from NYTimes today:

July 27, 2007

Patient in Experimental Gene Therapy Study Dies, F.D.A. Says

By DENISE GRADY and ANDREW POLLACK
A patient has died in a study of an experimental gene therapy, the Food and Drug Administration reported yesterday. The agency said it was investigating the death to determine whether the treatment was to blame.
The case could be another setback for gene therapy, a field with a troubled history and numerous treatment failures, including the death of a teenager in 1999 in an experiment.
The new therapy being tested, made by Targeted Genetics of Seattle, is a virus-based product injected directly in the joints in hope of relieving active inflammatory arthritis. That chronic condition can affect multiple joints and organs, and it is quite different from the wear-and-tear arthritis that commonly occurs with aging.
The patient became ill soon after receiving a second injection, the drug agency said. The date is not exactly clear, but the illness was recognized as a “serious adverse event” last Friday, and the agency immediately suspended the study. That means no more injections can be given. The patient died on Tuesday.
Targeted Genetics and the drug agency said they would not describe the patient’s symptoms or the manner of death until the investigation had been completed. The company and the agency emphasized that it was not known whether the treatment had a role or the death was a coincidence. The agency said the timing was cause for concern.
H. Stewart Parker, chief executive of Targeted Genetics, said, “The patient was dosed one dose and had no issues and came back several months later and coincident with the dosing had an S.A.E.”
S.A.E. is an abbreviation for serious adverse event.
Ms. Parker said the company had used the same type of virus to carry various genes into more than 500 patients and had not seen similar problems. “These patients are all on several different medications,” she said. “They certainly have disease characteristics.”
The drug agency said it was reviewing all other studies using the same virus, which is called an adeno-associated virus, though it had not heard of similar problems.
Dr. Theodore Friedmann, a professor of pediatrics and head of the gene therapy program at the University of California, San Diego, said the A.A.V. system used in the experiment was widely regarded as safe.
But, Dr. Friedmann added, “We’ll probably come to learn it does some harmful things in some settings.”



__._,_.___

Gene therapy using adeno-associated virus linked to liver cancer in mice

By Caroline Arbanas

July 26, 2007 -- Researchers at Washington University School of Medicine in St. Louis have found further evidence linking a method used to deliver gene therapy in humans with the development of liver tumors in mice.
The new research, published in the July 27 journal Science, suggests that ferrying a corrective gene into mice using a disabled virus - an adeno-associated virus (AAV) - inadvertently inserts mutations into the mouse DNA that initiate tumor growth. The same delivery method is also used in some gene therapy clinical trials in humans, but as of yet no studies have found an association between the AAV vector and cancer in patients.
Still, the Washington University scientists, led by Mark Sands, Ph.D., associate professor of medicine and genetics, say the data in the team's latest study raise important safety concerns about the use of AAV vectors in patients receiving experimental gene therapy. "While the findings do not eliminate AAV as a potential therapeutic tool, more research is needed to determine the possible long-term toxicity of the AAV vector in humans," Sands cautions.
more at:
http://mednews.wustl.edu/news/page/normal/9733.html

Acknowledging these, with confidence and hope that a connection to your gene therapy is not there.

We are watching with such anticipation, the virus seems to be the concern but it's so early to know.

During the next several months, I anxiously await a positive change in these participants.

But another part of me, is still ****** off that we shouldn't have to be in such a hurry to get gene therapy when a treatment that works safely (and is incorrectly described as not being safe repeatedly -NO SIDE EFFECTS in 3 yrs) could already be on the market as we await this cutting edge treatment.

We're holding our breath again to see what this means, for those using the virus for delivery.

Anything you can tell us or want to unload some feelings here Carolyn or Dottie?


Paula

seems to me that too many judgments are being made in the media before the cause of death has even been determined.

even though it might be a mistake to be withholding gdnf treatment, I do not think it is rushing things to be in stage two clinical trials for AAV gene therapy - we need to be fighting all diseases on all fronts.

medical research is a risky business; if well and properly informed, patients should be allowed to assume the risk involved in ground-breaking clinical trials. There's really no other way to move the science forward.

