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- Björklund, Anders, 1950-
(författare)
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Intergenerational inequalities across different outcomes : comments from an economist
- 2024
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Ingår i: Research handbook on intergenerational inequality. - : Edward Elgar Publishing. - 9781800888258 - 9781800888265
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Bokkapitel (refereegranskat)abstract
- This chapter discusses the state of the intergenerational income mobility literature from the beginning of the 1990s, when new influential papers spurred the interest in studying this kind of mobility in a large number of countries. The academic interaction between this new literature and the more established class mobility approach in sociology is also discussed. In a concluding section of the chapter, two important tasks for future research are stressed. First, it is important to consider the specific concept of income used in the studies. Such concepts also change over time and from one generation to the next. Second, the relationship to the fundamental goal of equality of opportunity can be strengthened by considering the broader role of family and community background.
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- Björklund, Anders, et al.
(författare)
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The basal forebrain cholinergic system as target for cell replacement therapy in Parkinson's disease
- 2024
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Ingår i: Brain. - 0006-8950. ; 147:6, s. 1937-1952
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Forskningsöversikt (refereegranskat)abstract
- In recent years there has been a renewed interest in the basal forebrain cholinergic system as a target for the treatment of cognitive impairments in patients with Parkinson's disease, due in part to the need to explore novel approaches to treat the cognitive symptoms of the disease and in part to the development of more refined imaging tools that have made it possible to monitor the progressive changes in the structure and function of the basal forebrain system as they evolve over time. In parallel, emerging technologies allowing the derivation of authentic basal forebrain cholinergic neurons from human pluripotent stem cells are providing new powerful tools for the exploration of cholinergic neuron replacement in animal models of Parkinson's disease-like cognitive decline. In this review, we discuss the rationale for cholinergic cell replacement as a potential therapeutic strategy in Parkinson's disease and how this approach can be explored in rodent models of Parkinson's disease-like cognitive decline, building on insights gained from the extensive animal experimental work that was performed in rodent and primate models in the 1980s and 90s. Although therapies targeting the cholinergic system have so far been focused mainly on patients with Alzheimer's disease, Parkinson's disease with dementia may be a more relevant condition. In Parkinson's disease with dementia, the basal forebrain system undergoes progressive degeneration and the magnitude of cholinergic cell loss has been shown to correlate with the level of cognitive impairment. Thus, cell therapy aimed to replace the lost basal forebrain cholinergic neurons represents an interesting strategy to combat some of the major cognitive impairments in patients with Parkinson's disease dementia.
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- Barker, Roger A., et al.
(författare)
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Restorative cell and gene therapies for Parkinson's disease
- 2023
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Ingår i: Precision Medicine in Neurodegenerative Disorders, Part II. - 0072-9752 .- 2212-4152. - 9780323855556 ; 193, s. 211-226
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Bokkapitel (refereegranskat)abstract
- One of the core pathological features of Parkinson's disease (PD) is the loss of the dopaminergic nigrostriatal pathway which lies at the heart of many of the motor features of this condition as well as some of the cognitive problems. The importance of this pathological event is evident through the clinical benefits that are seen when patients with PD are treated with dopaminergic agents, at least in early-stage disease. However, these agents create problems of their own through stimulation of more intact dopaminergic networks within the central nervous system causing major neuropsychiatric problems including dopamine dysregulation. In addition, over time the nonphysiological stimulation of striatal dopamine receptors by L-dopa containing drugs leads to the genesis of L-dopa-induced dyskinesias that can become very disabling in many cases. As such, there has been much interest in trying to better reconstitute the dopaminergic nigrostriatal pathway using either factors to regrow it, cells to replace it, or gene therapies to restore dopamine transmission in the striatum. In this chapter, we lay out the rationale, history and current status of these different therapies as well as highlighting where the field is heading and what new interventions might come to clinic in the coming years.
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- Kirkeby, Agnete, et al.
