: Neurology. 2009 Oct 14. [Epub ahead of print] Links
Safety and tolerability of putaminal AADC gene therapy for Parkinson disease.Christine CW, Starr PA, Larson PS, Eberling JL, Jagust WJ, Hawkins RA, Vanbrocklin HF, Wright JF, Bankiewicz KS, Aminoff MJ.

BACKGROUND: In Parkinson disease (PD), the benefit of levodopa therapy becomes less marked over time, perhaps because degeneration of nigrostrial neurons causes progressive loss of aromatic L-amino acid decarboxylase (AADC), the enzyme that converts levodopa into dopamine. In a primate model of PD, intrastriatal infusion of an adeno-associated viral type 2 vector containing the human AADC gene (AAV-hAADC) results in robust response to low-dose levodopa without the side effects associated with higher doses. These data prompted a clinical trial. METHODS: Patients with moderately advanced PD received bilateral intraputaminal infusion of AAV-hAADC vector. Low-dose and high-dose cohorts (5 patients in each) were studied using standardized clinical rating scales at baseline and 6 months. PET scans using the AADC tracer [(18)F]fluoro-L-m-tyrosine (FMT) were performed as a measure of gene expression. RESULTS: The gene therapy was well tolerated, but 1 symptomatic and 2 asymptomatic intracranial hemorrhages followed the operative procedure. Total and motor rating scales improved in both cohorts. Motor diaries also showed increased on-time and reduced off-time without increased "on" time dyskinesia. At 6 months, FMT PET showed a 30% increase of putaminal uptake in the low-dose cohort and a 75% increase in the high-dose cohort. CONCLUSION: This study provides class IV evidence that bilateral intrastriatal infusion of adeno-associated viral type 2 vector containing the human AADC gene improves mean scores on the Unified Parkinson's Disease Rating Scale by approximately 30% in the on and off states, but the surgical procedure may be associated with an increased risk of intracranial hemorrhage and self-limited headache.

PMID: 19828868 [PubMed - as supplied by publisher]

it's not safe or there would not be so many adverse events. There are many. We haven't heard about all of them.

DBS is not safe enough either but it's the only choice. we asked for a treatment with gdnf /pump for this specific reason. the dose could be controlled-it could be stopped. the cell therapy and gene therapy are just not ready for prime time and won't be in our lifetime, [some of us]

Still think it's all bush's fault? how convenient for everyone else.

we get carrots dangled in front of our faces and go chasing them. we need to fill the trials but:
don't like what is being offered - we've had enough of following the business and pharmaceutical "new definitions" of our disease, which we would embrace if anyone would actually produce a treatment for other symptoms. aricept almost killed me..
i take amantadine and levo-dopa, nortriptylline, synthoid, nexium [it is better and if it's the placebo who cares?] see anything recently developed except the purple pill?

i've had enough of leaving the decisions of what to research up to people who are not involved with us, who don't care and know less than we do intuitively and from being around for awhile now.

patients can get comfortable in a parkinson career too. and they love it without getting paid because we are so damn interesting. it's such a humbling experience. but those who "get it" need to speak up now. it's not about you completely but we have been fed the same line for years about physicians being correct..

well it is largely about you. you know - the one who pays them all to ignore you; the ones who have to educate everyone because companies and drug reps don't keep private doctors and their patients informed about clinical trials? if more knew, more would see that the choices are few and they don't really work.

But at least they give the doctors stuff, for which the doctors will have to take the heat in a lawsuit.

That was the gdnf judge's conclusion, legally the patients did not have a relationship with the company.it was the investigators who were in a relationship with the 'subjects". they were the ones who could be sued.

.the "subjects" didn't agree.

there is just too much information for anyone to be up to date all the time but we can be ,because we are disease focused. we know there is much that is not shared. i have a few suggestions and would love more ..we need to reach our doctors, who are stressed and being robbed by eneryone else at the table and given gifts to recruit for trials. shouldn't it be the sponsors and doctors who educate us about trials?

it should go with out saying, that there are many good doctors but change is needd or we should all just stop trying.

it's hard to feel badly , as one honest and direct md with pd said, when a doctor only makes $300,000 instead of $500,000.

it's the reason for this that does make me upset. there are parasites feeding off of these doctors - insurance companies and lawsuits [that means attorneys and patients]. the vicious circles.

does anyone ever make short term goals? like for next week, tomorrow, next month?

what kind of progress will we see in six months? can you work faster? should have put the brakes on the Delorean about 6 years ago - missed the target. Can we go Back to the Reasonable Future?

I am not talking to mjff - i'm using language that, coincidentally, and universally can be related to by all stakeholders?

will there be a new treatment within the next year? how many hours a day is being spent on this study? how often does the IRB check in? There are already answers to some of these questions but we usually see failure or no results at all. regulations are not followed.

remember, the community is invited to make the ending of the Neurotalk Guide to the Parapatetic Pursuit of Parkinson's. It's a short term goal. it will be written by those who make it. no one is looking to be a star.....the window is too short and the pay is lousy.

young onset have a much larger window tho to learn the whole picture and it isn't pretty. not to be confused with not being blessed and leading good lives, which we can do very effectively when all on the same page. the ranks are larger now. 50 people just went through the Clinical Research Learning Institute and now there are close to 100 [just that i know of around PDF who are out there educating about[not selling] clinical trials.

now how about giving us something that is worth trying NOW.

does anyone have any news from Andy Grove? He is needed and we are not looking for his money.

sorry to sound like I'm boasting or bossy about being so bleepin' experienced with parkinson's.

don't know why signature didn't show up so now i'll probably end up with two.

paula
"I've never had advanced pd before."
"Tme is not neutral."