On Friday the 13th, if you are superstitious, I spoke with Howard Federoff, a leading Neurologist and clinical scientist. He is also Dean of Georgetown Medical School, and as Chair of the NIH recombinant DNA advisory committee, he was instrumental in setting up the 2010 NIH workshop on the use of sham control groups in double blind research designs. (The report from that conference should be published shortly.) It has been 3 years since Dr Federoff first told me about the interests of the Gene Therapy Study Group consortium, an academic group of PD researchers that he leads, in developing GDNF gene therapy. I have been checking in with him on a regular basis to get updates from the top and to offer patient advocate assistance wherever possible (e.g. to help communicate with PWP or FDA), as well as to be a squeaky wheel.
Now after 7 years since Amgen declared GDNF unsafe and ineffective, we may be starting to see real movement. After all the work that many of us did to try to coax Amgen to continue development of GDNF therapy, this is the prize. Although it has been slow, we are fortunate that there are people with the stature and ability of Dr. Federoff and his colleagues to pursue this development, given the limited IP protection (Amgen's original patent runs out this year). Funding the later phases will continue to be a challenge as will the methodology for well controlled trials required by regulation and the "sham wall" (see Katsnelson "Why Fake It" Nature , Aug 10, 2011.
http://www.nature.com/news/2011/1108...l/476142a.html and Benderly "Head Games" Miller-McCune, Jan 2012
http://www.miller-mccune.com/health/...thought-38717/ ) that we have observed in the evaluation of past surgically delivered therapies.
Dr Federoff said that the IND (Investigational New Drug) application for the GDNF-gene therapy was complete and would soon be submitted. During the 3 years since this planning began, the researchers have conducted long term toxicology studies on GDNF in primates, and have exhaustively documented all aspectes of the science and research with evidence from preclinical research. Then over the past 6 months they have prepared the IND package. After it is submitted, the FDA has 30 days to put a hold on starting the trial or the trial can proceed without further approval. Given the track record for successful clinical development of new PD therapies, maybe such meticulous effort is necessary to achieve the sucessful outcome we all desire, but as I told him, being a patient with a servious illness takes a lot of patience.
More than a year ago,I had spoken to the NIH neuro-surgeon, Dr Russell Lonser, who will implant the GDNF-AAV virus, who said they already had IRB approval. I dont know what are the other procedures that need to be scheduled other than the informed consent so they could start operating by March if everything goes smoothly, but it seems like it never does. I do not know what the schedule is for subsequent surgeries.
Dr. Federoff also said they already had several people lined up to participate. A number of PWP have been doing a 6 month test of the At-home measurement device developed by the Kinetics Foundation to be used along with clinical neurological examinations and neuro-psychology tests to provide quantitative measures in the evaluation of the outcomes. The 6 months of data will provide a stable baseline assessment of the starting point for patients and will lead into participation in the clinical intervention, inserting the virus in the putamin, for this phase I/II study. Patients will be randomly assigned to one of four groups of 6 patients each to test the safety of each dose level and provide a first look at improvements from the baseline.
Some of us were worried that the announcement on the phase II study of direct infusion of the GDNF molecule might be a signal of a change in priority of the study team, but this appears to not be the case here, if in fact there are no further delays. This other phase II study will be done in Bristol UK, with Dr Steven Gill.
Perry