Tuesday, January 26, 2010
SPC3649 ( LNA- locked nucleic acid) - a new hope for hepatitis C.....
Friday, May 30, 2014
Isis Pharmaceuticals starts Phase 1 clinical study of ISIS-PKKRx to treat patients with HAE
Friday, November 20, 2009
Positive results from mipomersen- a new hope for FH sufferers...
Familial hypercholesterolemia (also spelled familial hypercholesterolaemia) is a genetic disorder characterized by high cholesterol levels, specifically very high low-density lipoprotein (LDL, "bad cholesterol") levels, in the blood and early cardiovascular disease. Many patients have mutations in the LDLR gene that encodes the LDL receptor protein, which normally removes LDL from the circulation, or apolipoprotein B (ApoB), which is the part of LDL that binds with the receptor; mutations in other genes are rare. Patients who have one abnormal copy (are heterozygous) of the LDLR gene may have premature cardiovascular disease at the age of 30 to 40. Having two abnormal copies (being homozygous) may cause severe cardiovascular disease in childhood. Heterozygous FH is a common genetic disorder, occurring in 1:500 people in most countries; homozygous FH is much rarer, occurring in 1 in a million births.
Heterozygous (FH) is normally treated with statins, bile acid sequestrants or other hypolipidemic agents that lower cholesterol levels. New cases are generally offered genetic counseling. Homozygous FH often does not respond to medical therapy and may require other treatments, including LDL apheresis (removal of LDL in a method similar to dialysis) and occasionally liver transplantation.
Recently, Genzyme Corp. and Isis Pharmaceuticals Inc have come up with some intresting results from the drug mipomersen [mipomersen - is an antisense oligonucleotide, with phosphorothioate linkage at 5'- postion and 2'-O-methoxymethyl moety] ( phase 3). As per the claim by the companies, the study met its primary endpoint in an intent-to-treat analysis, with a 25 percent reduction in LDL-cholesterol after 26 weeks of treatment, vs. 3 percent for placebo (p<0.001)>.
The trial met all of its secondary and tertiary endpoints, suggesting that mipomersen may offer potential benefits to patients beyond LDL-C reduction. Patients treated with mipomersen experienced a 27 percent reduction in apolipoprotein B vs. 3 percent for placebo; a 21 percent reduction in total cholesterol vs. 2 percent for placebo; and a 25 percent reduction in non-HDL cholesterol vs. 3 percent for placebo (all p<0.001).>Mipomersen patients’ HDL-C levels increased 15 percent (p=0.035 vs. placebo), which combined with the LDL-C reductions observed, resulted in improved LDL/HDL ratios, a ratio considered an important measure of cardiovascular risk. Mipomersen patients’ LDL/HDL ratios decreased by 34% (p<0.001>Mipomersen a representative of Isis’ leadership in the field of RNA targeted therapeutics will bring a sigh of relief to the sufferers of FH, in the days to come.
I had an opportunity to work with ISIS (as contract R & D, Innovasynth Technologies Limited, Khopoli) and really excited to see the results..
Ref : http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-newsArticle&ID=1356364&highlight=
Sunday, January 25, 2009
Diverse use of Nucleic acids.....
There are many oligonucleotides with modified chemical backbones, like peptide nucleic acids (PNAs), locked nucleic acids (LNAs), methylphosphonates, phosphoramidates and thiophosphoramidates. Each of these types of oligonucleotides has reported advantages and disadvantages. For example, peptide nucleic acids (PNAs) display good nuclease resistance and binding strength, but have reduced cellular uptake in test cultures; phosphorothioates display good nuclease resistance and solubility, but are typically synthesized as P-chiral mixtures and display several sequence- non-specific biological effects; methylphosphonates display good nuclease resistance and cellular uptake, but are also typically synthesized as P-chiral mixtures and have reduced duplex stability.
