PRION DISEASE UPDATE 2010 (10)

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[With the continuing decline of the number of cases in the human
population of variant Creutzfeldt-Jakob disease -- abbreviated
previously as vCJD or CJD (new var.) in ProMED-mail -- it has been
decided to broaden the scope of the occasional ProMED-mail updates to
include other prion-related diseases. In addition to vCJD, data on
other forms of CJD: sporadic, iatrogenic, familial, and GSS
(Gerstmann-Straussler-Scheinker disease) are included also since they
may have some relevance to the incidence and etiology of vCJD. - Mod.CP]

In this update:
[1] UK: National CJD Surveillance Unit - monthly statistics as of Mon
1 Nov 2010 - no new vCJD cases
[2] France: Institut de Veille Sanitaire - monthly statistics as of
Fri 29 Oct 2010 - no new vCJD cases
[3] USA: National Prion Disease Pathology Surveillance Center - data
not updated since 31 Jul 2010, no indigenous vCJD
[4] Prion disease susceptibility

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[1] UK: National CJD Surveillance Unit - monthly statistics as of Mon
1 Nov 2010 - no new vCJD cases
Date: Mon 1 Nov 2010
Source: UK National CJD Surveillance Unit, monthly statistics [edited]



The number of deaths due to definite or probable vCJD cases remains
170. A total of 4 definite/probable patients are still alive so the
total number of definite or probable vCJD cases remains 174.

Although 3 new deaths due to vCJD were recorded in 2009 and now 3
deaths in 2010 so far, the overall picture is still consistent with
the view that the vCJD outbreak in the UK is in decline, albeit now
with a pronounced tail. The 1st cases were observed in 1995, and the
peak number of deaths was 28 in the year 2000, followed by 20 in
2001, 17 in 2002, 18 in 2003, 9 in 2004, 5 in 2005, 5 in 2006, 5 in
2007, one in 2008, 3 in 2009, and now 3 so far in 2010.

Totals for all types of CJD cases in the UK so far in the year 2010
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During the 1st 10 months of 2010, there have been 126 referrals, 54
fatal cases of sporadic CJD, 3 fatal cases of vCJD, 2 cases of
iatrogenic CJD, 2 cases of familial CJD, and one case of GSS.

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[2] France: Institut de Veille Sanitaire - monthly statistics as of
Fri 29 Oct 2010 - no new vCJD cases
Date: Fri 5 Nov 2010
Source: IVS - Maladie de Creutzfeldt-Jakob et maladies apparentees
[in French, trans. & summ. Mod.CP, edited]



During the 1st 10 months of 2010, there were 1332 referrals, 75
confirmed cases of sporadic CJD, 4 cases of familial CJD, and no
cases of iatrogenic CJD or vCJD.

A total of 25 cases of confirmed or probable vCJD have been recorded
in France since records began in 1992. There was 1 case in 1996, 1 in
2000, 1 in 2001, 3 in 2002, 2 in 2004, 6 in 2005, 6 in 2006, 3 in
2007, 2 in 2009, and none so far in 2010.

The 25 confirmed cases comprise 13 females and 12 males. All 25 are
now deceased. Their median age is 37 (between 19 and 58). 7 were
resident in the Ile-de-France and 18 in the provinces. All the
identified cases have been Met-Met homozygotes. No risk factor has
been identified. One of the 25 had made frequent visits to the United
Kingdom, during about 10 years from 1987.

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[3] USA: National Prion Disease Pathology Surveillance Center - data
not updated since 31 Jul 2010, no indigenous vCJD
Date: Fri 5 Nov 2010
Source: US National Prion Disease Pathology Surveillance Center [edited]



No update since 31 Jul 2010.

During the 7 month period 1 Jan 2010 to 31 Jul 2010, there were 204
referrals, 124 of whom were classified as prion disease, comprising
85 cases of sporadic CJD, 20 of familial CJD, and no cases of
iatrogenic CJD or vCJD.

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[4] Prion disease susceptibility
Date: Mon 1 Nov 2010
Source: Proceedings of the National Academy of Sciences of the USA
(PNAS) [edited]



Ref: MQ Khan, B Sweeting, VK Mulligan, et al: Prion disease
susceptibility is affected by beta-structure folding propensity and
local side-chain interactions in PrP. Proc Natl Acad Sci USA 2010
(Epub ahead of print); doi:10.1073/pnas.1005267107
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Abstract
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Prion diseases occur when the normally alpha-helical prion protein
(PrP) converts to a pathological beta-structured state with prion
infectivity (PrPSc). Exposure to PrPSc from other mammals can
catalyze this conversion. Evidence from experimental and accidental
transmission of prions suggests that mammals vary in their prion
disease susceptibility: hamsters and mice show relatively high
susceptibility, whereas rabbits, horses, and dogs show low susceptibility.

Using a novel approach to quantify conformational states of PrP by
circular dichroism (CD), we find that prion susceptibility tracks
with the intrinsic propensity of mammalian PrP to convert from the
native, alpha-helical state to a cytotoxic beta-structured state,
which exists in a monomer-octamer equilibrium. It has been
controversial whether beta-structured monomers exist at acidic pH;
sedimentation equilibrium and dual-wavelength CD evidence is
presented for an equilibrium between a beta-structured monomer and
octamer in some acidic pH conditions.

Our X-ray crystallographic structure of rabbit PrP has identified a
key helix-capping motif implicated in the low prion disease
susceptibility of rabbits. Removal of this capping motif increases
the beta-structure folding propensity of rabbit PrP to match that of
PrP from mouse, a species more susceptible to prion disease.

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[This research provides a physical explanation of how changes in the
structure of the prion protein can affect the prion disease
susceptibility of different mammals. - Mod.CP]

[see also:
Prion disease update 2010 (09) 20101006.3622
Prion disease update 2010 (08) 20100911.3285
Prion disease update 2010 (07) 20100809.2720
Prion disease update 2010 (06) 20100706.2248
Prion disease update 2010 (05) 20100507.1488
Prion disease update 2010 (04) 20100405.1091
Prion disease update 2010 (03) 20100304.0709
Prion disease update 2010 (02) 20100205.0386
Prion disease update 2010 20100107.0076]
...................................cp/mj/mpp

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