I remember a few yrs back the drug Eldepryl (Selegline) was taken off the market for a while due to some deaths. Yet only a short time before that it was touted as possibly neuroprotective, it came back into favour and still is prescribed as far as I know
Then there's Tasmar, it's been known to cause liver failure and death so (it may have changed) but monthly liver function tests were/are mandatory.
These drugs are still given to parkinsonians.
I guess my point is who do we listen to and how much do we as patients want to risk the catastrophic events that can happen when we take a tablet, or undergo experimental procedures?
It's a really personal decision we do or don't take and open to debate.
In a way I'd like the general media to keep out of it but I guess they do there bit as a source of information to the public.
Lee

Dear Members,

About two weeks ago, I helped with my churches' Bible School. One young girl was very artistic, but had been diagnosed with reumatoid arthritis since birth. She was very short and obviously retaining water, as she was very heavy and her face was swollen so her eyes were difficult to see for all the fluid retained in her face. Her name was Arrian and she was to go to Washington to have stem cell surgery from stem cells obtained from her bone marrow.

A week later my husband and I attended a carnival to raise funds for her surgery. Their were games for the kids and projects for auction made at the Bible School. My husband and I bid on a stained glass piece that Arrian had made. Arrian was a very artistic. She was very careful to choose her colors and stayed carefully in the lines.

Arrian was to be the first child to receive this procedure. I will see her Aunt at church on Sunday and ask if Arrian was the patient who had the surgery. I know she had a lot of pain and she frequently complained to me of tremors.
The surgery was her only hope of leading a normal life.

I have asked the Right to Life group associated with my church and received the following responce to give to those who deem that the option of discarding unused embryo's into the trash was a waste when they could be used to help others. Please consider it carefully and give it thought before replying. Any sarcastic responces will be ignored.

Dear Vicky,

First of all, my prayers go out to you as you fight two battles -
Parkinson's and attacks on your faith. I pray that God gives you the
strength to face these challenges and maintain your strong faith through
each of them.

The arguments that you are hearing are very typical, even among
Christians. The basis of that opinion is misleading though. Most
people believe there are only two options for those embryos: destroy
them in a trash can or destroy them in a scientist's lab. The
assumption continues that if they will be destroyed anyway, why not get
something good from their destruction.

The first correction to that thinking is that there are actually five
options for those embryos, not only two options. They are:
1) throw them in the trash
2) donate them to scientists for research
3) keep them frozen indefinitely
4) transfer them to the mother for the chance they will implant and
continue living
5) place them for embryo adoption so infertile couples can have the
chance for children

Of these five, there are certainly issues with each and none of them are
"easy" choices for couples. Yet, of these five choices the first two
are clearly wrong because the intent is to destroy them. The third
choice is really not much better because the destruction of those
embryos is probably just delayed. The last two, however, are options
that protect the lives of the embryos and even gives infertile couples
the opportunity to give birth to a child.

You made an interesting comment that has value in this debate.
Infertility treatments are designed to bring new lives into this world.
The "success" of IVF has produced many more embryos than are needed by
those infertile couples, but that success should be used to benefit
others who want children. It seems rather illogical to destroy those
embryos rather than use them for their intended purpose.

The truth is that you need to do some educating. Embryos are young
lives that should be allowed to continue their existence. The intent of
infertility treatments is to bring children into the world. There is no
other reason to go to an infertility specialist and no other goal other
than the birth of children. For some people to step in and say that these
embryos should now be used for some other purpose is contrary to the
entire process and intent. If your friends are wishing that science
would find a cure or treatment for Parkinson's through embryonic stem
cell research, then they should look at the work being done to establish
embryonic stem cells without destroying human lives. Such research is
currently being done at Harvard, MIT, University of Minnesota, and
others. In those cases, the stem cells are intended for treatments and
are formed in ways that are more ethically acceptable. I would ask your
friends if they see the benefit of splitting this technology so the
infertility clinics remain focused on bringing babies into the world and
researchers are focused on finding cures for diseases. This approach
protects the value of human life, but does not limit the potential for
success with embryonic stem cell research. If your friends cannot see
the logic in this argument, then you probably are not going to get
through to them. Some people are so hardened in their opinions that
even facts and logic are not going too change their minds.

