Julie Vallortigara - Academia.edu (original) (raw)
Papers by Julie Vallortigara
PLOS ONE, Dec 5, 2013
Diabetic neuropathy is a severe complication of long-standing diabetes and one of the major etiol... more Diabetic neuropathy is a severe complication of long-standing diabetes and one of the major etiologies of neuropathic pain. Diabetes is associated with an increased formation of reactive oxygen species and the electrophilic dicarbonyl compound methylglyoxal (MG). Here we show that MG stimulates heterologously expressed TRPA1 in CHO cells and natively expressed TRPA1 in MDCK cells and DRG neurons. MG evokes [Ca 2+ ] i-responses in TRPA1 expressing DRG neurons but is without effect in neurons cultured from Trpa1 2/2 mice. Consistent with a direct, intracellular action, we show that methylglyoxal is significantly more potent as a TRPA1 agonist when applied to the intracellular face of excised membrane patches than to intact cells. Local intraplantar administration of MG evokes a pain response in Trpa1 +/+ but not in Trpa1 2/2 mice. Furthermore, persistently increased MG levels achieved by two weeks pharmacological inhibition of glyoxalase-1 (GLO-1), the rate-limiting enzyme responsible for detoxification of MG, evokes a progressive and marked thermal (cold and heat) and mechanical hypersensitivity in wildtype but not in Trpa1 2/2 mice. Our results thus demonstrate that TRPA1 is required both for the acute pain response evoked by topical MG and for the long-lasting pronociceptive effects associated with elevated MG in vivo. In contrast to our observations in DRG neurons, MG evokes indistinguishable [Ca 2+ ] i-responses in pancreatic bcells cultured from Trpa1 +/+ and Trpa1 2/2 mice. In vivo, the TRPA1 antagonist HC030031 impairs glucose clearance in the glucose tolerance test both in Trpa1 +/+ and Trpa1 2/2 mice, indicating a non-TRPA1 mediated effect and suggesting that results obtained with this compound should be interpreted with caution. Our results show that TRPA1 is the principal target for MG in sensory neurons but not in pancreatic b-cells and that activation of TRPA1 by MG produces a painful neuropathy with the behavioral hallmarks of diabetic neuropathy.
Research Square (Research Square), May 3, 2023
Background Little is known about the costs of treating ataxia and whether treatment at a speciali... more Background Little is known about the costs of treating ataxia and whether treatment at a specialist ataxia centre affects the cost of care. The aim of this study was to investigate whether patients who attended specialist ataxia centres in three European countries reported differences in their health care use and costs compared with patients who did not attend a specialist ataxia centre. We compared mean resource use and health service costs per patient affected by ataxia in the United Kingdom, Italy and Germany over a 12-month period. Data were obtained from a survey distributed to people with ataxia in the three countries. We compared mean resource use for each contact type and costs, stratifying patients by whether they were currently attending a specialist ataxia centre or had never attended one. Results Responses were received from 181 patients from the United Kingdom, 96 from Italy and 43 from Germany. Differences in the numbers of contacts for most types of health service use between the specialist ataxia centre and non-specialist ataxia centre groups were non-signi cant. In the United Kingdom the mean total cost per patient was €2209 for non-specialist ataxia centre patients and €1813 for specialist ataxia centre patients (P = 0.59). In Italy these gures were €2126 and €1971, respectively (P = 0.84). In Germany they were €2431 and €4087, respectively (P = 0.19). Inpatient stays made the largest contribution to total costs. Conclusions Within each country, resource use and costs were broadly similar for specialist ataxia centre and non-specialist ataxia centre groups. There were differences between countries in terms of health care contacts and costs.
Orphanet Journal of Rare Diseases, Jan 4, 2022
Background: The development of new therapies may rely on the conduct of human experimentation as ... more Background: The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. Methods: We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich's Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status. Results: Of 342 respondents, 204 reported a diagnosis of Friedreich's ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration. Conclusions: Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials.
