Research Projects

PI: Professor Dan Stein

The immediate, specific aims of the ABHGP pilot data registry are to:
1) Draw on the resources of the different components of the Neuroscience Institute (NI), including Neurology, Neurosurgery, and Psychiatry, and develop an integrated protocol for collaborating on a shared neuroscience resource.
2) Establish approaches to database design, subject recruitment, genotyping, and phenotyping.
3) Study aspects of phenotyping and genotyping in relation to adolescents with mental and substance use disorder, adolescents and adults with seizure disorder, and adolescents and adults with TBI, as specified in more detail in the next section.

3 branches of the study:
Seizure Disorder:
A target of 200 adult and 50 adolescent participants suffering from epilepsy or seizure disorders (125 formally diagnosed with either focal or generalized epilepsy and 125 with psychogenic non-epileptic seizures (PNES)) will be recruited from Groote Schuur Hospital, Clinical Neurology Unit, and followed up at 12 months. 100 adult matched healthy controls will also be recruited.
Traumatic Brain Injury:
200 adult and 50 adolescent participants will be recruited from Groote Schuur Hospital, Trauma Unit and/or Neurosurgery Ward and followed up at 12 months. 100 adult matched healthy controls will also be recruited.
Adolescents (internalizing disorders):
A sub sample of 200 adolescents (recruited from surrounding schools), healthy controls and those with internalizing disorders, will be invited for neuroimaging.

PI: Professor Chris Scott

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely disabling, congenital genetic disease characterized by progressive multi-focal heterotopic ossification (HO) of skeletal muscle, ligaments, tendons, and fascia. Heterotopic ossification is the abnormal growth of bone in non-skeletal tissues. FOP is estimated to occur in approximately 1 in 0.63 to 1.86 million individuals based on reports of diagnosed cases. This is a phase 3, randomized, multi-center, multinational, parallel-group, placebo-controlled study to assess the efficacy of garetosmab on the reduction of heterotopic bone formation, and its safety, tolerability, and PK in FOP patients with active disease caused by any FOP-causing variant of ACVR1.

PI: Professor Ernesta Meintjes, A/Professor Andre van der Kouwe, Professor Sandra W. Jacobson & Professor R. Colin Carter

Fetal alcohol spectrum disorders (FASD) represent the most prevalent cause of preventable intellectual disability worldwide. Prenatal alcohol exposure (PAE) impacts the developing brain, resulting in cognitive deficits, growth restriction and structural brain changes. Despite psychosocial interventions, heavy drinking during pregnancy continues to be a major public health challenge globally.
We are conducting a fully-powered, double-blind, placebo-controlled randomized clinical trial (RCT) of maternal micronutrient supplementation (called the MOMS Study) in rural areas around Cape Town where the prevalence of heavy drinking during pregnancy is high. As part of MOMS, 288 heavy drinking women will be given choline or placebo during pregnancy, and infants will be assessed through 12 months of age.
The BAMBI neuroimaging sub-study will take advantage of the unique opportunity afforded by the MOMS RCT to conduct high- and low-field neuroimaging in infants born to choline- and placebo-treated mothers within the 1st postnatal month and again at age 12 months to identify neuroimaging markers of maternal choline supplementation in infants with PAE. MR protocols will include brain anatomical, diffusion and metabolic spectral imaging. Our central hypothesis is that choline supplementation in heavy drinking pregnant women will reduce the adverse impact of PAE on the developing fetal and infant brain by normalizing anatomical development, connectivity and brain metabolism. To test this hypothesis, we will combine the clinical and nutritional information and infant cognitive test results from MOMS with the brain anatomical, connectivity and metabolic measurements from the current study in a longitudinal analysis to elucidate mechanistic underpinnings of the neuroprotective benefits of prenatal maternal choline supplementation on the developing fetus. We will also assess how sensitive low-field, accessible MRI is to detecting the outcomes measured with 3T MRI.

