| 1. |
- Björklund, Anders, et al.
(författare)
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Gene therapy for dopamine replacement in Parkinson's disease.
- 2009
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 1:2, s. 2-2
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of L-dopa (L-3,4-dihydroxyphenylalanine) therapy 40 years ago was a revolution in the treatment of patients with Parkinson s disease (PD). With time, however, the shortcomings of oral L-dopa medication became apparent, in particular the appearance of troublesome side effects, expressed as involuntary movements (dyskinesias) that developed over time in many patients. A gene therapy approach, aimed at restoring dopamine synthesis in the affected brain by viral vector delivery of genes that encode the dopamine-synthesizing enzymes, may offer a solution to this problem. Now, a team of French and UK researchers reports promising results in a nonhuman primate model of PD, paving the way for clinical trials of this enzyme-replacement approach.
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| 2. |
- Björklund, Anders, et al.
(författare)
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Gene therapy for Parkinson's disease shows promise.
- 2011
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 3:79, s. 1-79
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Tidskriftsartikel (refereegranskat)abstract
- A gene therapy trial for Parkinson's disease met its primary endpoint, but challenges remain.
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| 3. |
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| 4. |
- Finnveden, Göran, et al.
(författare)
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Policy instruments towards a sustainable waste management
- 2013
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Ingår i: Sustainability. - Basel : MDPI AG. - 2071-1050. ; 5:3, s. 841-881
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this paper is to suggest and discuss policy instruments that could lead towards a more sustainable waste management. The paper is based on evaluations from a large scale multi-disciplinary Swedish research program. The evaluations focus on environmental and economic impacts as well as social acceptance. The focus is on the Swedish waste management system but the results should be relevant also for other countries. Through the assessments and lessons learned during the research program we conclude that several policy instruments can be effective and possible to implement. Particularly, we put forward the following policy instruments: “Information”; “Compulsory recycling of recyclable materials”; “Weight-based waste fee in combination with information and developed recycling systems”; “Mandatory labeling of products containing hazardous chemicals”, “Advertisements on request only and other waste minimization measures”; and “Differentiated VAT and subsidies for some services”. Compulsory recycling of recyclable materials is the policy instrument that has the largest potential for decreasing the environmental impacts with the configurations studied here. The effects of the other policy instruments studied may be more limited and they typically need to be implemented in combination in order to have more significant impacts. Furthermore, policy makers need to take into account market and international aspects when implementing new instruments. In the more long term perspective, the above set of policy instruments may also need to be complemented with more transformational policy instruments that can significantly decrease the generation of waste.
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| 5. |
- Finnveden, Göran, et al.
(författare)
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Policy Instruments towards a sustainable waste management
- 2016
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Ingår i: Solid waste management: Policy and planning for a sustainable society. - : Apple Academic Press. - 9781771883740 - 9780429091650 ; , s. 185-246, s. 185-246
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Parmar, Malin, et al.
(författare)
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In vivo conversion of dopamine neurons in mouse models of Parkinson's disease - a future approach for regenerative therapy?
- 2021
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Ingår i: Current Opinion in Genetics & Development. - : Elsevier BV. - 1879-0380 .- 0959-437X. ; 70, s. 76-82
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Forskningsöversikt (refereegranskat)abstract
- Recent advances in cell reprogramming have made it possible to form new therapeutic cells within the body itself via a process called direct conversion or lineage reprogramming. A series of studies have shown that it is possible to reprogram resident glia into new neurons within the brain parenchyma. These studies opened up for the targeted attempts to achieve functional brain repair using in vivo conversion. Because of the relatively focal degeneration, Parkinson's Disease (PD) is an attractive target for both transplantation-based and in vivo conversion-based reparative approaches. Fetal cell transplants have provided proof-of-concept and stem cell-based therapies for PD are now on the verge of entering clinical trials. In the future, in vivo conversion may be an alternative to transplantation-based therapies.
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| 7. |
- Rosenblad, Carl, et al.