Value in Health, Nov 1, 2016
Alzheimers & Dementia, Jul 1, 2011
Background: Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) account for 10... more Background: Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) account for 10-20% of dementias. The classical neuropathological and neurochemical characteristics include the widespread presence of a-synuclein aggregates in forms of cortical Lewy bodies (LBs). The number of LBs in cortical regions correlates with cognitive impairment in DLB and PDD. Since the ubiquitine-proteasome system (UPS) is the major non-lysosomal pathway for a-synuclein degradation, dysfunction of this system could play a role in the development of a-synuclein aggregates. Methods: The current study examine, mRNA expression (qRT-PCR) and protein levels (western blotting) of a3, ß2, ß6 and Rpt6 subunits of the proteasome and the three associated catalytic activities in post-mortem frontal cortex area (BA 9) from DLB and PDD patients in comparison to age-matched controls. Clinical and pathological data were available for the cases studied (duration of dementia and Parkinsonism, MMSE score, CERAD plaque, Braak stage and a-synuclein scores). Results: Protein expression of the a3 and Rpt6 ATPase sub-unit proteins were significantly lower in only PDD group compared with controls (-40% and -50% respectively), although no differences in the mRNA expression of any of the subunits have been shown between DLB, PDD and control cases. Interestingly all proteasome activities were significantly reduced in PDD patients BA 9 extracts compared to both controls and DLD patients (-58% for chymotrypsin-like, -48% for trypsin-like and -71% for PGPH activities, compared to controls level). In the combined DLB/PDD group, all these three activities and the protein level of Rpt6 subunit correlated inversely with the duration of Parkinsonism. Furthermore the level of Rpt6 expression negatively correlated with the a-synuclein burden in the frontal cortex of these PDD cases (Rs -0.64, p 1⁄4 0.004), and the CERAD plaque score was positively associated with chymotrypsin-like activity (Rs 0.797, < 0.001). Conclusions: These findings indicate that dysfunction of the UPS in the cerebral cortex is a feature of PDD (but not DLB) that occurs at a later stage of the disease process, possibly as a consequence of a-synuclein accumulation. Proteasome activation may therefore have limited utility for the early treatment of Lewy body dementias, however this approach may have benefits in slowing disease progression.
<p>Dataset1: The dataset includes the values of Dynamin1 and phospho-/total CaMKII measured... more <p>Dataset1: The dataset includes the values of Dynamin1 and phospho-/total CaMKII measured in the prefrontal cortex, used for the statistic analysis. The first three columns report the semi-quantitative scoring of AD and Lewy Body pathology in this brain region.</p> <p>Dataset2: The dataset includes the values of Dynamin1 and phospho-/total CaMKII measured in the anterior cingulated gyrus, used for the statistic analysis. The first three columns report the semi-quantitative scoring of AD and Lewy Body pathology in this brain region.</p> <p>Dataset3: The dataset includes the values of Dynamin1 and phospho-/total CaMKII measured in the parietal cortex, used for the statistic analysis. The first three columns report the semi-quantitative scoring of AD and Lewy Body pathology in this brain region.</p
Alzheimers & Dementia, Jul 1, 2017
Additional file 4: Barriers to trial participation.
Additional file 2: Symptoms patients want addressed.
Additional file 5: Level of evidence.
Additional file 3: Reasons for trial participation.
Additional file 1: Survey questionnaire.
Orphanet Journal of Rare Diseases, 2019
The progressive ataxias are a group of rare and complicated neurological disorders, knowledge of ... more The progressive ataxias are a group of rare and complicated neurological disorders, knowledge of which is often poor among healthcare professionals (HCPs). The patient support group Ataxia UK, recognising the lack of awareness of this group of conditions, has developed medical guidelines for the diagnosis and management of ataxia. Although ataxia can be a symptom of many common conditions, the focus here is on the progressive ataxias, and include hereditary ataxia (e.g. spinocerebellar ataxia (SCA), Friedreich's ataxia (FRDA)), idiopathic sporadic cerebellar ataxia, and specific neurodegenerative disorders in which ataxia is the dominant symptom (e.g. cerebellar variant of multiple systems atrophy (MSA-C)). Over 100 different disorders can lead to ataxia, so diagnosis can be challenging. Although there are no disease-modifying treatments for most of these entities, many aspects of the conditions are treatable, and their identification by HCPs is vital. The early diagnosis and management of the (currently) few reversible causes are also of paramount importance. More than 30 UK health professionals with experience in the field contributed to the guidelines, their input reflecting their respective clinical expertise in various aspects of ataxia diagnosis and management. They reviewed the published literature in their fields, and provided summaries on "best" practice, including the grading of evidence available for interventions, using the Guideline International Network (GIN) criteria, in the relevant sections. A Guideline Development Group, consisting of ataxia specialist neurologists and representatives of Ataxia UK (including patients and carers), reviewed all sections, produced recommendations with levels of evidence, and discussed modifications (where necessary) with contributors until consensus was reached. Where no specific published data existed, recommendations were based on data related to similar conditions (e.g. multiple sclerosis) and/or expert opinion. The guidelines aim to assist HCPs when caring for patients with progressive ataxia, indicate evidence-based (where it exists) and best practice, and act overall as a useful resource for clinicians involved in managing ataxic patients. They do, however, also highlight the urgent need to develop effective disease-modifying treatments, and, given the large number of recommendations based on "good practice points", emphasise the need for further research to provide evidence for effective symptomatic therapies. These guidelines are aimed predominantly at HCPs in secondary care (such as general neurologists, clinical geneticists, physiotherapists, speech and language therapists, occupational therapists, etc.) who provide care for individuals with progressive ataxia and their families, and not ataxia specialists. It is a useful, practical tool to forward to HCPs at the time referrals are made for ongoing care, for example in the community.
