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PDCC Minutes - November 8, 2004

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Dr. Landis opened the meeting by welcoming the participants and discussed the overall importance of keeping track of what the different IC's are doing in PD to ensure that we don't have redundant efforts. She also commented that the PDCC is the model that many are using to track initiatives for various other disease portfolios across NIH because it is easy and inexpensive to do.

Roundtable discussion of initiatives:

NIDCD

Dr. James Battey explained that NIDCD is primarily interested in supporting research on PD when it becomes a communication disorder or involves problems with speech or swallowing. A clinical trial in progress will study the benefits of "thick liquids" (which are claimed to reduce aspiration) in individuals with swallowing disorders. The thick liquids are less than appealing as primary nutrition for patients, and data to date suggest that they may not provide a health benefit; PDCC will be informed as to the outcome of the trial. Dr. Battey also reiterated the importance of evidence-based medicine to inform our standards of clinical care. It was suggested that NINR be made aware of this important effort.

NIDA

Dr. Nancy Pilotte reported on several workshops held on brain resilience and repair, one of which featured discussions of PD models from investigators like Drs. Mike Zigmond and Tim Schallert (there were 18 speakers in total). NIDA also sponsored a mini-symposium on this topic at SFN, featuring Dr. Ole Isacson. Another workshop at the American College of Neuropsychopharmacology next year is planned.

Dr. Barry Hoffer reported on 4 NIDA intramural efforts related to PD. The first is investigating trophic factors other than GDNF in PD rodent models, including TGF-beta and the bone morphogenic proteins, BMP7 and BMP8. A second project, involving George Uhl, in collaboration with the Mayo clinic, is an association study using Affymetrix technology. The two other projects involve collaborations with the Karolinska Institute. One is a candidate gene study of the aldehyde dehydrogenase family where retinoic acids are altered in the nigra; the other is the development of a mouse defective in mitochondrial complex enzyme activity, exhibiting progressive neurodegeneration. The latter effort may yield a more physiological model of PD than the chemical lesion acute models.

NIMH

Dr. Debra Babcock reported that NIMH has a strong interest in the overlap of the circuitry affect by PD vs. that seen in mood disorders. Dr. Weinberger in the intramural program is working on the role of COMT in schizophrenia; it appears that COMT, in the frontal lobe, is as active as MAO. It is commonly thought that schizophrenia involves too much dopamine, while PD involves too little, but it is important to characterize the underlying circuitry and chemistry to determine overlap. Dr. Weinberger is working with Dr. Mark Hallett and it was suggested he may also want to work with Karen Berman. It was noted that some individuals who receive DBS do not improve overall unless their depressive symptoms are treated. They also noted they are planning a workshop on this for spring 2005.

NIA

Dr. Tony Phelps reported the outcome recommendations from the LBD/PDD workshop held this fall by NIA/NINDS, most notably a recommendation to the McKeith group to publish their criteria, and to set up several working groups on additional clinical data elements. (http://www.ninds.nih.gov/funding/areas/neurodegeneration/cpc_minutes_2004.htm )

The Philly group plans to submit a grant application for a follow up consensus meeting as a satellite to the WPC in 2006. They were advised strongly to include the McKeith group and Movement Disorder Society group to allow for a uniform agreement among all three.

Tony also mentioned the NIA RFA on Centers collaboration, and the fact that PD-DOC and NACC are working together. NACC has developed its uniform data set for the ADCs so all efforts will be made to utilize the same criteria across all centers. Secondly, NIA has implemented a new K award program based on congressional language from Congressman Markey (Markey Awards) which calls for training in neurodegenerative diseases including PD.

Dr. Judy Finkelstein mentioned NIA participation in the DBS effort, including the DBS activities at the upcoming neural prosthesis workshop. NIA has also funded a grant on biomarkers for PD which was received through their proteomics initiative. Lastly, the new gene finding from Dr. Singleton in the NIA intramural program was discussed, including the potential to have another "Cell Biology of PD" workshop, as have been held previously to capitalize on the newest, and collected, genetic findings to date.

NCCAM

Dr. Nancy Pearson described the NCCAM center at Emory, emphasizing several components; they are investigating the potential benefit of Valerian use in sleep and PD, tai chi for balance and gait abnormalities in PD, and transcranial magnetic stimulation (TMS) for PD. In addition, the admin core of this center is offering postdoctoral or other training awards ($35K/yr) for pilot projects. She will keep the PDCC apprised of these, as some may develop into R21's that will go to other IC's. The study of SAMe in depression in PD is ongoing. Lastly NCCAM is searching for an intramural scientific director and is welcoming suggestions of neuroscientist candidates.