(författare)
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Vector-mediated l-3,4-dihydroxyphenylalanine delivery reverses motor impairments in a primate model of Parkinson's disease
- 2019
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; , s. 2402-2416
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Tidskriftsartikel (refereegranskat)abstract
- Ever since its introduction 40 years ago l-3,4-dihydroxyphenylalanine (l-DOPA) therapy has retained its role as the leading standard medication for patients with Parkinson's disease. With time, however, the shortcomings of oral l-DOPA treatment have become apparent, particularly the motor fluctuations and troublesome dyskinetic side effects. These side effects, which are caused by the excessive swings in striatal dopamine caused by intermittent oral delivery, can be avoided by delivering l-DOPA in a more continuous manner. Local gene delivery of the l-DOPA synthesizing enzymes, tyrosine hydroxylase and guanosine-tri-phosphate-cyclohydrolase-1, offers a new approach to a more refined dopaminergic therapy where l-DOPA is delivered continuously at the site where it is needed i.e. the striatum. In this study we have explored the therapeutic efficacy of adeno-associated viral vector-mediated l-DOPA delivery to the putamen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated rhesus monkeys, the standard non-human primate model of Parkinson's disease. Viral vector delivery of the two enzymes, tyrosine hydroxylase and guanosine-5'-tri-phosphate-cyclohydrolase-1, bilaterally into the dopamine-depleted putamen, induced a significant, dose-dependent improvement of motor behaviour up to a level identical to that obtained with the optimal dose of peripheral l-DOPA. Importantly, this improvement in motor function was obtained without any adverse dyskinetic effects. These results provide proof-of-principle for continuous vector-mediated l-DOPA synthesis as a novel therapeutic strategy for Parkinson's disease. The constant, local supply of l-DOPA obtained with this approach holds promise as an efficient one-time treatment that can provide long-lasting clinical improvement and at the same time prevent the appearance of motor fluctuations and dyskinetic side effects associated with standard oral dopaminergic medication.
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| 8. |
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| 9. |
- Ahlgren, Serina, et al.
(författare)
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Review of methodological choices in LCA of biorefinery systems - key issues and recommendations
- 2015
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Ingår i: Biofuels, Bioproducts and Biorefining. - : Wiley. - 1932-1031 .- 1932-104X. ; 9:5, s. 606-619
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Forskningsöversikt (refereegranskat)abstract
- The current trend in biomass conversion technologies is toward more efficient utilization of biomass feedstock in multiproduct biorefineries. Many life-cycle assessment (LCA) studies of biorefinery systems have been performed but differ in how they use the LCA methodology. Based on a review of existing LCA standards and guidelines, this paper provides recommendations on how to handle key methodological issues when performing LCA studies of biorefinery systems. Six key issues were identified: (i) goal definition, (ii) functional unit, (iii) allocation of biorefinery outputs, (iv) allocation of biomass feedstock, (v) land use, and (vi) biogenic carbon and timing of emissions. Many of the standards and guidelines reviewed here provide only general methodological recommendations. Some make more specific methodological recommendations, but these often differ between standards. In this paper we present some clarifications (e.g. examples of research questions and suitable functional units) and methodological recommendations (e.g. on allocation).
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| 10. |
- Aldrin-Kirk, Patrick, et al.
(författare)
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A novel two-factor monosynaptic TRIO tracing method for assessment of circuit integration of hESC-derived dopamine transplants
- 2022
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Ingår i: Stem Cell Reports. - : Elsevier BV. - 2213-6711. ; 17:1, s. 159-172
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Tidskriftsartikel (refereegranskat)abstract
- Transplantation in Parkinson's disease using human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons is a promising future treatment option. However, many of the mechanisms that govern their differentiation, maturation, and integration into the host circuitry remain elusive. Here, we engrafted hESCs differentiated toward a ventral midbrain DA phenotype into the midbrain of a preclinical rodent model of Parkinson's disease. We then injected a novel DA-neurotropic retrograde MNM008 adeno-associated virus vector capsid, into specific DA target regions to generate starter cells based on their axonal projections. Using monosynaptic rabies-based tracing, we demonstrated for the first time that grafted hESC-derived DA neurons receive distinctly different afferent inputs depending on their projections. The similarities to the host DA system suggest a previously unknown directed circuit integration. By evaluating the differential host-to-graft connectivity based on projection patterns, this novel approach offers a tool to answer outstanding questions regarding the integration of grafted hESC-derived DA neurons.
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