Table S1. List of contributors. Table S2. Allied health professional interventions. Table S3. Pal... more Table S1. List of contributors. Table S2. Allied health professional interventions. Table S3. Palliative care. (DOCX 27 kb)
Dementia with Lewy Bodies (DLB) and Parkinson’s Disease Dementia (PDD) together, represent the se... more Dementia with Lewy Bodies (DLB) and Parkinson’s Disease Dementia (PDD) together, represent the second most common cause of dementia, after Alzheimer’s disease (AD). The synaptic dysfunctions underlying the cognitive decline and psychiatric symptoms observed throughout the development of PDD and DLB are still under investigation. In this study we examined the expression level of Dynamin1 and phospho-CaMKII, key proteins of endocytosis and synaptic plasticity respectively, as potential markers of molecular processes specifically deregulated with DLB and/or PDD. In order to measure the levels of these proteins, we isolated grey matter from post-mortem prefrontal cortex area (BA9), anterior cingulated gyrus (BA24) and parietal cortex (BA40) from DLB and PDD patients in comparison to age-matched controls and a group of AD cases. Clinical and pathological data available included the MMSE score, neuropsychiatric history, and semi-quantitative scores for AD pathology (plaques tangles) and f...
Background: The development of new therapies may rely on the conduct of human experimentation as ... more Background: The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. Methods: We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA) sent the survey to their members. Responses were ana...
PLOS ONE, Dec 5, 2013
Diabetic neuropathy is a severe complication of long-standing diabetes and one of the major etiol... more Diabetic neuropathy is a severe complication of long-standing diabetes and one of the major etiologies of neuropathic pain. Diabetes is associated with an increased formation of reactive oxygen species and the electrophilic dicarbonyl compound methylglyoxal (MG). Here we show that MG stimulates heterologously expressed TRPA1 in CHO cells and natively expressed TRPA1 in MDCK cells and DRG neurons. MG evokes [Ca 2+ ] i-responses in TRPA1 expressing DRG neurons but is without effect in neurons cultured from Trpa1 2/2 mice. Consistent with a direct, intracellular action, we show that methylglyoxal is significantly more potent as a TRPA1 agonist when applied to the intracellular face of excised membrane patches than to intact cells. Local intraplantar administration of MG evokes a pain response in Trpa1 +/+ but not in Trpa1 2/2 mice. Furthermore, persistently increased MG levels achieved by two weeks pharmacological inhibition of glyoxalase-1 (GLO-1), the rate-limiting enzyme responsible for detoxification of MG, evokes a progressive and marked thermal (cold and heat) and mechanical hypersensitivity in wildtype but not in Trpa1 2/2 mice. Our results thus demonstrate that TRPA1 is required both for the acute pain response evoked by topical MG and for the long-lasting pronociceptive effects associated with elevated MG in vivo. In contrast to our observations in DRG neurons, MG evokes indistinguishable [Ca 2+ ] i-responses in pancreatic bcells cultured from Trpa1 +/+ and Trpa1 2/2 mice. In vivo, the TRPA1 antagonist HC030031 impairs glucose clearance in the glucose tolerance test both in Trpa1 +/+ and Trpa1 2/2 mice, indicating a non-TRPA1 mediated effect and suggesting that results obtained with this compound should be interpreted with caution. Our results show that TRPA1 is the principal target for MG in sensory neurons but not in pancreatic b-cells and that activation of TRPA1 by MG produces a painful neuropathy with the behavioral hallmarks of diabetic neuropathy.