PI: Dr Sameera Dalvie

Melanoma is cancer affecting the pigment producing cells of the body.
The primary objective of the study is:
Primary:
• To demonstrate superiority of fianlimab + cemiplimab compared to pembrolizumab, as measured by progression-free survival (PFS).
Secondary:
• To demonstrate superiority of fianlimab (REGN3767) + cemiplimab compared to pembrolizumab, as measured by overall survival (OS).
• To demonstrate superiority in ORR with fianlimab + cemiplimab compared to pembrolizumab.
• To characterize the objective response rate (ORR), PFS, and OS with fianlimab + cemiplimab compared to cemiplimab to inform the contribution of each components.
• To assess immunogenicity of fianlimab and cemiplimab.
• To assess impact of fianlimab + cemiplimab on physical functioning and role functioning and global health status/quality of life, as compared to pembrolizumab in adults.
• To characterize safety and tolerability of treatment in patients 12 to <18 years of age.
• To characterize ORR, PFS, and OS with treatment in patients 12 to <18 years of age.
• To assess the safety and tolerability of fianlimab + cemiplimab compared to pembrolizumab and to cemiplimab.
• To characterize pharmacokinetics (PK) of treatment using sparse PK sampling in patients aged ≥12 year

PI: Professor Ntobeko Ntusi & Professor Paul Leeson

Women who experience high blood pressure during pregnancy are at increased risk of developing cardiac and vascular diseases later in life. They show changes in their heart, brain, and blood vessels long before they develop high blood pressure. We therefore think that these changes develop slowly over the course of the life of the woman and establish their risk of later disease.
Through better understanding of the MRI pattern of changes across multiple parts of the body following a hypertensive pregnancy, we aim to identify how advanced the underlying disease is for an individual and how the disease is likely to develop over the next few years.
Data including MRI images of the heart, brain and blood vessels will be acquired in women 6-12 months after their pregnancy. The initial analysis will focus on assessing differences between women who have had a normotensive pregnancy and those who have had a hypertensive pregnancy or pre-eclampsia at a single timepoint.
This dataset will then be used in conjunction with previously acquired data in women who have experienced a hypertensive pregnancy in the UK to find out whether patterns of change differ between South-Africa and the UK. We will combine information from different measures at the same time and use the machine learning models to learn the patterns of change that occur as someone progresses from a healthy to a diseased state. This will allow us to identify patterns of hypertensive disease development and may open doors to improved interventions and therapies tailored to individuals.
The study population will consist of a total of 250 women with 75 experiencing a pre-eclampsia pregnancy, 75 women experiencing a hypertensive pregnancy and 100 women experiencing a normal pregnancy.
Participants will be mother-child, or caregiver-child, pairs recruited from our previous HBS. In HBS we recruited 226 Xhosa-speaking pregnant women, 18 years or older who were attending the Michael Mapongwana Community Health Centre (MMCHC) in Khayelitsha. This community has a high incidence of HIV, with resulting high numbers of infants born with in utero exposure to HIV and ART. Child assessment will begin commence once the child is 6 years old. Inclusion criteria for infants on the study is having been assessed on HBS and willingness to participate in the study. Exclusion criteria include having seroconverted to HIV-positive or having had a serious illness that may affect neurodevelopmental progress and inability to complete study assignment.

PI: Professor Ernesta Meintjes

This study is a follow-on from our previous prospectively recruited cohort study of the effects of HIV and ART exposure on neurodevelopment in uninfected infants (Healthy Baby Study, HBS). The study will recruit mother-child pairs who participated in HBS to examine the effects of pre-and perinatal HIV/ART exposure on neurodevelopment around ages 6 and 8 years, using multimodal neuroimaging and clinical and cognitive assessments. Together with the data collected on HBS, this will enable a longitudinal assessment of effects of HIV/ART exposure on neurodevelopmental outcomes and potential moderation by environmental factors, infant nutrition and maternal well-being and health. We will use MRI to assess brain structure, metabolism and connectivity, and conduct clinical and cognitive assessments around 6 and 8 yrs.

Participants will be mother-child, or caregiver-child, pairs recruited from our previous HBS. In HBS we recruited 226 Xhosa-speaking pregnant women, 18 years or older who were attending the Michael Mapongwana Community Health Centre (MMCHC) in Khayelitsha. This community has a high incidence of HIV, with resulting high numbers of infants born with in utero exposure to HIV and ART. Child assessment will begin commence once the child is 6 years old. Inclusion criteria for infants on the study is having been assessed on HBS and willingness to participate in the study. Exclusion criteria include having seroconverted to HIV-positive or having had a serious illness that may affect neurodevelopmental progress and inability to complete study assignment.

