Last Thursday’s (11/5/09) CurePSP webinar with Dr. Yvette Bordelon was definitely a winner! Not only was the speaker excellent but the material covered has not been made available to laypeople by an expert in the field in this consolidated manner previously.
I had two issues with the content of Dr. Bordelon’s presentation: she seems relatively uninformed about the davunetide (NAP) study in PSP and CBD, and about the Azilect study in MSA-P.
I appreciate the fact that the CurePSP introductory information was completely different from the previous webinars. This certainly makes the repeat of the fundraising message in the middle of the webinar far more tolerable.
One item of improvement to the webinars overall remains on my wish list since the Hermanowicz webinar in early October: the questions given during the Q&A need to be consolidated and massaged. It is so frustrating to hear questions brought up along the lines of “what treatments are available now,” when the speaker just covered that very question. CurePSP needs a totally different approach to the Q&A section.
Also, while I thought the Schellenberg info on the genetics in PSP and CBD was great to hear, it really warranted it’s own (shorter) webinar and, of course, was not relevant to the MSA attendees. (I have posted my Schellenberg notes separately.)
What follows are my notes on Dr. Bordelon’s presentation and the Q&A session following. As this is being posted to PSP and CBD online groups, I’ve maintained the info on PSP and CBD, and shortened the info on MSA. I’ve added lots of my own notes, especially about the various trials underway and in the pipeline. I’ve added some headings, and re-organized the Q&A section.
Neurologist and Movement Disorder Specialist at UCLA
Her clinical research is focused on biomarkers.
Translational research: how does lab research (“bench research”) get translated into the clinical setting?
In the lab: basic science; pre-clinical trials in animals
In the clinic: clinical trials
The outcome of all of this research are new treatments
Who is affected
What is the pathology
When does it begin
Where is the pathology
Why does it occur and what are the consequences
Who and when:
PSP: 6 per 100K prevalence; average age of onset is mid-60s
CBD: 4-5 per 100K; average age of onset is mid-60s
MSA: 3-4 per 100K; average age of onset is early 50s
For comparison, PD: 500 per 100K; average age of onset late 50s
[Robin’s note: I could believe 1-2 per 100K for CBD, but not 4-5, especially when that’s higher than MSA. I think Dr. Golbe said CBD prevalence hadn’t been studied so I’m curious as to the source of Dr. Bordelon’s figures.]
These are disorders of abnormal protein accumulation in the brain. In all neurodegenerative disorders there is cell loss in the brain.
What is the pathology:
PSP and CBD: tau protein
MSA: alpha-synuclein protein
Alzheimer’s Disease: tau protein and amyloid protein
Parkinson’s Disease: alpha-synuclein protein
Where: the location and type of protein that accumulates determines the disease. Parkinsonism symptoms are produced in the brain when there is protein accumulation in the brain stem and basal ganglia.
PSP: some places where tau accumulates are the brain stem, basal ganglia, the frontal lobe (cortex), and the cerebellum. (Frontal lobe pathology may lead to issues with multi-tasking, higher level cognitive functions, and apathy. Cerebellum pathology leads to issues with balance.)
CBD: some places where tau accumulates are the brain stem (a much smaller area compared to PSP), basal ganglia, and the cortex (a much larger area compared to PSP and a different area than PSP; the parietal area of the cortex is affected). The pathology in CBD is asymmetric – one side of the brain is more affected than the other side. This is why one side of the body usually has more symptoms initially than the other side. (The parietal area corresponds to how we figure out how to do things. This is why apraxia is a problem in CBD.)
MSA: some places where alpha-synuclein accumulates are the brain stem (a much larger area than PSP and different areas than PSP), basal ganglia, and the cerebellum (a much larger area compared to PSP). One area of the brain stem affected in MSA is called the pons. Ataxia or difficulty walking and balance problems are related to pathology in the pons and cerebellum. Other brain stem areas are responsible for blood pressure control and other symptoms we see with MSA.
Why: identification of risk factors for these three disorders
Genes: we think that genes contribute to this
Environmental exposure or experience in general: play a large role
The overlap or interaction between genes and the environment is where the true risk factors lie.
There are other risk factors yet to be determined.
* sticky proteins: clumps; accumulation
* clearance problem: the cell can’t get rid of the sticky proteins
* further consequences: decreased energy stores (mitochondria are sick or diseased); inflammation (inflammatory cells invade the brain; these cells secrete cytokines or other proteins that may be toxic); cell death (neurons die)
Genetic causes of PSP and CBD:
* The only genetically confirmed finding from research: certain version of tau (the H1 haplotype) confer a greater risk in PSP and CBD. In those with PSP and CBD, the H1:H2 ratio is 3:1. In the general population, there is a 1:1 ratio.
