ORCID Profile
0000-0001-9667-3872
Current Organisation
Garvan Institute of Medical Research
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Publisher: Impact Journals, LLC
Date: 21-01-2020
Publisher: Cold Spring Harbor Laboratory
Date: 03-07-2022
DOI: 10.1101/2022.06.30.22277092
Abstract: Immune checkpoint blockade impedes the negative regulatory signals for T-cell response and permits more effective immune detection and eradication of cancer cells. This single-arm phase II clinical trial (ACTRN12616001019493) within the Molecular Screening and Therapeutics (MoST) program evaluates the clinical activity and safety of combination immunotherapy with durvalumab and tremelimumab in patients with advanced cancers, prioritsing rare cancers ( per 100,000 annual incidence) and patients having failed standard treatments for their cancer type. Eligible patients were determined by the molecular tumour board based on the absence of actionable genomic findings (n=64) and biomarker enriched (n=48) at screening. Patients received durvalumab 1500 mg and tremelimumab 75 mg every four weeks for 4 cycles, followed by durvalumab alone for another 9 cycles. The primary endpoint was progression-free survival at 6 months (PFS6) and secondary endpoints included objective response, time to progression (TTP) on trial to TTP on prior therapy (TTP2/TTP1 .3), overall survival and treatment tolerability. Between December 2016 and 2019, 112 patients were enrolled on the study. There was a female predominance (55%), most had an ECOG performance status of 0 (66%), aged years (75%), with rare cancers (84%). The PFS6 rate was 32% (95% CI 23 to 40%) 16 of 112(14%) achieved an objective response TTP2/TTP1 .3 for 22 of 63 (35%) patients with an evaluable ratio median overall survival 11.9 months (95% CI 11.0 to 14.8), and there were no new safety concerns. High tumour cell PD-L1 correlated with improved PFS and OS and TMB with PFS alone. More PD-1 + CD4 + T-cells and circulating follicular T-helper (cTfh) cells at baseline were strongly associated with better PFS and OS. Durvalumab plus tremelimumab demonstrated a signal of clinical activity in treatment-refractory patients with rare cancers. A PFS6 of 32% and 35% of patients achieving a TTP2/TTP1 .3 suggests an improved disease trajectory on trial. Translational correlates provided insights into biological associations with clinical outcomes across tumour types.
Publisher: Springer Science and Business Media LLC
Date: 24-08-2016
DOI: 10.1038/SREP31907
Abstract: Fragility fractures caused by osteoporosis affect millions of people worldwide every year with significant levels of associated morbidity, mortality and costs to the healthcare economy. The pathogenesis of declining bone mineral density is poorly understood but it is inherently related to increasing age. Growing evidence in recent years, especially that provided by mouse models, suggest that accumulating somatic mitochondrial DNA mutations may cause the phenotypic changes associated with the ageing process including osteoporosis. Methods to study mitochondrial abnormalities in in idual osteoblasts, osteoclasts and osteocytes are limited and impair our ability to assess the changes seen with age and in animal models of ageing. To enable the assessment of mitochondrial protein levels, we have developed a quadruple immunofluorescence method to accurately quantify the presence of mitochondrial respiratory chain components within in idual bone cells. We have applied this technique to a well-established mouse model of ageing and osteoporosis and show respiratory chain deficiency.
Publisher: Elsevier BV
Date: 10-2018
Publisher: Cold Spring Harbor Laboratory
Date: 04-2019
DOI: 10.1101/MCS.A003764
Abstract: Adrenocortical carcinoma is a rare malignancy with a poor prognosis and few treatment options. Molecular characterization of this cancer remains limited. We present a case of an adrenocortical carcinoma (ACC) in a 37-yr-old female, with dual lung metastases identified 1 yr following commencement of adjuvant mitotane therapy. As standard therapeutic regimens are often unsuccessful in ACC, we undertook a comprehensive genomic study into this case to identify treatment options and monitor disease progress. We performed targeted and whole-genome sequencing of germline, primary tumor, and both metastatic tumors from this patient and monitored recurrence over 2 years using liquid biopsy for ctDNA and steroid hormone measurements. Sequencing revealed the primary and metastatic tumors were hyperhaploid, with extensive loss of heterozygosity but few structural rearrangements. Loss-of-function mutations were identified in MSH2 , TP53 , RB1 , and PTEN , resulting in tumors with mismatch repair signatures and microsatellite instability. At the cellular level, tumors were populated by mitochondria-rich oncocytes. Longitudinal ctDNA mutation and hormone profiles were unable to detect micrometastatic disease, consistent with clinical indicators of disease remission. The molecular signatures in our ACC case suggested immunotherapy in the event of disease progression however, the patient remains free of cancer. The extensive molecular analysis presented here could be applied to other rare and/or poorly stratified cancers to identify novel or repurpose existing therapeutic options, thereby broadly improving diagnoses, treatments, and prognoses.
