RNAi therapy possibility for CMT 1A

[Guest guest]

(Note: Alnylam Pharmaceuticals, Inc has demonstrated the efficacy,

safety and delivery, in monkeys, of RNA interference (RNAi) therapy.

CMT 1A could be an ideal candidate for RNAi as we have seen through

much other research news.)

CAMBRIDGE, Mass.--(BUSINESS WIRE)--March 27, 2006--

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi

therapeutics company, announced today the first published

demonstration in primates that a systemically delivered RNAi

therapeutic can potently silence an endogenous disease-causing gene

in a clinically relevant manner. Alnylam and its collaborators at

Protiva Biotherapeutics, Inc., demonstrated silencing in primates of

the gene for apolipoprotein B (apoB), a protein involved in

cholesterol metabolism, with clinically significant efficacy as

demonstrated by reductions in levels of cholesterol and low-density

lipoproteins (LDL). This peer-reviewed research, published in the

world-leading scientific journal Nature, represents a major advance

because it suggests that an RNAi therapeutic can be effective when

delivered systemically using a dosage appropriate for application in

future human clinical studies.

In the published research, Alnylam scientists and collaborators

demonstrated potent silencing in primates of the gene for apoB, a

disease-causing protein which to date has not been amenable to

targeting with traditional small molecule, protein, or antibody

therapies. The achievement of this result by systemic administration

through the bloodstream demonstrates the broad potential of RNAi

therapeutics to target disease-causing genes, and significantly

expands the previously demonstrated opportunity for RNAi

therapeutics to treat human disease by direct administration to

sites of disease, such as with respiratory or ocular delivery.

" We believe that these findings both advance the field of RNAi and

expand the opportunity for RNAi therapeutics, as they represent a

launching pad to extend beyond our current clinical efforts with

direct RNAi therapeutics and address the broader potential of this

promising technology with systemic RNAi. These data give us

confidence that with further optimization of our systemic RNAi

platform we can move a systemic RNAi therapeutic candidate into

human clinical trials as early as the next 18-24 months, " said

Maraganore, Ph.D., President and Chief Executive Officer of Alnylam

Pharmaceuticals.

" Publication of these robust and well-controlled results in a

prestigious journal such as Nature is also further demonstration of

Alnylam's leadership position in the field of RNAi, our commitment to

scientific excellence and to applying this expertise for development

of innovative medicines. "

In the study published in Nature, Alnylam scientists and

collaborators showed that systemic delivery in non-human primates of

a chemically optimized small interfering RNA, or siRNA, can result

in silencing of the apoB messenger RNA (mRNA), leading to

significant reductions in blood levels of the apoB protein. These

effects were proven to occur through an RNAi-mediated mechanism, and

resulted in immediate, potent, and durable therapeutic efficacy. The

siRNAs were formulated with liposomes that enable delivery to liver

cells. The observed therapeutic effects included significant

reductions in serum levels of cholesterol and LDL, which together

represent the so-called " bad cholesterol " associated with

development of atherosclerosis and coronary artery disease.

Following administration of a single intravenous bolus dose at low

dosages from 1.0-2.5 mg/kg, these reductions were observed as early

as 24 hours after treatment and lasted for at least 11 days. A

single siRNA injection resulted in dose-dependent silencing of apoB

mRNA expression, with maximal silencing of over 90%. The silencing

of apoB was proven to occur through an RNAi-mediated mechanism of

action. In addition, plasma apoB levels were reduced by more than

75%, cholesterol levels by more than 60%, and LDL levels by more

than 80%. In the study of 18 animals, the treatment was well

tolerated with only transient liver enzyme elevation observed at the

highest dose. We believe the rapid and durable silencing of apoB

with RNAi is of clinical relevance, as it may represent a novel

strategy for reducing LDL-cholesterol in several clinical settings.

For more info on RNAi and ALNY go to http://www.alnylam.com/science-

technology/index.asp see also RNA articles at http://hnf-cure.org or

check the archives for past postings.