenberghe, Alexandre de Mendonça, Fabrizio Tagliavini Isabel Santana, Simon Ducharme, Chris R. Butler, Alexander Gerhard, Johannes Levin, Adrian Danek, Markus Otto,Giovanni B. Frisoni, Roberta Ghidoni, Sandro Sorbi,Carolin Heller,Emily G. Todd, Martina Bocchetta, David M. Cash,Rhian S. Convery, Georgia Peakman, Katrina M. Moore, Jonathan D. Rohrer, Rogier A. Kievit, James B. Rowe

15 December 2020

Summary:

Apathy – a lack of interest or motivation – could predict the onset of some forms of dementia many years before symptoms start, offering a ‘window of opportunity’ to treat the disease at an early stage. Apathy changes decades before dementia onset and is driven by early brain shrinkage in individuals at risk of dementia. Early signs of apathy before dementia predict a faster decline in cognitive performance. Apathy can point to early brain changes even years before dementia symptoms begin, providing a window of opportunity to intervene and slow disease progression. Read the full news story.

Publication: Current Biology

Camilla L. Nord, Edwin S. Dalmaijer, Thomas Armstrong, Kate Baker, Tim Dalgleish

24 November 2020

Summary:

Disgust is a natural response to unpleasant sights, but for some people, disgust can become pathological, affecting their mental health and quality of life.

Researchers have shown that domperidone, a commonly-prescribed anti-nausea medicine, can help significantly reduce how much volunteers look away from disgusting images. Read the full news story.

Publication: Frontiers in Psychiatry

Chen S, She R, Qin P, Kershenbaum A, Fernández-Egea E, Nelder JR, Ma C, Lewis JR, Wang C, Cardinal RN

26 November 2020

To date, there is a paucity of information regarding the effect of COVID-19 or lockdown on mental disorders.

In this study researchers aimed to quantify the medium-term impact of lockdown on referrals to secondary care mental health clinical services.

They conducted a controlled interrupted time series study using data from Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), UK (catchment population ~0.86 million).

The UK lockdown resulted in an instantaneous drop in mental health referrals but then a longer-term acceleration in the referral rate. This acceleration was primarily for urgent or emergency referrals, including referrals to liaison psychiatry and mental health crisis teams. The acceleration was significant for females, males, working-age adults, people of White ethnicity, those living alone, and those who had pre-existing depression, severe mental illness, hypertension / cardiovascular / cerebrovascular disease, personality disorders, asthma / chronic obstructive pulmonary disease, dyslipidemia, anxiety, substance misuse or reactions to severe stress.

No significant post-lockdown acceleration was observed for children / adolescents, older adults, people of ethnic minorities, married / cohabiting people, and those who had previous / pre-existing dementia, diabetes, cancer, eating disorder, a history of self-harm or intellectual disability. This evidence may help service planning and policy-making, including preparation for any future lockdown in response to outbreaks.

Publication: European Neuropsychopharmacology

J.R. Breedon, H. Ziauddeen, J. Stochl, K.D. Ersche

24 November 2020

This research investigates the underlying mechanism of addictive behaviour as exemplified by cocaine addiction, and how it impacts on other behaviours such as eating.

Cocaine is adept at being both highly pleasurable and highly habit-forming and both processes are involved in the development of addiction. But are these behavioural changes specific to just cocaine consumption or do they impact other behaviours? This is an interesting question because food consumption is a paradigmatic example of behaviour that can be dominated by both deliberate (so-called goal-directed) and habitual control. As an example, people on diets will exert a high degree of control over their calorific and nutritional intake (‘goal directed’) only to find themselves falling back into old patterns of eating (‘habits’). This is an important question to ask because what we eat has clear and direct consequences for our health; if cocaine addiction has detrimental implications for food consumption, this will have health consequences, beyond the direct consequence of cocaine use.

The researchers presented participants with pictures of food and asked them to rate how much they were willing to pay for them, and how much they wanted to eat the foods. In addition they used questionnaires to investigate both the reasons why cocaine-addicted individuals use cocaine, and the factors influencing their food-related choices.

The results suggest that cocaine addiction narrows the goals of individuals away from ‘normal’ motivators like food, and diverts it towards cocaine. Further, the results suggest that food behaviour in cocaine addiction is more habitual, supporting the hypothesis that the habits developed are wide-reaching and affect behaviours beyond cocaine.

These results will be of interest to those working with individuals with cocaine addiction – they suggest that more attention should be paid to the eating habits of those affected. Further they add support for the ‘habit theory’ of addiction, and suggest that further research into treatments for cocaine addiction should consider the possibility of habits training, that is, methods of directing this ‘habit bias’ towards healthier, more meaningful, activities.