Publisher: Springer Science and Business Media LLC
Date: 23-01-2020
DOI: 10.1038/S41467-020-14286-0
Abstract: Chromosome arm aneuploidies (CAAs) are pervasive in cancers. However, how they affect cancer development, prognosis and treatment remains largely unknown. Here, we analyse CAA profiles of 23,427 tumours, identifying aspects of tumour evolution including probable orders in which CAAs occur and CAAs predicting tissue-specific metastasis. Both haematological and solid cancers initially gain chromosome arms, while only solid cancers subsequently preferentially lose multiple arms. 72 CAAs and 88 synergistically co-occurring CAA pairs multivariately predict good or poor survival for 58% of 6977 patients, with negligible impact of whole-genome doubling. Additionally, machine learning identifies 31 CAAs that robustly alter response to 56 chemotherapeutic drugs across cell lines representing 17 cancer types. We also uncover 1024 potential synthetic lethal pharmacogenomic interactions. Notably, in predicting drug response, CAAs substantially outperform mutations and focal deletions/ lifications combined. Thus, CAAs predict cancer prognosis, shape tumour evolution, metastasis and drug response, and may advance precision oncology.
Publisher: Wiley
Date: 09-10-2018
DOI: 10.1111/BPA.12640
Publisher: Oxford University Press (OUP)
Date: 30-04-2016
DOI: 10.1093/NAR/GKW382
Publisher: Wiley
Date: 30-05-2016
DOI: 10.1111/NAN.12238
Publisher: Elsevier BV
Date: 10-2014
Publisher: Wiley
Date: 04-2018
Abstract: Mitochondrial dysfunction within the pulmonary vessels has been shown to contribute to the pathology of idiopathic pulmonary arterial hypertension (IPAH). We investigated the hypothesis of whether impaired exercise capacity observed in IPAH patients is in part due to primary mitochondrial oxidative phosphorylation (OXPHOS) dysfunction in skeletal muscle. This could lead to potentially new avenues of treatment beyond targeting the pulmonary vessels. Nine clinically stable participants with IPAH underwent cardiopulmonary exercise testing, in vivo and in vitro assessment of mitochondrial function by 31 P‐magnetic resonance spectroscopy ( 31 P‐MRS) and laboratory muscle biopsy analysis. 31 P‐MRS showed abnormal skeletal muscle bioenergetics with prolonged recovery times of phosphocreatine and abnormal muscle pH handling. Histochemistry and quadruple immunofluorescence performed on muscle biopsies showed normal function and subunit protein abundance of the complexes within the OXPHOS system. Our findings suggest that there is no primary mitochondrial OXPHOS dysfunction but raises the possibility of impaired oxygen delivery to the mitochondria affecting skeletal muscle bioenergetics during exercise.