(författare)
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Preclinical quality, safety, and efficacy of a human embryonic stem cell-derived product for the treatment of Parkinson's disease, STEM-PD
- 2023
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Ingår i: Cell Stem Cell. - 1934-5909. ; 30:10, s. 1299-1314
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Tidskriftsartikel (refereegranskat)abstract
- Cell replacement therapies for Parkinson's disease (PD) based on transplantation of pluripotent stem cell-derived dopaminergic neurons are now entering clinical trials. Here, we present quality, safety, and efficacy data supporting the first-in-human STEM-PD phase I/IIa clinical trial along with the trial design. The STEM-PD product was manufactured under GMP and quality tested in vitro and in vivo to meet regulatory requirements. Importantly, no adverse effects were observed upon testing of the product in a 39-week rat GLP safety study for toxicity, tumorigenicity, and biodistribution, and a non-GLP efficacy study confirmed that the transplanted cells mediated full functional recovery in a pre-clinical rat model of PD. We further observed highly comparable efficacy results between two different GMP batches, verifying that the product can be serially manufactured. A fully in vivo-tested batch of STEM-PD is now being used in a clinical trial of 8 patients with moderate PD, initiated in 2022.
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- Mattsson, Bengt, et al.
(författare)
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Athymic Nude Rat Brain Atlas
- 2023
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Bok (refereegranskat)abstract
- Athymic Nude Rat Brain Atlas will provide the first stereotaxic brain atlas of the athymic nude rat (Crl:NIH-Foxn1rnu), a T-cell deficient rat model commonly used in experimental studies and pre-clinical safety and efficacy studies. This 2D vector-based atlas contains coronal, sagittal, and horizontal brain sections of an athymic rat brain rendered from a single cleared specimen, placed in a computerized 3D environment. The maps enable readers to better calculate co-ordinates to target specific structures for toxin, virus, or cell delivery using stereotaxic surgery. This atlas will be a valuable resource for any neuroscientist who wishes to work with nude rats in experimental and pre-clinical studies.
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- Björklund, Anders, et al.
(författare)
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A Combined α-Synuclein/Fibril (SynFib) Model of Parkinson-Like Synucleinopathy Targeting the Nigrostriatal Dopamine System
- 2022
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Ingår i: Journal of Parkinson's Disease. - 1877-718X. ; 12:8, s. 2307-2320
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Forskningsöversikt (refereegranskat)abstract
- Injections of pre-formed α-synuclein fibrils (PFFs) or overexpression of α-synuclein using AAV vectors are commonly used as models of Parkinson-like synucleinopathy in rats and mice. In the modified method reviewed here, the "SynFib" model, the PFFs and the AAV vector are administered together unilaterally into the substantia nigra. This approach combines the key features of these two models, i.e., the generation of toxic α-synuclein aggregates and Lewy body-like inclusions, in combination with the increased vulnerability caused by increased cellular levels of α-synuclein. The combined AAV/PFF delivery offers several advantages over the standard PFF model due to the enhanced and accelerated α-synuclein pathology and microglial response induced by the PFF seeds in the presence of an elevated α-synuclein level. Injection of the AAV/PFF mixture into the substantia nigra makes it possible to target a larger proportion of the nigral dopamine neurons and obtain a level of dopamine cell loss (>60%) needed to induce significant impairments in drug-induced and spontaneous motor tests. The SynFib model shares attractive features of the standard 6-OHDA lesion model: a single unilateral stereotaxic intervention; pathology and cell loss developing over a short time span; and the possibility to monitor the degenerative changes using tests of motor behavior.
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- Björklund, Anders, 1950-, et al.
(författare)
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Fördelningsdebatten inför valet 2022– centrala frågor och försök till svar
- 2022
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Ingår i: Ekonomisk Debatt. - 0345-2646. ; 50:3, s. 5-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Frågor om inkomst- och förmögenhetsskillnader får stort utrymme i den poli-tiska debatten och kan bli viktiga under valrörelsen 2022. I denna artikelgranskar vi ett antal återkommande påståenden om Sveriges inkomstfördel-ning och finner att de ofta är överdrivna och ibland direkt felaktiga. Det gällerbl a Sveriges position i världens jämlikhetsliga, nivån på inkomstskillnaderna,kapitalinkomsternas betydelse och den ekonomiska politikens inverkan övertid. Vi pekar även ut ett antal brister i den officiella inkomststatistiken och dis-kuterar hur den kan förbättras.
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