Research Square (Research Square), May 3, 2023
Background Little is known about the costs of treating ataxia and whether treatment at a speciali... more Background Little is known about the costs of treating ataxia and whether treatment at a specialist ataxia centre affects the cost of care. The aim of this study was to investigate whether patients who attended specialist ataxia centres in three European countries reported differences in their health care use and costs compared with patients who did not attend a specialist ataxia centre. We compared mean resource use and health service costs per patient affected by ataxia in the United Kingdom, Italy and Germany over a 12-month period. Data were obtained from a survey distributed to people with ataxia in the three countries. We compared mean resource use for each contact type and costs, stratifying patients by whether they were currently attending a specialist ataxia centre or had never attended one. Results Responses were received from 181 patients from the United Kingdom, 96 from Italy and 43 from Germany. Differences in the numbers of contacts for most types of health service use between the specialist ataxia centre and non-specialist ataxia centre groups were non-signi cant. In the United Kingdom the mean total cost per patient was €2209 for non-specialist ataxia centre patients and €1813 for specialist ataxia centre patients (P = 0.59). In Italy these gures were €2126 and €1971, respectively (P = 0.84). In Germany they were €2431 and €4087, respectively (P = 0.19). Inpatient stays made the largest contribution to total costs. Conclusions Within each country, resource use and costs were broadly similar for specialist ataxia centre and non-specialist ataxia centre groups. There were differences between countries in terms of health care contacts and costs.
Orphanet Journal of Rare Diseases, Jan 4, 2022
Background: The development of new therapies may rely on the conduct of human experimentation as ... more Background: The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. Methods: We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich's Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status. Results: Of 342 respondents, 204 reported a diagnosis of Friedreich's ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration. Conclusions: Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials.
Value in Health, Nov 1, 2016
Alzheimers & Dementia, Jul 1, 2011
Background: Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) account for 10... more Background: Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) account for 10-20% of dementias. The classical neuropathological and neurochemical characteristics include the widespread presence of a-synuclein aggregates in forms of cortical Lewy bodies (LBs). The number of LBs in cortical regions correlates with cognitive impairment in DLB and PDD. Since the ubiquitine-proteasome system (UPS) is the major non-lysosomal pathway for a-synuclein degradation, dysfunction of this system could play a role in the development of a-synuclein aggregates. Methods: The current study examine, mRNA expression (qRT-PCR) and protein levels (western blotting) of a3, ß2, ß6 and Rpt6 subunits of the proteasome and the three associated catalytic activities in post-mortem frontal cortex area (BA 9) from DLB and PDD patients in comparison to age-matched controls. Clinical and pathological data were available for the cases studied (duration of dementia and Parkinsonism, MMSE score, CERAD plaque, Braak stage and a-synuclein scores). Results: Protein expression of the a3 and Rpt6 ATPase sub-unit proteins were significantly lower in only PDD group compared with controls (-40% and -50% respectively), although no differences in the mRNA expression of any of the subunits have been shown between DLB, PDD and control cases. Interestingly all proteasome activities were significantly reduced in PDD patients BA 9 extracts compared to both controls and DLD patients (-58% for chymotrypsin-like, -48% for trypsin-like and -71% for PGPH activities, compared to controls level). In the combined DLB/PDD group, all these three activities and the protein level of Rpt6 subunit correlated inversely with the duration of Parkinsonism. Furthermore the level of Rpt6 expression negatively correlated with the a-synuclein burden in the frontal cortex of these PDD cases (Rs -0.64, p 1⁄4 0.004), and the CERAD plaque score was positively associated with chymotrypsin-like activity (Rs 0.797, < 0.001). Conclusions: These findings indicate that dysfunction of the UPS in the cerebral cortex is a feature of PDD (but not DLB) that occurs at a later stage of the disease process, possibly as a consequence of a-synuclein accumulation. Proteasome activation may therefore have limited utility for the early treatment of Lewy body dementias, however this approach may have benefits in slowing disease progression.
<p>Dataset1: The dataset includes the values of Dynamin1 and phospho-/total CaMKII measured... more <p>Dataset1: The dataset includes the values of Dynamin1 and phospho-/total CaMKII measured in the prefrontal cortex, used for the statistic analysis. The first three columns report the semi-quantitative scoring of AD and Lewy Body pathology in this brain region.</p> <p>Dataset2: The dataset includes the values of Dynamin1 and phospho-/total CaMKII measured in the anterior cingulated gyrus, used for the statistic analysis. The first three columns report the semi-quantitative scoring of AD and Lewy Body pathology in this brain region.</p> <p>Dataset3: The dataset includes the values of Dynamin1 and phospho-/total CaMKII measured in the parietal cortex, used for the statistic analysis. The first three columns report the semi-quantitative scoring of AD and Lewy Body pathology in this brain region.</p
Alzheimers & Dementia, Jul 1, 2017
Additional file 4: Barriers to trial participation.
