scholarly journals Enhanced neuronal Met signalling levels in ALS mice delay disease onset

2011 ◽  
Vol 2 (3) ◽  
pp. e130-e130 ◽  
Author(s):  
M Genestine ◽  
E Caricati ◽  
A Fico ◽  
S Richelme ◽  
H Hassani ◽  
...  
Keyword(s):  
Disease Onset ◽  
Delay Disease Onset

scholarly journals Preclinical evaluation of a precision medicine approach to DNA vaccination in Type 1 diabetes

2021 ◽  
Author(s):  
Jorge Postigo Fernandez ◽  
Remi J Creusot
Keyword(s):  
Precision Medicine ◽  
Specific Immunotherapy ◽  
Dna Vaccines ◽  
Disease Onset ◽  
Delay Disease Onset ◽  
Intradermal Delivery ◽  
Dosing Frequency ◽  
Progression Of Disease

Antigen-specific immunotherapy involves the delivery of self-antigens as proteins or peptides (or using nucleic acids encoding them) to be presented with the goal of inducing tolerance. Approaches employing specific epitopes restricted to the subject's MHC haplotypes have multiplied and offer a more focused and tailored way of targeting autoreactive T cells. In addition, the Endotope platform allows endogenously expressed epitopes to be processed and presented on appropriate MHC class I and II molecules. Here, we evaluated the efficacy of a DNA vaccine encoding epitopes selected and tailored for the non-obese diabetic (NOD) mouse compared to the expression of the proinsulin protein, one of the most successful antigens in prevention of NOD disease, and we assessed the influence of several parameters (e.g. route, dosing frequency) on preventing diabetes onset at normoglycemic and dysglycemic stages. First, encoded peptides should be secreted for effective disease prevention. Furthermore, short weekly treatments with Endotope and proinsulin DNA vaccines delay disease onset, but sustained treatments are required for long-term protection, which was more significant with intradermal delivery. Although epitopes can be presented for at least two weeks, reducing the frequency of antigen administration from weekly to every other week reduced efficacy. Finally, both Endotope and proinsulin DNA vaccines were effective in the dysglycemic stage of disease, but proinsulin provided better protection, particularly in subjects with slower progression of disease. Thus, our data support the possibility of applying a precision medicine approach based on tailored epitopes for the treatment of tissue-specific autoimmune diseases with DNA vaccines.

The antioxidantN-acetylcysteine does not delay disease onset and death in a transgenic mouse model of amyotrophic lateral sclerosis

1998 ◽  
Vol 44 (2) ◽  
pp. 293-293 ◽  
Author(s):  
Dick Jaarsma ◽  
Henk-Jan Guchelaar ◽  
Elize Haasdijk ◽  
J. M. B. Vianney de Jong ◽  
Jan C. Holstege
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Disease Onset ◽  
Transgenic Mouse Model ◽  
Delay Disease Onset ◽  
Lateral Sclerosis

scholarly journals Evaluation of drugs for treatment of prion infections of the central nervous system

2008 ◽  
Vol 89 (2) ◽  
pp. 594-597 ◽  
Author(s):  
Constanze Riemer ◽  
Michael Burwinkel ◽  
Anja Schwarz ◽  
Sandra Gültner ◽  
Simon W. F. Mok ◽  
...  
Keyword(s):  
Prion Diseases ◽  
Disease Onset ◽  
Therapeutic Benefit ◽  
High Dose ◽  
Therapeutic Approaches ◽  
Minocycline Treatment ◽  
Delay Disease Onset ◽  
The Central Nervous System ◽  
Pass Through ◽  
Lateral Sclerosis

Prion diseases are fatal and at present there are neither cures nor therapies available to delay disease onset or progression in humans. Inspired in part by therapeutic approaches in the fields of Alzheimer's disease and amyotrophic lateral sclerosis, we tested five different drugs, which are known to efficiently pass through the blood–brain barrier, in a murine prion model. Groups of intracerebrally prion-challenged mice were treated with the drugs curcumin, dapsone, ibuprofen, memantine and minocycline. Treatment with antibiotics dapsone and minocycline had no therapeutic benefit. Ibuprofen-treated mice showed severe adverse effects, which prevented assessment of therapeutic efficacy. Mice treated with low- but not high-dose curcumin and mice treated with memantine survived infections significantly longer than untreated controls (P<0.01). These results encourage further research efforts to improve the therapeutic effect of these drugs.

scholarly journals Lifetime risk of common neurological diseases in the elderly population

2018 ◽  
Vol 90 (2) ◽  
pp. 148-156 ◽  
Author(s):  
Silvan Licher ◽  
Sirwan K L Darweesh ◽  
Frank J Wolters ◽  
Lana Fani ◽  
Alis Heshmatollah ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Disease Onset ◽  
Population Level ◽  
The Elderly ◽  
Population Based ◽  
Lifetime Risk ◽  
Ageing Population ◽  
Preventive Strategies ◽  
Delay Disease Onset