Publisher: Wiley
Date: 07-02-2018
DOI: 10.1002/ACN3.532
Publisher: Wiley
Date: 30-09-2016
DOI: 10.1111/NAN.12282
Publisher: Wiley
Date: 19-09-2016
DOI: 10.1002/ANA.24736
Abstract: The m.3243A G MTTL1 mutation is the most common cause of mitochondrial disease yet there is limited awareness of intestinal pseudo‐obstruction (IPO) in this disorder. We aimed to determine the prevalence, severity, and clinical outcome of patients with m.3243A G‐related mitochondrial disease manifesting with IPO. In this large, observational cohort study, we assessed the clinical, molecular, and radiological characteristics of patients with genetically determined m.3243A G‐related mitochondrial disease, who presented with severe symptoms suggestive of bowel obstruction in the absence of an occluding lesion. Between January 2009 and June 2015, 226 patients harbouring the m.3243A G mutation were recruited to the Medical Research Council Centre Mitochondrial Disease Patient Cohort, Newcastle. Thirty patients (13%) presented acutely with IPO. Thirteen of these patients had a preceding history of stroke‐like episodes, whereas 1 presented 27 years previously with their first stroke‐like episode. Eight patients developed IPO concomitantly during an acute stroke‐like episode. Regression analysis suggested stroke was the strongest predictor for development of IPO, in addition to cardiomyopathy, low body mass index and high urinary mutation load. Poor clinical outcome was observed in 6 patients who underwent surgical procedures. Our findings suggest, in this common mitochondrial disease, that IPO is an under‐recognized, often misdiagnosed clinical entity. Poor clinical outcome associated with stroke and acute surgical intervention highlights the importance of the neurologist having a high index of suspicion, particularly in the acute setting, to instigate timely coordination of appropriate care and management with other specialists. Ann Neurol 2016 :686–692
Publisher: Oxford University Press (OUP)
Date: 17-07-2015
Publisher: Springer Science and Business Media LLC
Date: 25-07-2018
Publisher: Springer Science and Business Media LLC
Date: 14-09-2023
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 19-06-2012
DOI: 10.1167/12.6.24
Publisher: Impact Journals, LLC
Date: 08-10-2019
Publisher: Cold Spring Harbor Laboratory
Date: 22-12-2020
DOI: 10.1101/2020.12.18.20248521
Abstract: While several key resources exist that interpret therapeutic significance of genomic alterations in cancer, many regional real-world issues limit access to drugs. There is a need for a pragmatic, evidence-based, context-adapted tool to guide clinical management based on molecular biomarkers. A compendium of approved and experimental therapies with associated biomarkers was built following a survey of drug regulatory databases, existing knowledge bases, and published literature. Each biomarker-disease-therapy triplet was then categorized using a tiering system reflective of key therapeutic considerations: approved and reimbursed standard-of-care therapies with respect to a jurisdiction (Tier 1), evidence of efficacy or approval in another jurisdiction (Tier 2), evidence of antitumour activity (Tier 3), and plausible biological rationale (Tier 4). Two resistance categories were defined: lack of efficacy (Tier R1), and lack of antitumor activity (Tier R2). Following comprehensive literature review and appraisal, we developed a curated knowledge base focused on drugs relevant and accessible in the Australian healthcare system (TOPOGRAPH: Therapy Oriented Precision Oncology Guidelines for Recommending Anticancer Pharmaceuticals). As of November 2020, TOPOGRAPH comprised 2810 biomarker-disease-therapy triplets in 989 expert-appraised entries, including 373 therapies, 199 predictive biomarkers, and 106 cancer types. In the 345 biomarker-linked therapies catalogued, 84 (24%) and 65 (19%) therapies in contexts of different cancer types have Tier 1 and 2 designations respectively, while 271 (79%) therapies were supported by preclinical studies, early clinical trials, retrospective studies, or case series (Tiers 3 and 4). A total of 119 of 373 (33%) therapies associated with biomarkers of resistance were also catalogued. A clinical algorithm was also developed to support therapeutic decision-making using predictive biomarkers. This resource is accessible online at topograph.info/ . TOPOGRAPH is intended to support oncologists with context-appropriate clinical decision-making– optimising selection and accessibility of the most appropriate targeted therapy for any given genomic biomarker. Our approach can be readily adapted to build jurisdiction-specific resources to standardise decision-making in precision oncology.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Springer Science and Business Media LLC
Date: 19-05-2015
DOI: 10.1038/SREP09906
Abstract: Mitochondrial DNA (mtDNA) mutations are commonly found in the skeletal muscle of patients with mitochondrial disease, inflammatory myopathies and sarcopenia. The majority of these mutations are mtDNA deletions, which accumulate to high levels in in idual muscle fibres causing a respiratory defect. Most mtDNA deletions are major arc deletions with breakpoints located between the origin of light strand (O L ) and heavy strand (O H ) replication within the major arc. However, under certain disease conditions, rarer, minor arc deletions are detected. Currently, there are few techniques which would allow the detection and quantification of both types of mtDNA deletions in single muscle fibres. We have designed a novel triplex real-time PCR assay which simultaneously lifies the MT-ND4 gene in the major arc, the MT-ND1 gene in the minor arc and the non-coding D-Loop region. We demonstrate that this assay is a highly sensitive and reliable tool for the detection and quantification of a broad range of major and minor arc mtDNA deletions with the potential to investigate the molecular pathogenesis in both research and diagnostic settings.
