Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1997-02-25
1998-05-05
Jones, W. Gary
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435 71, 435 72, 435 79, 435 912, 5303882, 436500, 424 88, 536 231, 536 243, 536 2433, C12Q 168, C12P 1934, C07H 2102, C07H 2104
Patent
active
057472602
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to methods of prognosing the likelihood of neurodegenerative pathology and dementia in head-injured patients.
Accidental or non-accidental head injuries are common events. The precise number of patients suffering a head injury are difficult to calculate exactly since the methods of defining and counting cases varies from country to country. However the relevant figures for the UK serve as a useful guide to the extent of the problem. In the UK some 300 persons per 100,000 of the population are admitted to hospital each year as a result of head injury. Of these patients 9 per 100,000 will die as a direct result of the severity of their injuries. Outcome surveys in the USA indicate that for every 100 head injury survivors up to 5 remain in a coma, up to 15 are still severly disabled six months after injury, 20 have minor psychiatric or psychological problems and the remaining 60 will make a good recovery. These figures give rise to an estimated population of some 500,000 persons in the USA who have a persisting handicap as a result of trauma related head injury. The social and economic cost of dealing with the after effects of such injuries is large.sup.1,2,3,4.
The cause of this problem is the brain damage that occurs in up to 30% of patients who are admitted to hospital with a head injury.sup.4. The damage arises from the physical effects of the trauma (such as swelling, herniation, haemorrhage, global or focal damage or compromise of the vascular supply, contusion, cranial and peripheral nerve damage, axonal injury and embolism.sup.3,4,5,6) and also from the neurochemical consequences of the ischaemia which invariably accompanies physical brain damage.sup.3,4,5,6. Such injuries and subsequent damage are often widespread and can involve regions of the spinal cord, cranial and peripheral nerves in addition to the brain.sup.1,3,4.
In addition the brain damage caused by head injury also produces the risk of subsequent psychiatric and neurologic complications including epilepsy and chronic neuro-degenerative states (eg dementia pugilistica or punch drunk syndrome).sup.3,4,5,6,7,8,9,10,11.
The extent of brain damage caused by a head injury can vary markedly from patient to patient Thus, the likelihood and degree of sustaining pathological brain damage in the immediate aftermath of the trauma and the risk of subsequent chronic neurodegeneration leading to epilepsy or a dementing condition vary also.
The pathophysiology of head injury has been investigated in an effort to determine the molecular mechanisms which enable the acute triggering event of a head injury to be transformed into a chronic neurodegenerative pathological process.sup.12,13,14,15.
Head-injured patients show increased levels of .beta. amyloid precursor protein immunoreactivity.sup.14 and some 30% of head injured patients have evidence of .beta. amyloid protein deposition.sup.15. This deposition can occur within days of a single head injury. The eventual consequence of substantial numbers of .beta. amyloid deposits is the emergence of a clinical syndrome of cognitive decline and increasing dementia.sup.3,8. Such deposits have been shown to be present in a number of dementing syndromes and these include Alzheimer's disease, cortical Lewy body disease, Parkinson's disease and the Alzheimer-type disease in patients with Down's syndrome.sup.3. In addition .beta. amyloid deposits are present in the brains of patients with vascular and cerebrovascular disease and these latter conditions can predispose or contribute to the above diseases.sup.3.
Recently, the apolipoprotein E (ApoE) genotype has been shown to be an important determinant in the etiology of AD.sup.16-23 with the presence and number of E4 alleles being associated with increased risk and earlier ages of onset of disease in both familial cases linked to chromosome 19 and sporadic cases. The presence of E2 alleles has been claimed to decrease the risk (be `protective`) of late onset Alzheimer disease.sup.18,19,24. This inference is based on the increased frequency
REFERENCES:
Vanderputten. Disseration Abstracts International, 1 Oct. 1993, vol. 54, No. 4, Identification and characterization of apolipoprotein E in human neurodegeneration, .
Roberts et al. Journal of Neurology, Neurosurgery and Psychiatry, Jan. 1994, vol. 57, pp. 419-425.
Nicoll et al. Nature Medicine, 1995, vol. 1 No. 2, pp. 135-137.
Graham David Ian
Nicoll James Alan Ramsey
Roberts Gareth Wyn
Jones W. Gary
Kanagy James M.
Lentz Edward T.
Rees Dianne
SmithKline Beecham p.l.c.
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