ObjectiveTo quantify the burden of common neurological disease in older adults in terms of lifetime risks, including their co-occurrence and preventive potential, within a competing risk framework.MethodsWithin the prospective population-based Rotterdam Study, we studied lifetime risk of dementia, stroke and parkinsonism between 1990 and 2016. Among 12 102 individuals (57.7% women) aged ≥45 years free from these diseases at baseline, we studied co-occurrence, and quantified the combined, and disease-specific remaining lifetime risk of these diseases at various ages for men and women separately. We also projected effects on lifetime risk of hypothetical preventive strategies that delay disease onset by 1, 2 and 3 years, respectively.ResultsDuring follow-up of up to 26 years (156 088 person-years of follow-up), 1489 individuals were diagnosed with dementia, 1285 with stroke and 263 with parkinsonism. Of these individuals, 438 (14.6%) were diagnosed with multiple diseases. Women were almost twice as likely as men to be diagnosed with both stroke and dementia during their lifetime. The lifetime risk for any of these diseases at age 45 was 48.2% (95% CI 47.1% to 51.5%) in women and 36.2% (35.1% to 39.3%) in men. This difference was driven by a higher risk of dementia as the first manifesting disease in women than in men (25.9% vs 13.7%; p<0.001), while this was similar for stroke (19.0%vs18.9% in men) and parkinsonism (3.3% vs 3.6% in men). Preventive strategies that delay disease onset with 1 to 3 years could theoretically reduce lifetime risk for developing any of these diseases by 20%–50%.ConclusionOne in two women and one in three men will develop dementia, stroke or parkinsonism during their life. These findings strengthen the call for prioritising the focus on preventive interventions at population level which could substantially reduce the burden of common neurological diseases in the ageing population.

Magnesium supplementation does not delay disease onset or increase survival in a mouse model of familial ALS

2003 ◽  
Vol 216 (1) ◽  
pp. 95-98 ◽  
Author(s):  
Roger Pamphlett ◽  
Elizabeth Todd ◽  
Robert Vink ◽  
Robert McQuilty ◽  
Surindar S Cheema
Keyword(s):  
Mouse Model ◽  
Disease Onset ◽  
Magnesium Supplementation ◽  
Delay Disease Onset ◽  
Familial Als

scholarly journals Genetic Variations and mRNA Expression of NRF2 in Parkinson’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Caroline Ran ◽  
Karin Wirdefeldt ◽  
Lovisa Brodin ◽  
Mehrafarin Ramezani ◽  
Marie Westerlund ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mrna Expression ◽  
Age Of Onset ◽  
Human Lymphocytes ◽  
Disease Onset ◽  
Cellular Protection ◽  
Expression Levels ◽  
Reverse Transcription Pcr ◽  
Delay Disease Onset

Nuclear factor erythroid 2-like 2 (NRF2) encodes a transcription factor regulating mechanisms of cellular protection and is activated by oxidative stress. NRF2 has therefore been hypothesized to confer protection against Parkinson’s disease and so far an NRF2 haplotype has been reported to decrease the risk of developing disease and delay disease onset. Also NRF2 adopts a nuclear localization in Parkinson’s disease, which is indicative of increased NRF2 activity. We have investigated the association between NRF2 and Parkinson’s disease in a Swedish case-control material and whether NRF2 expression levels correlate with NRF2 genetic variants, disease, or disease onset. Using pyrosequencing, we genotyped one intronic and three promoter variants in 504 patients and 509 control subjects from Stockholm. Further, we quantified NRF2 mRNA expression in EBV transfected human lymphocytes from patients and controls using quantitative real-time reverse transcription PCR. We found that one of the promoter variants, rs35652124, was associated with age of disease onset (Χ2 = 14.19, p value = 0.0067). NRF2 mRNA expression levels however did not correlate with the rs35652124 genotype, Parkinson’s disease, or age of onset in our material. More detailed studies on NRF2 are needed in order to elucidate how this gene affects pathophysiology of Parkinson’s disease.

scholarly journals Interruptions of the FXN GAA Repeat Tract Delay the Age at Onset of Friedreich’s Ataxia in a Location Dependent Manner

2021 ◽  
Vol 22 (14) ◽  
pp. 7507
Author(s):  
Suran Nethisinghe ◽  
Maheswaran Kesavan ◽  
Heather Ging ◽  
Robyn Labrum ◽  
James M. Polke ◽  
...  
Keyword(s):  
Trinucleotide Repeat ◽  
Age At Onset ◽  
Disease Onset ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Dependent Manner ◽  
Repeat Tract ◽  
Delay Disease Onset ◽  
Intron 1 ◽  
Exponential Decay Model

Friedreich’s ataxia (FRDA) is a comparatively rare autosomal recessive neurological disorder primarily caused by the homozygous expansion of a GAA trinucleotide repeat in intron 1 of the FXN gene. The repeat expansion causes gene silencing that results in deficiency of the frataxin protein leading to mitochondrial dysfunction, oxidative stress and cell death. The GAA repeat tract in some cases may be impure with sequence variations called interruptions. It has previously been observed that large interruptions of the GAA repeat tract, determined by abnormal MboII digestion, are very rare. Here we have used triplet repeat primed PCR (TP PCR) assays to identify small interruptions at the 5′ and 3′ ends of the GAA repeat tract through alterations in the electropherogram trace signal. We found that contrary to large interruptions, small interruptions are more common, with 3′ interruptions being most frequent. Based on detection of interruptions by TP PCR assay, the patient cohort (n = 101) was stratified into four groups: 5′ interruption, 3′ interruption, both 5′ and 3′ interruptions or lacking interruption. Those patients with 3′ interruptions were associated with shorter GAA1 repeat tracts and later ages at disease onset. The age at disease onset was modelled by a group-specific exponential decay model. Based on this modelling, a 3′ interruption is predicted to delay disease onset by approximately 9 years relative to those lacking 5′ and 3′ interruptions. This highlights the key role of interruptions at the 3′ end of the GAA repeat tract in modulating the disease phenotype and its impact on prognosis for the patient.

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