Publication: Cancers

Contributing NIHR Cambridge BRC researchers: Andrew B Gill, Leonardo Rundo, Jonathan C. M. Wan, Doreen Lau, Jeries P. Zawaideh, Ramona Woitek, Fulvio Zaccagna, Lucian Beer, Davina Gale, Evis Sala, Dominique-Laurent Couturier, Pippa G. Corrie, Nitzan Rosenfeld and Ferdia A. Gallagher

24 November 2020

The analysis of circulating tumor DNA (ctDNA) concentrations in blood plasma and the radiomic analysis of tumor images (i.e., quantification of textural features on medical imaging) have both been used to provide information about cancer progression. The purpose of this study was to assess a link between these two different modalities in order to determine whether results from one can be used to predict outcomes from the other.

The results show that radiomics features can predict ctDNA levels in patients with metastatic melanoma even when controlling for other factors such as tumor volume.

This establishes the potential for new biomarkers of tumor progression that could combine the specificity of ctDNA assays with the high-resolution spatial information obtained by imaging. This could enable more accurate assessment of tumor response to treatment and provide clinicians with more timely indications of whether a particular therapeutic option is working or not.

Publication: Nature Genetics

Praveen Surendran, Joanna M. M. Howson et al

23 November 2020

Increased blood pressure (BP) is a major risk factor for cardiovascular disease (CVD) and related disability worldwide. Identifying biological pathways associated with blood pressure is important to understand the aetiology of CVD.

In this study involving collaborators from across the globe, and participants from diverse ancestries, researchers investigated whether genetic variants that a small proportion of people carry have an impact on blood pressure regulation and more readily implicate the genes underlying blood pressure regulation.

They identified 87 such genetic variants influencing blood pressure regulation that only a small proportion of people carry. In addition to identifying novel candidate genes associated with blood pressure, they showed a potential link between foetal development and an inverse relationship between systolic and diastolic blood pressure with stroke.

As shown in this study, a complex outcome like blood pressure requires large sample sizes to detect genetic variation associated with blood pressure that are rare in humans; studies to date have mainly looked at genetic variants that are carried by many people and therefore have very small effects on blood pressure regulation.

This study contributes to a significant improvement in researchers’ understanding of key genes controlling a risk factor like BP so they can better understand complex diseases like CVD and help identify new blood pressure therapies.

Publication: Alzheimer's and Dementia

Kamen A. Tsvetanov, Stefano Gazzina, P. Simon Jones, John van Swieten, Barbara Borroni, Raquel Sanchez‐Valle, Fermin Moreno, James B. Rowe et al

20 November 2020

The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. The research team investigate this phenomenon in familial frontotemporal dementia (FTD).

There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, the researchers identified behaviorally relevant structural and functional network differences. Structure‐function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non‐carriers, and increased with proximity to the expected onset of disease.

The findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance.

Publication: Diabetes Care

Ju-Sheng Zheng, Jian’an Luan, Eleni Sofianopoulou, Fumiaki Imamura, Isobel D. Stewart, Felix R. Day, Maik Pietzner, Eleanor Wheeler, Luca A. Lotta, Thomas E. Gundersen, Pilar Amiano, Eva Ardanaz, María-Dolores Chirlaque, Guy Fagherazzi, Paul W. Franks, Rudolf Kaaks, Nasser Laouali, Francesca Romana Mancini, Peter M. Nilsson, N. Charlotte Onland-Moret, Anja Olsen, Kim Overvad, Salvatore Panico, Domenico Palli, Fulvio Ricceri, Olov Rolandsson, Annemieke M.W. Spijkerman, María-José Sánchez, Matthias B. Schulze, Núria Sala, Sabina Sieri, Anne Tjønneland, Rosario Tumino, Yvonne T. van der Schouw, Elisabete Weiderpass, Elio Riboli, John Danesh, Adam S. Butterworth, Stephen J. Sharp, Claudia Langenberg, Nita G. Forouhi, Nicholas J. Wareham

17 November 2020

Summary:

Type 2 is a condition with serious health problems. Previous research has shown higher blood levels of vitamin C were linked with lower future risk of type 2 diabetes and if this was proven, it could mean that giving vitamin C as a supplement may help in preventing the condition. Testing this theory is quite challenging due to finding the correct dose.