PI: Professor Heather Zar

The Cape Town Adolescent Antiretroviral Cohort (CTAAC) is a prospective longitudinal study funded by the National Institutes of Health. It follows a large cohort of aging perinatally HIV-infected adolescents who are established on antiretroviral therapy to investigate respiratory, cardiovascular, neurocognitive, behavioural and psychosocial development and progression during late childhood and adolescence.

A new focus of the CTAAC study (CTAAC-Heart) is to explore cardiometabolic differences and outcomes between perinatally HIV-infected adolescents, HIV-uninfected controls and a new comparison group - horizontally HIV-infected adolescents.

PI: Dr Jia Fan & Professor Tinashe Mutsvangwa

Fetal alcohol spectrum disorders (FASD) are a range of neurocognitive and behavioral impairments resulting from prenatal alcohol exposure (PAE). Fetal alcohol syndrome (FAS), the most severe form of the FASD, is characterized by small head circumference, growth retardation, and distinctive facial features, including short palpebral fissures, an indistinct (i.e., flat or smooth) philtrum, and a thin vermillion. These facial features have been associated with brain damage and occur between the 10th and 20th weeks of pregnancy. The FAS facial features have been explored by image-based studies. While FASD-related face-brain dysmorphia has been well characterized, little has been reported on the correlation between the syndromic face and brain. Recent improvements in statistical shape models (SSMs), and robust tools for extracting and explaining shape between biological structures, have facilitated accurate brain segmentation and may enable facial shape analyses using Magnetic Resonance (MR) images. Several studies have, however, demonstrated gravity-related changes in facial soft tissue depending on whether a person is in a vertical or horizontal position. Using MR images (where a person is lying) and 3D photographic images (where a person is seated or standing) acquired from healthy subjects. This study will apply a novel integration of MRI and SSM-based analysis to estimate the neural correlates of facial features and brain dysmorphology in children with FASD. One strength of this study is that detailed prospectively obtained information is available about maternal drinking during pregnancy. This study thus provides a unique opportunity to study face-brain dysmorphology in relation to the degree of alcohol exposure in a well-characterized cohort of children. The present study aims to examine (1) the feasibility of SSM-based analysis on facial features estimated using MRI T1 images, and (2) neural correlates of face-brain dysmorphology mediated by maternal drinking during pregnancy.

PI: Dr Jia Fan 

A stroke occurs when the blood supply to an area of the brain is interrupted by either occlusion or haemorrhage. People who suffer a stroke often have long hospitalization and lasting physical and cognitive impairments of varying severity. Stroke rehabilitation programs are highly effective and important to regain independence and quality of life. Rehabilitation programs typically include different therapies, or a combination of therapies, depending on the impairment, including physiotherapy, occupational therapy, and/or speech therapy. Acupuncture is a relatively new approach to stroke rehabilitation, though it has been widely used in East Asia and suggested as an adjunctive therapy by the World Health Organization (WHO). Previous studies have shown improvements in balance, decreased spasticity, and increased muscle strength in stroke patients, as well greater mean blood flow velocity in the brain. The mechanisms of acupuncture and its effects on brain function are, however, poorly understood. This study aims to examine (1) the potential benefits of adjunctive acupuncture therapy during a standard 5-week unilateral stroke rehabilitation stroke rehabilitation programme, and (2) the neural correlates of adjunctive acupuncture treatment. Sixty Participants aged 40-65 will be randomized to one of three treatment arms: (a) standard physiotherapy (PT), (b) PT with true acupuncture (TA), and (c) PT with verum puncture (VA). The objectives are to determine in adults with unilateral limb dysfunction following an ischaemic stroke. First, we will assess whether TA alters physical outcomes, including lower extremity muscle strength, muscle tone, and/or balance, compared to patients receiving PT only or PT and VA. Using MRI, we will assess whether TA alters brain function during movement of the affected limb, as well as functional and structural connectivity, compared to patients receiving PT only or PT and VA. Finally, we will examine whether improvements in physical outcomes are associated with alterations on MRI.