Publisher: Springer Science and Business Media LLC
Date: 26-06-2023
DOI: 10.1038/S41416-023-02311-0
Abstract: To determine the safety and efficacy of PARP plus PD-L1 inhibition (olaparib + durvalumab, O + D) in patients with advanced solid, predominantly rare cancers harbouring homologous recombination repair (HRR) defects. In total, 48 patients were treated with O + D, 16 with BRCA1/2 alterations (group 1) and 32 with other select HRR alterations (group 2). Overall, 32 (66%) patients had rare or less common cancers. The primary objective of this single-arm Phase II trial was a progression-free survival rate at 6 months (PFS6). Post hoc exploratory analyses were conducted on archival tumour tissue and serial bloods. The PFS6 rate was 35% and 38% with durable objective tumour responses (OTR) in 3(19%) and 3(9%) in groups 1 and 2, respectively. Rare cancers achieving an OTR included cholangiocarcinoma, perivascular epithelioid cell (PEComa), neuroendocrine, gallbladder and endometrial cancer. O + D was safe, with five serious adverse events related to the study drug(s) in 3 (6%) patients. A higher proportion of CD38 high B cells in the blood and higher CD40 expression in tumour was prognostic of survival. O + D demonstrated no new toxicity concerns and yielded a clinically meaningful PFS6 rate and durable OTRs across several cancers with HRR defects, including rare cancers.
Publisher: Springer Science and Business Media LLC
Date: 16-08-2017
Publisher: Springer Science and Business Media LLC
Date: 15-10-2015
DOI: 10.1038/SREP15037
Abstract: Oxidative phosphorylation defects in human tissues are often challenging to quantify due to a mosaic pattern of deficiency. Biochemical assays are difficult to interpret due to the varying enzyme deficiency levels found in in idual cells. Histochemical analysis allows semi-quantitative assessment of complex II and complex IV activities, but there is no validated histochemical assay to assess complex I activity which is frequently affected in mitochondrial pathology. To help improve the diagnosis of mitochondrial disease and to study the mechanisms underlying mitochondrial abnormalities in disease, we have developed a quadruple immunofluorescent technique enabling the quantification of key respiratory chain subunits of complexes I and IV, together with an indicator of mitochondrial mass and a cell membrane marker. This assay gives precise and objective quantification of protein abundance in large numbers of in idual muscle fibres. By assessing muscle biopsies from subjects with a range of different mitochondrial genetic defects we have demonstrated that specific genotypes exhibit distinct biochemical signatures in muscle, providing evidence for the diagnostic use of the technique, as well as insight into the underlying molecular pathology. Stringent testing for reproducibility and sensitivity confirms the potential value of the technique for mechanistic studies of disease and in the evaluation of therapeutic approaches.