Researchers identified 11 genetic markers that can predict blood levels of vitamin C using a large sample of more than 50,000 adults. They tested the association of type 2 diabetes with genetically predicted vitamin C levels with a large sample size of more than 80,000 people with diabetes and up-to 840,000 people without diabetes.

They found a mismatch when comparing the link of diabetes with the genetically predicted vitamin C levels versus when used directly measured blood vitamin C levels. The researchers results for directly measured or genetically predicted blood vitamin C levels indicated that blood vitamin C is not likely to be a causal factor for the development of type diabetes. Therefore conclude that it is not justified to use vitamin C supplementation for the prevention of type 2 diabetes.

Researchers highlighted that the current research findings should be interpreted as showing no link of the micronutrient vitamin C with type 2 diabetes.

Publication: Neurobiology of Aging

Elijah Mak, Nicolas Nicastro, Maura Malpetti, George Savulich, Ajenthan Surendranathan, Negin Holland, Luca Passamonti, Simon P. Jones, Stephen F. Carter, Li Su Young T.Hong, Tim D.Fryer, Guy B. Williams, Franklin Aigbirhio, James B. Rowe & John T. O’Brien

14 November 2020

Alzheimer’s disease (AD) pathology is frequently observed as a comorbidity in people with dementia with Lewy bodies (DLB). Here, the research team evaluated the in vivo distribution of tau burden and its influence on the clinical phenotype of DLB.

Tau deposition was quantified using [18F]-AV1451 positron emission tomography in people with DLB (n = 11) and AD (n = 27), and healthy controls (n = 14). A subset of subjects with Lewy body diseases (n = 4) also underwent [11C]-PK11195 PET to estimate microglial activation. [18F]-AV1451 BPND was lower in DLB compared to AD across widespread regions. The medial temporal lobe [18F]-AV1451 BPND distinguished people with DLB from AD (AUC = 0.87), and negatively correlated with ACE-R and MMSE. There was a high degree of colocalisation between [18F]-AV1451 and [11C]-PK11195 binding (p<0.001).

The findings of minimal tau burden in DLB confirm previous studies. Nevertheless, the associations of [18F]-AV1451 binding with cognitive impairment, suggest that tau may interact synergistically with other pathological processes to aggravate disease severity in DLB.

Publication: BMJ

Ranya Mulchandani, Hayley E Jones, Sian Taylor-Phillips, Justin Shute, Keith Perry, Shabnam Jamarani, Tim Brooks, Andre Charlett, Matthew Hickman, Isabel Oliver, Stephen Kaptoge, John Danesh, Emanuele Di Angelantonio, Anthony E Ades, David H Wyllie, 

11 November 2020

Summary:

The accuracy of a COVID-19 test is lower than previously believed. Testing nearly 5,000 samples found some results were giving false positives.

Publication: Journal of Neurology, Neurosurgery, and Psychiatry

Maura Malpetti, Timothy Rittman, Peter Simon Jones, Thomas Edmund Cope, Luca Passamonti, William Richard Bevan-Jones, Karalyn Patterson, Tim D Fryer, Young T Hong, Franklin I Aigbirhio, John Tiernan O’Brien, James Benedict Rowe

29 October 2020

Summary:

Using PET imaging, researchers looked at neuro inflammation and abnormal growth of protein for patients with frontotemporal dementia (FTD). They found Familial FTD was associated with neuroinflammation across all genes and also reflected clinical heterogeneity. This research will be able to help to further understand the disease and in particular around the immune system to help with treatments and prevention.

Publication: International Journal of Geriatric Psychiatry

Kershenbaum A, Cardinal RN, Chen S, Underwood B, Seyedsalehi A, Lewis JR, Rubinsztein JS

4 November 2020

Previous studies have shown increased rates of death and dementia in older people in specific serious mental illnesses (SMI) such as bipolar disorder or depression.

In this study researchers examined the rates of death and dementia in older people referred into a secondary care psychiatric service across a range of SMIs, using an anonymised dataset across 6 consecutive years with 28,340 patients aged 65 years and older from a single secondary care psychiatric trust in the United Kingdom.

They identified deaths and incident dementia in patients with bipolar disorder/mania, schizophrenia, recurrent depression and anxiety disorders. They compared mortality and dementia rates between these diagnostic groups and in different treatment settings, and also examined mortality rates and dementia rates compared with general population rates.

Patients with schizophrenia showed the highest hazard rate for death compared to other groups with SMIs. Survival was reduced in patients referred to liaison psychiatry services. There were no significant differences between the SMI groups in terms of rates of dementia. However, risks of death and dementia were significantly increased compared to the general population; and older adults referred into an old age psychiatry service showed higher rates of dementia and death than those reported for the general population.