You also raised another interesting point. Should science be limited or
censored in any way? Yes, of course it should be and it is in virtually
all countries in the world. Science without limits was practiced in
Germany in the early and mid 20th century and the world has condemned
them soundly for it. Science, by its nature, is a field of study and
discovery. We often think that discovery should be free and unlimited
because it will benefit mankind in the end. The truth is that
scientists must be limited because free discovery is not usually
beneficial for mankind. Currently in the United States, we have
government agencies and scientific organizations that oversee the fields
of science. This is appropriate for two reasons: (1) scientists are
not, and should not be, capable of self-limitations. It is not fair to
the field of scientists to expect each one of them to hold to a
consistent ethic and universal standards, if no such standards have been
established. (2) such limitations are often based on a combination of
religious beliefs, ethical standards, and general public opinion. Our
government is specifically designed to represent the general public and
reflect the opinions and standards that are felt by the majority of its
citizens. Therefore, the government is rightly responsible for setting
those standards and enforcing them. Quite honestly, my perception is
that the government has accomplished this role very effectively. We
have continued technological advancements, and for the most part, we
aren't creating a bunch of research that is unacceptable to the general
populace. In summary, the argument that scientists should be free to
pursue their research is simply not thinking this through very well and
coming to a conclusion that is based on shallow emotionalism rather than
reasoned logic.

In the end, Vicky, remember that your role as a Christian is to live
your life as a shining example of faith (Matthew 5) and to always be
prepared to give the reason for the hope that you have for your
salvation (1 Peter 3). You are struggling with ways to win this debate
with your friends, but the greater challenge is to use this debate as a
way to reflect your faith and the truths of God's Word. The arguments
they are giving you are all based on emotionalism and humanism. Your
responses should always be based on Biblical principles and spoken in
love (Ephesians 4). In your responses I would encourage you to provide
some of the information and facts that I listed above. Let your friends
know that you are informed on this topic and not making blind
assumptions. Your strongest argument, however, is found in God's Word.
We know that those embryos are human lives (Psalm 51), we know that we
do not have the right to intentionally kill human beings (Exodus 20) and
we know that God holds us accountable for the lives of our fellow human
beings (Genesis 9). At the same time, we are responsible to preserve
and protect human life and treat our neighbor in love (Luke 10).
Putting these Biblical truths together, it is easy to conclude that we
should support and encourage advancements that are able to treat people
with illnesses or diseases. Yet, we cannot justify procedures that
intentionally destroy human lives for the perceived hope that we might
find a cure to save others. It simply is not consistent with God's
Word.

Lord's blessings on your efforts, Vicky.

Paul Snamiska
Program Administrator
Christian Life Resources

I have asked for the Christian Life Resources to state my beliefs in a non-judgental way as many on this site find me too sure of the rightness of my beliefs. That is what Faith is. Faith is not an emotion. It is the sureness that God requires nothing from us to save ourselves, nor does he believe we are able to life our lives without breaking the ten commandments. He gave his only son for our sake, so by his grace we can be saved. We cannot save ourselves or pray our way into heaven. We can only read his word, attend his church to receive his word and the lord's supper and try to do his will to the last.

If you are an athiest, please ignore this post. But if you consider yourself a Christian please give the Program Admistrator of Christian Life Resources serious thought. I believe that reverence for life was one of Jesus top priorties when he was on this earth, as he showed mercy on even those whom cursed and crucified them on the cross.

Sincerely,
Vicky Lynn

"On July 24, 2007 the U.S. Food and Drug Administration (FDA) was informed by Targeted Genetics Corporation of Seattle about the death of a patient who received an investigational gene therapy product in a clinical trial for the treatment of active inflammatory arthritis.

FDA's condolences go to the patient's family.

FDA is providing this preliminary information in recognition of the public's interest in these types of new therapies.

Targeted Genetics notified FDA earlier that a patient in its trial experienced a serious adverse event. Even though the cause of the illness wasn't known, and is still uncertain, the agency immediately placed the trial on clinical hold--meaning no further product can be administered and no new patients can be enrolled.

The product that was being studied uses a particle called a vector that is designed to deliver treatment genes to target cells. The vector used is a recombinant adeno-associated virus (AAV) derived vector and delivers the gene for Tumor-Necrosis Factor -Receptor, with the intent to inhibit a key mediator of inflammation. In the study, the gene therapy was administered into the joint affected by the disease to reduce inflammation and disease in patients with active inflammatory arthritis.

