Another drug

A board to discuss future MS therapies in early stage (Phase I or II) trials.

Another drug

Postby bromley » Fri Nov 10, 2006 12:46 pm

Not really sure what this drug does, but mentions MS.

AVI BioPharma Announces Positive Clinical Trial Results Delivering NEUGENE Antisense Drugs to the Central Nervous System 10 November 2006

AVI BioPharma, Inc. today announced human clinical trial results showing that three distinct NEUGENE® antisense drugs entered the cerebral spinal fluid (CSF) of healthy adult male volunteers following a single 100 mg dose via intravenous (IV) or subcutaneous (subq) injections. The three drugs used were AVI-4020, targeting West Nile virus (WNV); AVI-4065, targeting Hepatitis C virus (HCV); and AVI-4126, targeting the c-myc oncogene.

"We believe the presence and persistence of each of the three NEUGENE drugs in the CSF after a single administration suggest potentially unique therapeutic applications for this class of antisense drugs," said Dr. Peter O'Hanley, senior vice president of clinical development and regulatory affairs at AVI BioPharma. "It might be possible to treat central nervous system diseases like Alzheimer's disease, brain tumors and multiple sclerosis."

Among the three studies, a total of 29 adult male volunteers had evaluable drug levels in the CSF after a 100 mg administration of each NEUGENE drug. Eleven volunteers received AVI-4020 via IV, 12 received AVI-4065 via subq and six received AVI-4126 via IV. Four representative CSF samples were obtained from the volunteer cohort at each six-, 12- and 18-hour time point after a single dose administration (not all volunteers had samples taken at each time period).

For AVI-4020 treatment, all volunteers had detectable drug in the CSF at each of the three time points and at approximately the same levels, averaging 20.5 ng/ml CSF. The presence of AVI-4020 in the CSF was expected, based upon an earlier Phase I study in patients with suspected WNV infection.

For AVI-4065 treatment, all volunteers had detectable drug in the CSF at each of the three time points and at approximately the same level, averaging 33.3 ng/ml CSF. This amount of drug in the CSF was about 60 percent higher than drug levels found in AVI-4020-treated volunteers and is believed to be related to the differences between the nucleotide motifs.

In the case of AVI-4126 treatment, there was no detectable drug in the CSF at six hours among the four volunteers from whom samples were taken at that time point. Two of four volunteers had detectable drug in the CSF at 12 hours, and three of four volunteers had detectable drug in the CSF at 18 hours. Among AVI-4126 detectable CSF samples, there were approximately equivalent amounts of drug detected at the latter two time points, averaging 13.2 ng/ml CSF. AVI scientists believe that the variability of CSF penetration for this drug also relates to the intrinsic differences in the nucleotide motif versus the other test drugs.

AVI believes its NEUGENE antisense rapid response therapeutics will play a significant role in the future of antiviral therapeutics, including in treating emerging infectious diseases that threaten public health, or in addressing bioterrorism.

AVI has the manufacturing capacity to produce clinical-grade NEUGENE antiviral therapeutics, targeting viral pathogens, for a limited number of patients within days. NEUGENES are synthetic compounds that mirror a critical portion of a disease-causing organism's genetic code and bind to specific portions of the target genetic sequence. Like a key in a lock, NEUGENE antisense compounds are designed to match up precisely with a specific gene or viral sequence, blocking its function.

Source: AVI BioPharma, Inc.
User avatar
bromley
Family Elder
 
Posts: 1887
Joined: Fri Sep 10, 2004 3:00 pm

Advertisement

Postby sh8un » Fri Nov 10, 2006 12:57 pm

uhhh...do I really want ANTI SENSE drugs entering my CSF??? :lol: Possibly...all the drugs that make sense are not really helping. Lets try some antisense ones.
NN
sh8un
Family Elder
 
Posts: 303
Joined: Wed May 03, 2006 3:00 pm
Location: Calgary, AB, Canada

Postby dignan » Fri Nov 10, 2006 4:12 pm

Interesting. AVI is in the pre-clinical section of the pipeline already for their exon-skipping yada yada yada that I can't quite figure out. I'm not going to add anything else based on this article because they mention 3 substances and then mention MS later, but not in connection with one particular drug...unless somebody knows which one they're testing for MS...
User avatar
dignan
Family Elder
 
Posts: 1608
Joined: Wed Aug 11, 2004 3:00 pm

Postby Lyon » Fri Nov 10, 2006 4:15 pm

oo
Last edited by Lyon on Sat May 07, 2011 5:38 pm, edited 1 time in total.
Lyon
Family Elder
 
Posts: 6063
Joined: Wed May 03, 2006 3:00 pm

Re: Another drug - making sense of antisense

Postby NHE » Sat Nov 11, 2006 11:25 pm

This paragraph appears to be key to understanding their experimental therapies.
AVI has the manufacturing capacity to produce clinical-grade NEUGENE antiviral therapeutics, targeting viral pathogens, for a limited number of patients within days. NEUGENES are synthetic compounds that mirror a critical portion of a disease-causing organism's genetic code and bind to specific portions of the target genetic sequence. Like a key in a lock, NEUGENE antisense compounds are designed to match up precisely with a specific gene or viral sequence, blocking its function.

To the best of my recollection, in a nutshell, DNA is composed of two strands, a sense strand which is transcribed into RNA to make protein and an antisense strand which runs in the opposite direction. For example, if a sequence of DNA for a gene from the sense strand reads...

CTGAATTTACGGAATCAG then the antisense strand would read
GACTTAAATGCCTTAGTC

...since the base adenine, A, binds to the base thymine, T, and the base cytosine, C, binds to the base guanine, G. In RNA the base T is replaced by uracil, U. It's a fairly common experimental procedure to try to knock out the function of a gene by using antisense RNA. The antisense RNA will have the opposite sequence of RNA which is used to synthesize proteins at the ribosome and will bind to RNA preventing its translation into protein. By using antisense RNA my best guess is that they are trying to knock out the function of a specific gene. If this type of therapy is already in clinical trial, then it suggests that they've had success using animal models knocking out specific genes. I would be very interested in knowing which specific genes they were targetting for MS!

NHE
User avatar
NHE
Volunteer Moderator
 
Posts: 3247
Joined: Sat Nov 20, 2004 4:00 pm

Postby dignan » Sun Nov 12, 2006 11:57 am

The most advanced antisense treatment for MS is ATL1102. Antisense Therapeutics started ATL1102 in a phase II trial in late 2004. Since it's target is the same as tysabri's, the trial was suspended for a while, but it's underway again...


http://www.thisisms.com/ftopict-717-atl1102.html

http://www.thisisms.com/ftopict-2631-atl1102.html
User avatar
dignan
Family Elder
 
Posts: 1608
Joined: Wed Aug 11, 2004 3:00 pm


Return to Drug Pipeline

 


  • Related topics
    Replies
    Views
    Last post

Who is online

Users browsing this forum: No registered users