Publication: Brain A Journal of Neurology

Alexander G Murley, Matthew A Rouse, P Simon Jones, Rong Ye, Frank H Hezemans, Claire O’Callaghan, Polytimi Frangou, Zoe Kourtzi, Catarina Rua, T Adrian Carpenter, Christopher T Rodgers, James B Rowe

3 November 2020

Behavioural disinhibition is a common feature of the syndromes associated with frontotemporal lobar degeneration (FTLD). It is associated with high morbidity and lacks proven symptomatic treatments. A potential therapeutic strategy is to correct the neurotransmitter deficits associated with FTLD, thereby improving behaviour. Reductions in the neurotransmitters glutamate and GABA correlate with impulsive behaviour in several neuropsychiatric diseases and there is post-mortem evidence of their deficit in FTLD. Here, the researchers tested the hypothesis that prefrontal glutamate and GABA levels are reduced by FTLD in vivo, and that their deficit is associated with impaired response inhibition.

They measured glutamate and GABA levels using semi-LASER magnetic resonance spectroscopy in the right inferior frontal gyrus, because of its strong association with response inhibition, and in the primary visual cortex, as a control region. The stop-signal reaction time was calculated using an ex-Gaussian Bayesian model. Participants with frontotemporal dementia and progressive supranuclear palsy had impaired response inhibition, with longer stop-signal reaction times compared with controls. GABA concentration was reduced in patients versus controls in the right inferior frontal gyrus, but not the occipital lobe. There was no group-wise difference in partial volume corrected glutamate concentration between patients and controls. Both GABA and glutamate concentrations in the inferior frontal gyrus correlated inversely with stop-signal reaction time, indicating greater impulsivity in proportion to the loss of each neurotransmitter.

The researchers conclude that the glutamatergic and GABAergic deficits in the frontal lobe are potential targets for symptomatic drug treatment of frontotemporal dementia and progressive supranuclear palsy.

Publication: ACL Anthology

Wang Z, Ive J, Moylett S, Mueller C, Cardinal RN, Velupillai S, O’Brien J, Stewart R

1 November 2020

While Dementia with Lewy Bodies (DLB) is the second most common type of neurodegenerative dementia following Alzheimer’s Disease (AD), it is difficult to distinguish from AD.

Here the researchers propose a method for DLB detection by using mental health record (MHR) documents from a (3-month) period before a patient has been diagnosed with DLB or AD. The objective is to develop a model that could be clinically useful to differentiate between DLB and AD across datasets from different healthcare institutions.

The researchers cast this as a classification task using Convolutional Neural Network (CNN), an efficient neural model for text classification. They experiment with different representation models, and explore the features that contribute to model performances.

In addition, they apply temperature scaling, a simple but efficient model calibration method, to produce more reliable predictions. They believe the proposed method has important potential for clinical applications using routine healthcare records, and for generalising to other relevant clinical record datasets.

To the best of the team’s knowledge, this is the first attempt to distinguish DLB from AD using mental health records, and to improve the reliability of DLB predictions.

Publication: The Lancet: Diabetes and Endocrinology

Prof Karine Clément, MD, Prof Erica van den Akker, MD, Prof Jesús Argente, MD, Allison Bahm, MD, Prof Wendy K Chung, MD, Hillori Connors, MS, Kathleen De Waele, MD, Prof I Sadaf Farooqi, PhD, Julie Gonneau-Lejeune, MD, Gregory Gordon, MD, Katja Kohlsdorf, MD, Prof Christine Poitou, MD, Lia Puder, MD, James Swain, MD, Murray Stewart, DM, Guojun Yuan, PhD, Prof Martin Wabitsch, MD, Prof Peter Kühnen, MD

30 October 2020

Summary:

In this international phase 3 study, researchers wanted to see if the drug Setmelanotide could help people whose severe obesity is caused by pro-opiomelanocortin (POMC) or leptin (LEPR) deficiency.

Melanocortin 4 Receptor (MC4R), plays a critical part in bodyweight regulation and Setmelanotide is an MC4R agonist. This trial was conducted in several countries with participants with severe obesity due to either POMC deficiency LEPR deficiency.

After approximately 1 year, eight (80%) participants in the POMC trial and five (45%) participants in the LEPR trial achieved at least 10% weight loss. Researchers found Setmelanotide to be a safe and effective treatment for people with POMC or LEPR deficiency.

This research could benefit people who find it hard to lose weight. There are ongoing trials to test whether Setmelanotide is effective in other genetic obesity syndromes.