Possible transfusion transmitted cerebral amyloid angiopathy: evaluation of transmission of AΒ using the radar repository
Ended Project Grant Awarded Last action
- Award ID
- R21HL175170
- Recipient
-
Vitalant UEI GKT4L2JZJ622
- Awarding agency
-
National Heart Lung and Blood Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $262,500
Award facts
- Assistance listing
- 93.837 Cardiovascular Diseases Research
- Completion date
- Place of performance
- San Francisco, CA 94105, USA
Award details come from USAspending.gov.
Description
- Abstract
- Cerebral amyloid angiopathy (CAA) is a common cause of spontaneous intracerebral hemorrhage (ICH), with a case fatality rate of 30-50%. CAA is characterized by aggregation of likely misfolded deposits of amyloid Β (AΒ) in the cerebral vasculature, leading to vascular weakening and repeated, unprovoked ICH. Over the past decade evidence has been accumulating that AΒ exhibits prion-like properties, being overtly transmissible in experimental settings through a range of different parenteral routes. More pressingly, still, parenteral iatrogenic AΒ transmissibility, leading to CAA development, has also been demonstrated in humans, following neurosurgery and in patients treated with cadaveric human growth hormone. Given that prions are readily transfusion transmissible, this raises the disconcerting possibility that CAA and its related AΒ-associated conditions, are potentially transfusion transmissible. A large, BI-national, retrospective cohort study using the swedish-danish scandat transfusion database found that 0.1% of transfused patients in sweden and denmark received red- cell units from blood donors who later suffered repeated, unprovoked ICH, and that these patients were at a near-3-fold increased risk of themselves suffering an unprovoked ICH, as compared to patients who did not receive red-cell units from affected blood donors. Under the hypothesis that the observed association was driven by AΒ transmission and CAA development in affected donors and recipients, the clinical implications could be very large, especially considering that AΒ aggregation is also strongly associated with alzheimer's disease. However, external replication of these preliminary findings, ideally with biochemical and mechanistic corroboration, is urgently needed. We therefore propose to utilize the existing nhlbi reds allogeneic donor and recipient (RADAR) repository, with samples from both blood donors and pre- and post- transfusion samples of transfused, to (a) investigate the prevalence of amyloid Β pathology through measures of the associated PTAU217 protein among blood donors, and (B) investigate the possibility that amyloid Β is transfusion- transmissible from affected donors to their transfused patients.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $131,250 | |
| Amendment | $12,525 | |
| Original award | $118,725 |
Quick answers
Who received award R21HL175170?
R21HL175170 was awarded to Vitalant by National Heart Lung and Blood Institute (National Institutes of Health) on September 1, 2024.
How much is award R21HL175170 worth?
$262,500 has been obligated on R21HL175170.
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