NCRR

Dr. Franziska Grieder gave an update on the primate center at Wisconsin. They are expanding their program to include experts in stem cell biology and in other diverse scientific areas. PD models are created in rhesus macaques with MPTP, and they are exploring both DBS and PET imaging. The GCRC repositories for mouse models are continuing as usual.

NHGRI

Aideen McInerney described the collaborations between the Nussbaum lab and the European PD groups which led to the discovery of PINK1. They are now investigating the role of PINK1 in modulating levels of alpha-synuclein as well as studying the role of mitochondria in the PD. She also described the new findings of Dr. Andy Singleton on DRDN and mentioned that three families ascertained by the Nussbaum lab have DRDN mutations. They will soon be publishing on a new mouse model which features expression of mutated human synuclein on a homozygous knockout background.

NIEHS

Dr. Cindy Lawler announced that NIEHS now has a new director, Dr. David Schwartz from Duke, who will start in April. They are in the second year of the PAS on gene-environment interactions (recall that year 1 was devoted to ALS, year 2 will be expanded to other neurodegenerative diseases as recommended by their advisory committee meeting). They have also completed the R21 program on the fetal basis of disease; two awards have been made on the prenatal origins of PD. A competitive supplement program is in place for the CCPDER centers that allows for projects across centers; so far these include screening to look at new environmental agents and creation of a rotenone model in primates. An administrative supplement has been awarded for a series of meetings to develop criteria for epidemiology of PD -- these will be eventually incorporated into PD-DOC.

The CCPDER program is in its third year so NIEHS will begin an evaluation process to determine if and how they should be recompeted. (Note: Dr. Melinda Kelley briefly described the evaluation process that will happen with the Udall centers program, beginning with a feasibility study that should lead to a full-scale evaluation of the centers. By contracting an outside group, it is hoped that internal bias will be avoided. The review should be complete by next year.)

DOD

Dr. Stephen Grate mentioned that DOD currently is funding 136 projects related to PD. Mark Hallett and Ole Isacson have some specific projects that warranted additional consideration by DOD. In keeping with this, they intend to create series of advisory panels which they hope will make the programmatic process smoother. The panels will include 1) scientific experts in PD; 2) federal advisors; and 3) advocate representatives.

A brief discussion of the role of stakeholders in planning and decision-making ensued. Dr. Battey described a very successful approach that NIDCD has used which includes the collection of a 2 page write up from each of the voluntary groups, and offering them 5 minute presentations at the beginning of scientific advisory meetings. In this way, the scientists may deliberate and include the opinions and needs of the advocate community in their priority setting.

NINDS

Dr. Diane Murphy thanked all of the institute representatives for sending their PD grants lists for FY03 -- this information is now all up on the web for those interested. NINDS has 3 areas in which the help and participation of the other IC's are welcomed: 1) FY04 grant lists when coding is completed; 2) There will be a portfolio analysis meeting (primarily for the advocates to give their input) directly following the Udall centers meeting to which all NIH reps are invited; and 3) planning for the PD Summit of 2005.

Dr. Paul Sheehy noted that the Stem Cell RFA is out which encourages translational centers. It is hoped that this effort will push NIH stem cell efforts ahead by bringing together those of different disciplines. The idea is to create teams of people that normally wouldn't interact to get stem cells into sophisticated animal models for testing and finally to Phase I clinical trials. A pre-application meeting will be help on Dec. 10th from 9-12 in building 31.

Ms Marian Emr gave a short presentation on the progress of the WPC, scheduled for February 2006 (cards with the WPC website and dates were provided). Various committees have been formed for meeting planning and an R13 proposal will come in to NINDS in December requesting meeting support from all interested IC's. The DOD has committed funds to this effort as well. There has been some tension regarding the level of science vs. patient education aspects of the congress -- they have decided to double the scientific content of the meeting to ensure full participation from the research community.

A brief update on the NINDS genetics repository was presented. The repository has exceeded its goals in the first 2 years and hundreds of samples are available for use by investigators, as well as case-control series. There was discussion of the definition of controls, and it was noted that if controls could be combined across existing repositories, it would enrich all of them. NACC has 1000 controls already. It was suggested that MJFF be encouraged to have stronger requirements for sharing samples.

Dr. Finkelstein discussed a meeting held by NIMH to try to develop sharing standards that could be put in place for deCode applications. Because these samples cannot leave Iceland, it is a unique situation; genome wide SNP analysis can be shared in silico, but samples cannot. NIEHS will check on the sharing status of the Emory CCPDER currently collaborating with deCode.

Paul Sheehy also noted that the animal model repository at UCLA has models ready for use, including DJ-1, alpha-synuclein KO, and alpha-synuclein over expression model. It was suggested that models created through MJFF grants should also be shared, and that the use of frozen embryos for repositories may be an easy and inexpensive way to allow sharing.

Last updated February 09, 2005