PI: A/Professor Leigh Schrieff-Brown 

The proposed research study expands on a previous study that was conducted by Nina Steenkamp (2021), and has two different aims, with two resultant hypotheses. The first aim is to investigate the prevalence of TBI among South African young offenders and non-offenders. The second aim is to investigate TBI and its association with executive functioning, emotional, behavioral and neuroimaging outcomes in a sample of South African young offenders.
For aim 1: Prevalence of TBI amongst young offenders and non- offenders, we hypothesize that: There will be a higher prevalence of TBI in a sample of young offenders than in a sample of non-offenders in South Africa.

For aim 2: Comparing the behavioral, emotional outcomes, executive functioning, and neuroimaging profiles of young offenders with TBI and young offenders without TBI and comparing that to the non-offender group, we hypothesis that: Young offenders who have sustained one or multiple self-reported TBIs will score more poorly on measures of executive function (both pen and paper and VR measures), emotion, antisocial, and internalizing and externalizing behaviours, with associated structural than young offenders who have not sustained any TBIs, or matched non-offender controls.



PI: Professor Ntobeko Ntusi 

The study has two arms: (1) a cross-sectional study to assess the phenotypes (CMR and histology) and (2) a prospective cohort to assess outcomes and to explore the correlation of imaging biomarkers with clinical events.
Participants included in this study are patients diagnosed of RHD and recommended for CMR imaging by the cardiologists in Groote Schuur Hospital. Up to 50 RHD patients will be included and compared with age, sex and ethnicity matched controls.
Application of the revised Jones criteria of 2015 (Table 1), will be used as the entrance criteria for suspected RHD cases. Up to 1 hundred (100) patients with RHD patients and fifty (50) controls without RHD will be recruited for this study. Scanned participants will be recalled for a follow-up scan to investigate the myocardial changes in the baseline phenotypes.
Eligible participants will be scanned with a 3-Tesla (3T) MRI Siemens Magnetom Skyra scanner with an 18-channel phased array body coil (Siemens, Erlanger, Germany). The scanning exercise will be conducted at the Cape University Body Imaging Centre (CUBIC), Groote Schuur hospital. In myocardial imaging, left and right ventricular mass and volumes, the presence of edema/inflammation (T2 imaging/T2 mapping), myocardial deformation (circumferential and longitudinal strains, strain rates, and strain-time curves with cine DENSE), fibrosis (focal: LGE, global extracellular volume assessment with pre- and post-contrast T1 mapping) and hemodynamic parameter quantification (phase contrast inversion recovery) will be investigated.

PI: Professor Ntobeko Ntusi & Professor Mpiko Ntsekhe

This is a cross-sectional study of ART-treated HIV+ persons (n=100) and HIV uninfected controls (n=100) in South Africa (SA) over age 30 years old, and with an absence of known coronary heart disease (CHD). One-half of participants will be over age 50 years old, resulting in four study groups: a) HIV+ and age ≥50 years, b) HIV+ and age <50 years, c) HIV negative and age ≥50 years, and d) HIV negative and age <50 years. Participants will have comprehensive assessments of myocardial structure and function (and coronary disease) via cardiac magnetic resonance (CMR) imaging, as well as measures of vascular stiffness and blood specimens collected to estimate inflammation and immune activation.
Cardiac Magnetic Resonance (CMR) Outcomes
a. Diffuse myocardial fibrosis: T1 mapping (primary outcome)
b. Myocardial fibrosis: extracellular volume (ECV), late-gadolinium enhancement (LGE)
c. Myocardial inflammation: T1 and T2 mapping
d. Diastolic function: circumferential strain, longitudinal strain, and radial strain
e. Systolic function: Global LV function (via 3D volumetric analysis), circumferential strain, longitudinal strain, and radial strain
f. Coronary ischemia: Infarct/scar by LGE, Myocardial stress perfusion for inducible ischemia, Blood oxygen level dependent (BOLD) imaging.

PI: Professor Dan Stein 

People with psychotic disorders are at a slightly higher risk of committing violence than the general population. Media portrayals often exaggerate this risk, leading to stigma. However, the risk creates significant challenges for people living with psychosis, their family members, and the healthcare system. This study aims to identify biological, psychological and social risk factors of violence in people with psychotic disorders. Participants will be recruited from Valkenberg Hospital and surrounding clinics, falling into three groups: (1) People with psychotic disorders with a history of violence, (2) People with psychotic disorders without a history of violence, (3) Healthy controls. For the MRI component of the study, our objectives are to: (1) Characterise brain functional (rs-fMRI) and structural (sMRI, DTI) markers of psychotic violence using state-of-the art MRI analysis tools and statistical modelling (2) Map brain functional and structural correlates of state and trait risk factors for violence in severe mental disorders, including psychosis symptom load and social cognitive abilities.

