The Lessons OF RARE MALADIES.

Garrod, Archibald E.

doi:10.1016/s0140-6736(00)99941-0

Cited by 31 publications

(12 citation statements)

References 3 publications

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“…These findings linked the genetic cause of a rare form of PD with the inclusions in all cases of the disease. They were conceptually similar to those previously obtained in Alzheimer’s disease (AD) (Glenner and Wong 1984; Goate et al 1991) and some human tauopathies (Pollock et al 1986; Poorkaj et al 1998; Hutton et al 1998; Spillantini et al 1998a) and helped to underscore the view expressed by William Harvey (1578–1657) and reiterated by Archibald Garrod (1857–1936), that the study of rare forms of disease can inform the more common cases (Garrod 1928). In his letter of April 24, 1657, to John Vlackveld, Harvey wrote: “Nature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows traces of her workings apart from the beaten path; nor is there any better way to advance the proper practice of medicine than to give our minds to the discovery of the usual law of nature, by the careful investigation of cases of rarer forms of disease.” (Harvey and Willis 1847).…”

Section: Introductionmentioning

confidence: 95%

Neurodegeneration and the ordered assembly of α-synuclein

Spillantini

Goedert

2017

Cell Tissue Res

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In 2017, it was 200 years since James Parkinson published ‘An Essay on the Shaking Palsy’ and 20 years since α-synuclein aggregation came to the fore. In 1998, multiple system atrophy joined Parkinson’s disease and dementia with Lewy bodies as the third major synucleinopathy. Here, we describe the work that led to the identification of α-synuclein in Lewy bodies, Lewy neurites and Papp–Lantos bodies. We also review some of the findings reported since 1997.

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Section: Introductionmentioning

confidence: 95%

Neurodegeneration and the ordered assembly of α-synuclein

Spillantini

Goedert

2017

Cell Tissue Res

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“…The metabolic condition gists and technicians working on these problems and patients and their families awaiting therapies to improve their quality of life. I would like to conclude with two sentences who focused the attention on the study of rare diseases: the first is of W. The second is the title of a recent article by Talbot (13), "The study of rare diseases: butterfly collecting or an entrée to understanding common conditions?" .…”

Section: Problems Related To Therapy: the Example Of Cerebrotendinousmentioning

confidence: 99%

The Siena 25 Years Experience on Rare Neurological Diseases

Federico¹

2012

J Siena Acad Sci

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“…In fact, Sir Archibald Garrod FRS, the discoverer of the inborn errors of metabolism, was the first to popularize William Harvey's dictum about the value of 'careful investigation of rarer forms of disease' (Garrod 1928). This statement was itself a rare finding by Garrod as he was preparing to deliver the Harveian oration at the Royal College of Physicians in 1924 and as he read Harvey's correspondence (Willis 1848, p. 616).…”

Section: The Study Of Rare Variantsmentioning

confidence: 99%

Future perspectives for glycolipid research in medicine

Cox

2003

Phil. Trans. R. Soc. Lond. B

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Medical interest in glycolipids has been mainly directed to the rare and complex glycosphingolipid storage disorders that are principally caused by unitary deficiencies of lysosomal acid hydrolases. However, glycolipids are critical components of cell membranes and occur within newly described membrane domains known as lipid rafts. Glycolipids are components of important antigen systems and membrane receptors; they participate in intracellular signalling mechanisms and may be presented to the immune system in the context of the novel CD1 molecules present on T lymphocytes. A knowledge of their mechanism of action in the control of cell growth and survival as well as developmental pathways is likely to shed light on the pathogenesis of the glycosphingolipid storage disorders as well as the role of lipid second messengers in controlling cell mobility and in the mobilization of intracellular calcium stores (a biological role widely postulated particularly for the lysosphingolipid metabolite sphingosine 1-phosphate). Other sphingolipid metabolites such as ceramide 1-phosphate may be involved in apoptotic responses and in phagocytosis and synaptic vesicle formation. The extraordinary pharmaceutical success of enzymatic complementation for Gaucher's disease using macrophage-targeted human glucocerebrosidase has focused further commercial interest in other glycolipid storage diseases: the cost of targeted enzyme therapy and its failure to restore lysosomal enzymatic deficiencies in the brain has also stimulated interest in the concept of substrate reduction therapy using diffusible inhibitory molecules. Successful clinical trials of the iminosugar Nbutyldeoxynojirimycin in type 1 Gaucher's disease prove the principle of substrate reduction therapy and have attracted attention to this therapeutic method. They will also foster important further experiments into the use of glycolipid synthesis inhibitors for the severe neuronopathic glycosphingolipidoses, for which no definitive treatment is otherwise available. Future glycolipid research in medicine will be directed to experiments that shed light on the role of sphingolipids in signalling pathways, and in the comprehensive characterization and their secretory products in relation to the molecular pathogenesis of the storage disorders; experiments of use to improve the efficiency of complementing enzymatic delivery to the lysosomal compartment of storage cells are also needed. Further systematic screening for inhibitory compounds with specific actions in the pathways of glycosphingolipid biosynthesis will undoubtedly lead to clinical trials in the neuronopathic storage disorders and to wider applications in the fields of immunity and cancer biology.

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The Lessons OF RARE MALADIES.

Cited by 31 publications

References 3 publications

Neurodegeneration and the ordered assembly of α-synuclein

Neurodegeneration and the ordered assembly of α-synuclein

The Siena 25 Years Experience on Rare Neurological Diseases

Future perspectives for glycolipid research in medicine

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