The N3'-P5'phosphoramidate internucleoside linkages are reported to display favorable binding properties, nuclease resistance, and solubility (I did work for quite some time in this field and I had opportunity to interact with Dr. Sergei Gryaznov and group). Though this field is getting wider and wider with many companies trying with some innovative ideas, the real concern in this field is that the polyanionic nature of oligonucleotides reduces the ability of the compound to cross lipid membranes, limiting the efficiency of cellular uptake.But thanks to many other groups they are trying to concentrating on this issue and hope there will be may drugs in the days to come. There are many drugs already in the market by ISIS and Geron corporation has many patents to its credit in the many patents for its novel work (Dr.Sergei, Dr.Cristzina Pongracz and many others have lot of work in this field) N3'-P5'phosphoramidate internucleoside linkages. Though there were a few players in this field of nucleic acids(5-6 years' back), now a days when ever I read any medicinal chemistry news, I do find lot many companies contributing to this field of nucleic acids. Hope there will be many drugs from this field with reduced side effects....
Saturday, August 1, 2009
New journal devoted to gene therapy...
URL : http://www.genetherapyreview.com/index.php
Blog : http://www.genetherapyreview.com/gene-therapy-blog.html
Saturday, August 18, 2018
FDA Advisory Committee Votes in Favor of Waylivra (volanesorsen) for Treatment of Familial Chylomicronemia Syndrome
3’—A*—G*—mC*—T*—T*—dmC—dT—dT—dG—dT—dmC—dmC—dA—dG—dmC—T*—T*—T*—A*—T*—5’
*
= 2’-O-(2-methoxyethyl)m
= 5-methyld
= 2’-deoxy“We thank the committee members for their time and their comments today. The Committee’s majority vote in favor of approval is an important positive step to bring Waylivra to people with FCS who have no adequate treatment options,” said Paula Soteropoulos, chief executive officer of Akcea Therapeutics. “We look forward to working with the FDA to complete the final stages of regulatory review for Waylivra. We are committed to the FCS community and will continue to focus on bringing Waylivra, potentially the first and only treatment, to people living with this serious and potentially fatal disease.”
“Given the severity of FCS and the burden it places on patients, the need for a therapy is critical. The progress in development of a potential first-ever treatment is very encouraging. The planned efforts in monitoring and education are designed to achieve the highest levels of patient adherence, compliance and safety,” said Dr. Seth Baum, president, American Society for Preventive Cardiology. “The medical community is eager to have a medicine to treat our patients with FCS.”
“People with FCS have severely elevated triglycerides, which lead to multiple severe daily and chronic symptoms, such as abdominal pain and increased risk for pancreatitis, which can be fatal. Waylivra is the first drug to demonstrate substantial triglyceride lowering in clinical trials in people with FCS,” said Brett P. Monia, chief operating officer at Ionis. “Waylivra illustrates how our antisense technology can create targeted drugs for people living with severe diseases who currently have no available therapeutic options.”
Ref : http://ir.akceatx.com/news-releases/news-release-details/fda-advisory-committee-votes-favor-waylivra-treatment-familial
Friday, June 15, 2012
Ebola, Marburg Virus Treatments Safe in Phase 1 Studies
"We are very encouraged that these two drugs, which use our advanced PMOplus chemistry, have demonstrated a favorable safety profile through five cohorts in our dose-escalation studies,”says Chris Garabedian, president and chief executive officer of AVI BioPharma...
Monday, April 25, 2011
Tuesday, November 16, 2010
Regulus present advancements in microRNA platform at Oligonucleotide Therapeutics Society meeting
Regulus present advancements in microRNA platform at Oligonucleotide Therapeutics Society meeting
Thursday, September 21, 2017
New drug shows promising results for treating spinal muscular atrophy
Sunday, November 1, 2009
Geron plans to advance clinical program for spinal cord injury
As I had an opportunity to talk and work (contract research) with Geron [known for its first-in-class biopharmaceuticals (especially "antisense drugs" from oligonucleotides) for the treatment of cancer and chronic degenerative diseases] company, I know its credentials and am really excited to see some interesting out come from their advance clinical program. All the best....
Ref : http://www.geron.com/media/pressview.aspx?id=1195