More than 100 subjects have been enrolled in the trial, according to the company, without known similar serious events. However, the patient's illness was related in time to the receipt of a second injection of the product. Upon being alerted to the adverse event, FDA immediately began its investigation to determine whether the illness was related to the treatment. The investigation into the cause of the patient's illness and subsequent death is intensive and ongoing.

Targeted Genetics is cooperating with FDA's investigation and has agreed to provide the agency with ongoing results from various tests and all other information it is compiling that may help determine the cause of this patient's death. FDA is also coordinating with the National Institutes of Health in an effort to acquire a better understanding of the potential scientific and safety implications of this event. These matters will be discussed at the September meeting of the NIH Recombinant DNA Advisory Committee.

FDA is not aware of similar adverse events occurring in other gene therapy trials either with this specific product or with those that use other genes in AAV vectors. However, as a precaution, the agency is further reviewing all ongoing trials involving any use of AAV.

FDA recognizes the contributions of participants in clinical trials and places a high priority on potential safety issues – volunteers play a critical role in making treatments available that have the potential to help many other patients who need new treatments for serious diseases.
The agency is continuing to obtain and assess additional information to help determine, if possible, the cause of the event, and any potential implications and will take additional steps and provide updates as warranted".

Neil.

p.s. Vicky, shouldn't your post have been labelled "Off Topic".

Thanks, Neil for bringing us back on-topic!

Much appreciated.

http://ir.targen.com/phoenix.zhtml?c...343&highlight=

"SEATTLE, WA, Jul 26, 2007 (MARKET WIRE via COMTEX News Network) -- Targeted Genetics Corporation (NASDAQ: TGEN) provided an update today on its development program of tgAAC94, an investigational therapy for the treatment of inflammatory arthritis. This Phase I/II study is designed to assess the safety and potential efficacy of different doses of tgAAC94 administered directly into affected joints of subjects with inflammatory arthritis. As we previously announced on July 24, the Company and the United States Food and Drug Administration (FDA) stopped the trial as a precautionary measure after the occurrence of a Serious Adverse Event (SAE) in one subject. The individual who experienced this SAE has subsequently died.

"We are deeply saddened by the death of an individual enrolled in our clinical trial. The welfare of the trial participants is always our foremost consideration and concern," said H. Stewart Parker, president and chief executive officer of Targeted Genetics.

Parker adds, "The clinical course that this individual experienced has, to our knowledge, never been seen as a consequence of exposure to adeno-associated viral (AAV) vectors or naturally occurring AAV. We continue to work closely and diligently with the FDA and the study's independent Data Safety Monitoring Board to determine the cause of the SAE as quickly as possible."

Subjects already enrolled in the study will continue to be followed and monitored. Since the trial began in October 2005, 127 subjects have received an initial dose of active drug or placebo, 74 subjects out of the total 127 have received a second dose of active drug, and of those 74 subjects, 55 have received two doses of active drug.

tgAAC94 is an investigational therapy utilizing an adeno-associated virus (AAV) vector to deliver the gene encoding a soluble form of the receptor for TNF-alpha (TNFR: Fc). The TNFR:Fc protein is an inhibitor of tumor necrosis factor-alpha (TNF-alpha), a key mediator of inflammation. In March 2006, the Company received approval from the FDA to amend its protocol for the tgAAC94 clinical trial to include a higher dose group and increase the number of patients. 127 adults have been randomized into three dose levels to receive a single intra-articular injection of either tgAAC94 or placebo into the knee, ankle, wrist, metacarpophalangeal or elbow, followed by an open-label injection of tgAAC94 after 12 to 30 weeks, depending on when arthritis symptoms in the target joint meet criteria for re-injection".

Neil.

Paula - thank you for your concern.

I had my one month post-op visit and don't go back for another two months. I am still confident that I made the right decision for myself at the
right time.

Since we know nothing about this individual I prefer to wait untill we at least know the cause of death before jumping to conclusions. As Carey states so well "medical research is a risky business"

My condolences to the family.


Dottie