Publisher: Wiley
Date: 04-03-2014
DOI: 10.1111/NAN.12149
Publisher: Wiley
Date: 03-05-2017
DOI: 10.1111/BJH.14649
Abstract: Multiple Myeloma (MM) is a haematological malignancy characterised by the clonal expansion of plasma cells (PCs) within the bone marrow. Despite advances in therapy, MM remains a largely incurable disease with a median survival of 6 years. In almost all cases, the development of MM is preceded by the benign PC condition Monoclonal Gammopathy of Undetermined Significance (MGUS). Recent studies show that the transformation of MGUS to MM is associated with complex genetic changes. Understanding how these changes contribute to evolution will present targets for clinical intervention. We discuss three models of MM evolution the linear, the expansionist and the intraclonal heterogeneity models. Of particular interest is the intraclonal heterogeneity model. Here, distinct populations of MM PCs carry differing combinations of genetic mutations. Acquisition of additional mutations can contribute to subclonal lineages where "driver" mutations may influence selective pressure and dominance, and "passenger" mutations are neutral in their effects. Furthermore, studies show that clinical intervention introduces additional selective pressure on tumour cells and can influence subclone survival, leading to therapy resistance. This review discusses how Next Generation Sequencing approaches are revealing critical insights into the genetics of MM development, disease progression and treatment. MM disease progression will illuminate possible mechanisms underlying the tumour.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 11-2022
DOI: 10.1200/PO.22.00263
Publisher: Elsevier BV
Date: 10-2016
Publisher: Elsevier BV
Date: 11-2016
Publisher: Public Library of Science (PLoS)
Date: 04-12-2014
Publisher: Society for Neuroscience
Date: 24-08-2011
DOI: 10.1523/JNEUROSCI.3112-11.2011
Abstract: Developing retinal ganglion cells fire in correlated spontaneous bursts, resulting in propagating waves with robust spatiotemporal features preserved across development and species. Here we investigate the effects of homeostatic adaptation on the circuits controlling retinal waves. Mouse retinal waves were recorded in vitro for up to 35 h with a multielectrode array in presence of the GABA A antagonist bicuculline, allowing us to obtain a precise, time-resolved characterization of homeostatic effects in this preparation. Experiments were performed at P4–P6, when GABA A signaling is depolarizing in ganglion cells, and at P7–P10, when GABA A signaling is hyperpolarizing. At all ages, bicuculline initially increased the wave sizes and other activity metrics. At P5–P6, wave sizes decreased toward control levels within a few hours while firing remained strong, but this ability to compensate disappeared entirely from P7 onwards. This demonstrates that homeostatic control of spontaneous retinal activity maintains specific network dynamic properties in an age-dependent manner, and suggests that the underlying mechanism is linked to GABA A signaling.
Publisher: EMBO
Date: 07-05-2018
Publisher: Springer Science and Business Media LLC
Date: 23-06-2021
DOI: 10.1038/S41698-021-00194-Z
Abstract: While several resources exist that interpret therapeutic significance of genomic alterations in cancer, many regional real-world issues limit access to drugs. There is a need for a pragmatic, evidence-based, context-adapted tool to guide clinical management based on molecular biomarkers. To this end, we have structured a compendium of approved and experimental therapies with associated biomarkers following a survey of drug regulatory databases, existing knowledge bases, and published literature. Each biomarker-disease-therapy triplet was categorised using a tiering system reflective of key therapeutic considerations: approved and reimbursed therapies with respect to a jurisdiction (Tier 1), evidence of efficacy or approval in another jurisdiction (Tier 2), evidence of antitumour activity (Tier 3), and plausible biological rationale (Tier 4). Two resistance categories were defined: lack of efficacy (Tier R1) or antitumor activity (Tier R2). Based on this framework, we curated a digital resource focused on drugs relevant in the Australian healthcare system (TOPOGRAPH: Therapy Oriented Precision Oncology Guidelines for Recommending Anticancer Pharmaceuticals). As of November 2020, TOPOGRAPH comprised 2810 biomarker-disease-therapy triplets in 989 expert-appraised entries, including 373 therapies, 199 biomarkers, and 106 cancer types. In the 345 therapies catalogued, 84 (24%) and 65 (19%) were designated Tiers 1 and 2, respectively, while 271 (79%) therapies were supported by preclinical studies, early clinical trials, retrospective studies, or case series (Tiers 3 and 4). A companion algorithm was also developed to support rational, context-appropriate treatment selection informed by molecular biomarkers. This framework can be readily adapted to build similar resources in other jurisdictions to support therapeutic decision-making.