PI: Professor Sam Nightingale

The treatment or prevention of Alzheimer’s disease (AD) remains one of humanity’s great unsolved challenges. It is becoming even more critical as the global population ages. There have been great advances in our understanding of protein misfolding and aggregation underlying sporadic AD, but less is known about mechanisms of amyloid production and the physiological role this protein may play in health.
The dramatic changes in longevity for people with HIV associated with modern antiretroviral therapy offers a unique opportunity for a natural experiment exploring mechanisms of AD pathology in the context of the chronic infection and neuroinflammation. Life expectancy for people with HIV now approaches that of HIV-uninfected cohorts, and for the first-time people with HIV are living to an age associated with risk of sporadic AD. South Africa has the largest population of people living with HIV (7.8m people: over 3 times that of any other country) and the largest antiretroviral treatment programme in the world. In our recent community dementia survey in the Eastern Cape of South Africa, 4.8% of all those screened over 70 years of age were HIV positive. When extrapolated across the country, this represents tens of thousands of elderly people living with HIV in South Africa.
There is also a moral imperative for more research in low-income African populations. Research is needed to explore the causes and consequences of dementia to address stark global health inequality and improve outcomes for vulnerable people living with dementia in this setting.
In this study we aim to:
1. Determine the prevalence of cerebral amyloidopathy in people with HIV compared to a HIV-negative population
2. Determine whether the exposure to past and current HIV-related neuroinflammation correlates with presence of cerebral amyloidopathy.
3. Determine the prevalence of clinical AD in and elderly HIV+ve and HIV-ve population.

PI: Professor Ntobeko Ntusi, Professor Chris Longenecker & Professor Markella Zanni

Two-year prospective observational cohort study of cardiovascular magnetic resonance (CMR) to assess myocardial fibrosis and steatosis among antiretroviral therapy (ART)-treated women with HIV compared to age-matched control women without HIV in sub-Saharan Africa (SSA).

PI: Professor E Verburgh 

Epcoritamab is a fully human, immunoglobulin G1-bispecific antibody targeting CD3+ T-cells and CD20+ B-cells. CD20 is expressed on the tumour cells of DLBCL and is a valid and excellent target for eradicating CD20-expressing B cell tumours. The mechanism of action of the drug, is to engage T-cells as effector cells, which in turn will enable the killing of CD20- expressing B-cells and tumor cells – this is the double step action of the bispecific antibody Epcoritimab that enables very specific and effective antitumour action, by harnessing the natural mechanisms of immune effector cell action.

In the currently ongoing global clinical trials, note that the Phase 1/2 Studies GCT3013-01 and GCT3013-02 Arm 1, have shown epcoritamab to have a manageable safety profile and good efficacy in terms of clinically meaningful and durable complete responses (CRs). It has been used both as monotherapy in heavily pretreated relapsed/refractory aggressive non-Hodgkin's lymphoma, and as therapy for newly diagnosed DLBCL in combination with R-CHOP.

CHOP-R has been challenged as best care for DLBCL by many rival protocols or approaches over the past 30 years, however it remains the undoubted gold standard of first-line treatment in DLBCL. This study has the potential to unlock a new treatment combination that can offer definite cure to a larger percentage of DLBCL patients.

PI: Dr Samantha Brooks

It is currently unclear whether cognitive training using a working memory task, is effective in reducing obsessive-compulsive symptoms and neuropsychological deficits in patients with OCD. This project will involve an intervention consisting of 8 weeks of cognitive training.  Working memory, neuropsychological functioning and OCD symptomatology will be assessed pre and post-treatment. Furthermore neuroimaging using sMRI and fMRI will be conducted at baseline as well as at the end of the 8 week period.  The scan will serve to show any structural or functional changes in the frontostriatal area involved with working memory. To our knowledge, this is one of the first studies to date to examine whether cognitive training improves symptoms in OCD.