Additional file 2: Symptoms patients want addressed.
Additional file 5: Level of evidence.
Additional file 3: Reasons for trial participation.
Additional file 1: Survey questionnaire.
Orphanet Journal of Rare Diseases, 2019
The progressive ataxias are a group of rare and complicated neurological disorders, knowledge of ... more The progressive ataxias are a group of rare and complicated neurological disorders, knowledge of which is often poor among healthcare professionals (HCPs). The patient support group Ataxia UK, recognising the lack of awareness of this group of conditions, has developed medical guidelines for the diagnosis and management of ataxia. Although ataxia can be a symptom of many common conditions, the focus here is on the progressive ataxias, and include hereditary ataxia (e.g. spinocerebellar ataxia (SCA), Friedreich's ataxia (FRDA)), idiopathic sporadic cerebellar ataxia, and specific neurodegenerative disorders in which ataxia is the dominant symptom (e.g. cerebellar variant of multiple systems atrophy (MSA-C)). Over 100 different disorders can lead to ataxia, so diagnosis can be challenging. Although there are no disease-modifying treatments for most of these entities, many aspects of the conditions are treatable, and their identification by HCPs is vital. The early diagnosis and management of the (currently) few reversible causes are also of paramount importance. More than 30 UK health professionals with experience in the field contributed to the guidelines, their input reflecting their respective clinical expertise in various aspects of ataxia diagnosis and management. They reviewed the published literature in their fields, and provided summaries on "best" practice, including the grading of evidence available for interventions, using the Guideline International Network (GIN) criteria, in the relevant sections. A Guideline Development Group, consisting of ataxia specialist neurologists and representatives of Ataxia UK (including patients and carers), reviewed all sections, produced recommendations with levels of evidence, and discussed modifications (where necessary) with contributors until consensus was reached. Where no specific published data existed, recommendations were based on data related to similar conditions (e.g. multiple sclerosis) and/or expert opinion. The guidelines aim to assist HCPs when caring for patients with progressive ataxia, indicate evidence-based (where it exists) and best practice, and act overall as a useful resource for clinicians involved in managing ataxic patients. They do, however, also highlight the urgent need to develop effective disease-modifying treatments, and, given the large number of recommendations based on "good practice points", emphasise the need for further research to provide evidence for effective symptomatic therapies. These guidelines are aimed predominantly at HCPs in secondary care (such as general neurologists, clinical geneticists, physiotherapists, speech and language therapists, occupational therapists, etc.) who provide care for individuals with progressive ataxia and their families, and not ataxia specialists. It is a useful, practical tool to forward to HCPs at the time referrals are made for ongoing care, for example in the community.
Table S1. List of contributors. Table S2. Allied health professional interventions. Table S3. Pal... more Table S1. List of contributors. Table S2. Allied health professional interventions. Table S3. Palliative care. (DOCX 27 kb)
Dementia with Lewy Bodies (DLB) and Parkinson’s Disease Dementia (PDD) together, represent the se... more Dementia with Lewy Bodies (DLB) and Parkinson’s Disease Dementia (PDD) together, represent the second most common cause of dementia, after Alzheimer’s disease (AD). The synaptic dysfunctions underlying the cognitive decline and psychiatric symptoms observed throughout the development of PDD and DLB are still under investigation. In this study we examined the expression level of Dynamin1 and phospho-CaMKII, key proteins of endocytosis and synaptic plasticity respectively, as potential markers of molecular processes specifically deregulated with DLB and/or PDD. In order to measure the levels of these proteins, we isolated grey matter from post-mortem prefrontal cortex area (BA9), anterior cingulated gyrus (BA24) and parietal cortex (BA40) from DLB and PDD patients in comparison to age-matched controls and a group of AD cases. Clinical and pathological data available included the MMSE score, neuropsychiatric history, and semi-quantitative scores for AD pathology (plaques tangles) and f...
Background: The development of new therapies may rely on the conduct of human experimentation as ... more Background: The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. Methods: We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich’s Ataxia Research Alliance (FARA) sent the survey to their members. Responses were ana...