Publisher: Wiley
Date: 05-11-2018
DOI: 10.1002/PATH.5156
Publisher: Research Square Platform LLC
Date: 04-03-2021
DOI: 10.21203/RS.3.RS-254137/V1
Abstract: BACKGROUND: The D-type cyclin and cyclin dependent kinase 4/6 (CDK) complex phosphorylates retinoblastoma protein, thereby driving cell cycle progression. This process is blocked by inhibitors of CDK4/6. As part of the Molecular Screening and Therapeutics program, this phase IIa trial tested the clinical activity of CDK4/6 inhibitor monotherapy in tumors with cell cycle pathway alterations. PATIENTS AND METHODS: Eligible patients ≥ 18 years old, with advanced or metastatic solid cancers, along with lification of CDK4/6, CCND1/2/3, or loss of function alterations in CDKN2A were recruited. The primary objective of this signal-seeking trial was to evaluate the clinical activity of palbociclib – a composite of objective responses and the ratio of time to progression (TTP) on palbociclib, to TTP on treatment preceding trial entry. RESULTS: Ten patients had CDK4/CDK6 or Cyclin D1 lifications, six patients had CDKN2A deletions. After a median follow-up of 35 months, there were no objective responses. Seven patients had stable disease and one had non-complete response/non-progressive disease (non-CR/non-PD) based on evaluation of a non-target lesion. Two of these seven patients maintained stable disease for at least 6 months, as did the patient with non-CR/non-PD. Median PFS and OS were 3.5 and 11.0 months respectively. No unexpected toxicities were observed. Translational correlates yielded strategies for targeting cell cycle interactions with other molecular pathways and the immune system. CONCLUSION: Palbociclib monotherapy was not associated with any objective responses, but stable disease lasting at least 6 months was observed in 19% of patients. There was no clear relationship with alteration type or histotype. The signals of immune activation provide insights into the design of future trials, with a combination approach adding checkpoint blockade to CDK4/6 inhibition.
Publisher: Springer Science and Business Media LLC
Date: 19-11-2019
DOI: 10.1038/S41598-019-52000-3
Abstract: Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA s les were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein ( AIP ) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of % and precision of %. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy.
Publisher: Public Library of Science (PLoS)
Date: 15-11-2012
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.JNEUMETH.2018.03.012
Abstract: Neuronal networks typically comprise heterogeneous populations of neurons. A core objective when seeking to understand such networks, therefore, is to identify what roles these different neuronal classes play. Acquiring single cell electrophysiology data for multiple cell classes can prove to be a large and daunting task. Alternatively, Ca We therefore developed a strategy for combining cellular electrophysiology, Ca We illustrate the methodology for analyses of activity profiles during epileptiform events recorded in mouse brain slices. We further demonstrate the activity profile of a population of parvalbumin-positive interneurons prior, during, and following a seizure-like event. Current approaches to Ca We present a new approach for analysing Ca
Publisher: MDPI AG
Date: 08-01-2018
Publisher: Springer Science and Business Media LLC
Date: 26-03-2018
DOI: 10.1038/S41531-018-0044-6
Abstract: Mitochondrial dysfunction within the cell bodies of substantia nigra neurons is prominent in both ageing and Parkinson’s disease. The loss of dopaminergic substantia nigra neurons in Parkinson’s disease is associated with loss of synapses within the striatum, and this may precede neuronal loss. We investigated whether mitochondrial changes previously reported within substantia nigra neurons were also seen within the synapses and axons of these neurons. Using high resolution quantitative fluorescence immunohistochemistry we determined mitochondrial density within remaining dopaminergic axons and synapses, and quantified deficiencies of mitochondrial Complex I and Complex IV in these compartments. In Parkinson’s disease mitochondrial populations were increased within axons and the mitochondria expressed higher levels of key electron transport chain proteins compared to controls. Furthermore we observed synapses which were devoid of mitochondrial proteins in all groups, with a significant reduction in the number of these ‘empty’ synapses in Parkinson’s disease. This suggests that neurons may attempt to maintain mitochondrial populations within remaining axons and synapses in Parkinson’s disease to facilitate continued neural transmission in the presence of neurodegeneration, potentially increasing oxidative damage. This compensatory event may represent a novel target for future restorative therapies in Parkinson’s disease.
Publisher: Oxford University Press (OUP)
Date: 25-11-2013
DOI: 10.1093/BRAIN/AWT321
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for John Grady.