I attended another AVGN stockholders meeting today and feel much better for it. The news about (1) an epidemiological study linking AAV with male infertility and (2) AAV vector’s showing up in a patient’s semen had been getting me kinda down. Here’s what I learned that cheered me up.
1) What showed up in semen was just DNA fragments and not necessarily entire vectors. The analysis was done using PCR technology, which is much more sensitive. The quantities were so small they never would have detected them otherwise.
2) The patient in whom this DNA fragments were detected was 64 years old. Being not very active, sexually, lots of time passes between seminal emissions (I’m trying to be polite, here), so any DNA fragments that may be floating around have time to accumulate and produce a detectable concentration. Monahan doesn’t expect younger patients will show detectable levels of DNA fragments in their semen.
3) No DNA fragments were detected in sperm. This is important. Monahan said scientists have tried to get vectors to transmit DNA to sperm cells and have never been successful, so he thinks it very unlikely that AAV vectors would ever deposit any DNA into sperm.
4) No DNA fragments had ever been encountered in semen during the canine trials.
5) DNA fragments were also detected in this 64-year-old’s serum and saliva (I guess that isn’t particularly positive or negative, but Monahan seemed surprised by that the DNA fragments showed up in saliva).
6) Monahan had serious questions about the epidemiological study linking AAV to male infertility. In any event, it would seem that once you strip out DNA from the AAV virus and prevent the virus from replicating in the body, the chances of causing any infertility problems must be very remote. And what the heck, if you are so defective as to need gene therapy, infertility may be a blessing (not very PC, am I?).
The biggest event on the near horizon will be a special RAC Meeting on 12-6-2001. It has been two years since the RAC has held a hearing on the issue of transmission of DNA into germ cells. Obviously, everyone is against that happening, but the issue seems to be what kind of testing must be performed and evidence collected to prove a negative – that no germ-cell line transmission is occurring. AVGN said many other gene therapy companies will be attending this RAC meeting. The issue isn’t by any means limited to AAV.
If AVGN gets a green light from the RAC on 12-6-2001, they could get started with the next patient in their Coagulin B trial in just a couple weeks. But that’s the best case scenario.
With AVGN’s stock price so low, I’m tempted to load up, but I don’t like the uncertainty about what the RAC will do. So I’ll probably stick tight until I receive news from that meeting.
Other news from the meeting:
One of the dog’s treated with the Factor IX vector four years ago is still alive and well, and still producing Factor IX. In humans, Monahan’s expectation is that patient’s will get a booster treatment every 2-3 years. He says that after one year the antibodies have pretty much cleared out, so no immune response would be expected during a retreatments spaced 2-3 years apart.
Monahan was very proud of the results from the completed Phase I trial using muscular injection. This is the first time anyone has demonstrated long-term gene expression following single treatment of DNA. But the study showed that one would need to use much larger doses (if administered intramuscularly) to achieve the desired clinical benefit. On the other hand, he produced graphs showing that humans behave much better than mice and dogs in terms of ratio of (a) vector quantity to (b) Factor IX quantity produced following treatment. He said that this is what one should expect, inasmuch as AAV is a human virus, and not a murine or canine virus.
AVGN hopes fairly soon (I don’t recall how many weeks) to file for an IND for a Parkinson’s therapy. In order to produce Dopamine, PD patients are treated with L-Dopa, which requires an AADC enzyme in order to be converted into Dopamine. The problem is that PD patients gradually lose the ability to produce AADC, because the cells that express it eventually die off. AVGN combines the AADC gene with a promoter into an AAV vector, so that they can trigger other cells in the brain to produce the necessary AADC. AVGN had excellent results in a primate study.
That’s about it.
Cheers,
Marc |
