Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Biotech Valuation -- Ignore unavailable to you. Want to Upgrade?

To: NeuroInvestment who wrote (8265)	5/6/2003 7:56:17 AM
From: John McCarthy	Read Replies (2) \| Respond to of 52153

This may or may not interest you ... but thought I'd pass it on .... (its more or less hot off the press) 1204. Inhibition of Neurotoxic Aggregate Formation and Extension of Neuronal Cell Survival in Huntington’s Disease by Short, End- Modified, Single-Stranded DNA Oligonucleotides Hetal Parekh-Olmedo,1 Yiling Hu,1 Eric B. Kmiec.1 1Department of Biological Sciences, University of Delaware, Newark, DE, United States. The development of protein aggregates composed of the Huntington protein (Htt) and other cellular factors, such as chaperones and heat shock proteins, capases, and transcription factors, eventually lead to neurotoxicity and cell death. Therapeutic approaches are now focused on agents that can inhibit either the nucleation or elongation phase of aggregate development. We have discovered short synthetic oligonucleotides, containing certain types of modified termini conferring nuclease resistance, to inhibit aggregate formation and, surprisingly, extend neuronal cell life by at least 40%. Neuronal cells were induced to produce aggregates after being transfected with oligonucleotides varying in length from 53 bases to 6 bases, with phosphorothioate linkages at the termini. These molecules reduced the number of cells bearing Htt aggregates by > 60% routinely. Oligomers of identical length, but containing 2’-Omethyl RNA or locked nucleic acid modifications, were ineffective in inhibiting aggregate formation and neurotoxicity. These oligonucleotides can be of random sequence, but must be singlestranded; double-stranded PCR products and double-stranded hairpins do not support inhibition. In a neuronal cell line in which the induction of aggregate formation (through Htt expression) leads to cell death, short single-stranded oligomers were found not only to prevent aggregate formation, but also to promote cell survival and, possibly, expansion and growth. Taken together, we have developed a gene therapy approach to Huntington’s Disease using a pharmacologically-useable product, which should reduce the complications associated with viral-based approaches. Beyond the importance of the inhibition of aggregate formation, the unprecedented novelty of this treatment is that it increases the survival of neurons bearing reduced levels of neurotoxic inclusion bodies. messages.yahoo.com John McCarthy