Synthetic compound may delay progression of scrapie, a prion disease that affects sheep and goats.

August 2, 2019

3 Min Read
NIAID JCI treatment ASO study.jpg
In these images of mouse brain infected with scrapie, the image on the left was treated with an inactive ASO and shows prion accumulation (brown). The image on the right was treated with an active ASO and shows little accumulation at a comparable timepoint.NIAID

Scientists using an experimental treatment have slowed the progression of scrapie, a degenerative central nervous disease of sheep and goats caused by prions, in laboratory mice and greatly extended the rodents' lives, according to a new report in JCI Insight.

According to an announcement from the National Institutes of Health/National Institute of Allergy & Infectious Diseases (NIAID), the scientists used antisense oligonucleotides (ASOs) — synthetic compounds that inhibit the formation of specific proteins — in the studies.

Prion diseases occur when normally harmless prion protein molecules become abnormal and gather in clusters and filaments in the body, including the brain, NIAID noted. The diseases are thought to be always fatal. Scrapie, which affects sheep and goats and can be adapted to rodents, is closely related to human prion diseases such as Creutzfeldt-Jakob disease, which is currently untreatable, as well as other transmissible spongiform encephalopathies.

In the studies, National Institutes of Health scientists and their colleagues injected ASOs into the spinal fluid of mice already infected with scrapie or that were challenged with scrapie proteins within weeks of the injection.

Ionis Pharmaceuticals specifically designed ASO1 and ASO2 to reduce the rodents' supply of normal prion protein, NIAID said. Rodent studies using different dosages of ASO1 and ASO2 were conducted at Rocky Mountain Laboratories (RML) in Hamilton, Mont., — part of NIAID — and at the Broad Institute of Cambridge, Mass.

RML scientists injected either ASO1 or ASO2 into mice 14 days prior to infecting them with scrapie, and then seven or 15 weeks after infection. Mice treated with ASO1 did not show clinical signs of disease for a median 250 days, or 82% longer than untreated mice (137 days), and they lived 81% longer than untreated mice (259 days versus 143 days), the announcement said. Mice treated with ASO2 did not show clinical signs of disease for a median 272 days, or 99% longer than untreated mice (137 days), and they lived 98% longer than untreated mice (283 days versus 143 days).

In the Broad Institute experiments, mice received either ASO1 or ASO2 two weeks before infection with scrapie and then seven weeks after infection. Both ASOs delayed rodent weight loss. Mice treated with ASO1 and ASO2 both lived longer than untreated mice, by 61% (274 days versus 170 days) and 76% (300 days versus 170 days), respectively, NIAID reported.

According to the announcement, the RML group also tested the ASOs against established prion disease, treating mice 17 weeks after they were infected with scrapie — near the onset of clinical signs. Mice treated with ASO1 did not show signs of clinical disease for a median 189 days, or 33% longer than untreated mice (142 days). They also showed slower disease progression and lived 55% longer than untreated mice (244 days versus 157 days). ASO2 had no beneficial effect.

The researchers plan to expand their scrapie ASO studies to prion diseases, while other researchers have seen promising initial results in humans with ASOs directed against Alzheimer's disease, amyotrophic lateral sclerosis (Lou Gehrig's disease) and Huntington's disease.

Source: NIAID, which is solely responsible for the information provided and is wholly owned by the source. Informa Business Media and all its subsidiaries are not responsible for any of the content contained in this information asset.

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