* Direct inheritance of any atypical parkinsonian syndrome is extremely rare. But there have been isolated cases of families where tau, parkin, or LRRK2 genetic mutations in PSP are inherited. Examining these isolated cases helps us determine causes.
Ongoing genetics research:
* Genes that make someone susceptible (a) in combination with other genes, and (b) in certain situations (given environmental exposure)
* Example of PD: if someone has pesticide exposure and a gene that causes them to metabolize these toxins more slowly, their risk of developing PD is increased
* There are genome-wide screens going on for all these diseases
Clusters of diseases can guide our research into environmental risk factors. Two PSP clusters are:
* Atypical parkinsonism of Guadeloupe. Linked to the ingestion of pawpaw fruit and boldo tea, which contain a high level of toxins. Most of these patients with this exposure have the H1 haplotype. Double typical prevalence of PSP. This is an example of the interplay of genetics and the environment.
* Lytico-Bodig disease (aka, Parkinsonism-dementia complex of Guam). No definitive environmental exposure identified yet. Possible exposures are: guano from the fruit bat, cycad seeds (ingested by the bat), and aluminum
RISK FACTORS – CLINICAL TRIALS
Two clinical trials are underway to identify risk factors:
#1: PSP – “Genetic and Environmental Risk Factors,” organized by Dr. Irene Litvan. 12 sites in the US (including UCLA and the Univ of Washington in Seattle) and 1 site in Canada. (For a complete list of sites, see pspstudy.com.)
This study wants to enroll 500 PSP patients and 1000 controls. More participants are needed! If the study does not meet its recruitment goal, the data may not reach statistical significance. Further, the study may not be eligible for continued NIH funding if recruitment remains low.
Patient requirements: clinically diagnosed PSP; 40 years of age or older; able to participate in a 25-40 minute phone interview; can visit one of the screening sites; no other major neurological disorders. Note: patients are no longer required to bring two healthy controls into the study with them.
Study involves: neurologic exam, past history, blood draw for genetics research, consideration of brain donation.
Contact the study team directly: pspstudy.com, phone 866-PSP-0448
#2: PSP and MSA – “Neuroprotection and Natural History in Parkinson’s Plus Syndromes,” NNIPPS, Dr. Peter Leigh (UK). 44 sites in Europe (UK, Germany and France).
[Robin’s note: I first learned about NNIPPS in June, and may’ve posted about it at that time. This 3-year longitudinal natural history study is attempting to establish a database of early diagnostic criteria. I believe the study is limited to PSP and MSA; I don’t think CBD is included. The NNIPPS study group is the team that already investigated the use of riluzole in PSP and MSA.]
GENOME WIDE SCREENS
Genome wide screens:
* Search for genes in all patients with these disorders
* These screens are happening in the ongoing observational studies
* PSP and CBD: One specific genome-wide screen that is taking place is the Peebler PSP and CBD Genetics Program, headed by Dr. Jerry Schellenberg, involving researchers in the US, UK, and Germany.
* These screens will contribute to our understanding of the genetics and environmental factors with these disorders
Tau protein accumulation in PSP and CBD:
Tau becomes modified (hyperphosphorylated), making it sticky. This clumps. Accumulates in brain cells called neurons and other cells; these accumulations or clumps are called “tangles.” Tau loses its usual beneficial effect of strengthening the neuron. These accumulations lead to cell death.
One reason protein accumulation in the brain occurs is because the machinery to dispose of the garbage protein is dysfunctional. Autophagy does not occur.
* Loss of cellular energy supplies due to the generation of free radicals (or oxidants) that attack the mitochondria, making it dysfunctional. (The free radicals are generated in reaction to the clumped protein.) With dysfunctional mitochondria, the cells cannot keep up its energy supplies.
* Neuroinflammation. Microglial cells are indicators of inflammation.
* Eventual cell death.
Animal model research:
* Animal models increase our understanding of the causes of disease: genes, toxins and pathways are identified
* Screen for possible treatments: pre-clinical trials
* PSP and CBD: expression of tau mutation in mice
* MSA: over-expression of alpha-synuclein in mice. There is even a model that specifically allows over-expression of alpha-synuclein in oligodendroglial cells (the support cells).
* We don’t have adequate biomarkers of these diseases, which is why we need animal models.
Biomarkers: biological characteristics that are objectively measured that indicate the pathogenic cause of a disease or a pharmacological process (treatment of disease). Examples: lab tests, brain imaging. These lead to earlier disease detection. They are a “window into the brain.” Ideally, biomarkers can serve as a substitute for a clinically meaningful endpoint that delays or stops disease and will predict clinical benefit. Biomarkers would optimize clinical trials: trials would be shorter (weeks/months rather than months/years) and more effective.
Brain MRI is an effective biomarker. Brain MRI can possibly reveal focal brainstem atrophy (volume loss) in atypical parkinsonism syndromes. The MRI examples shown were for PD, PSP, and MSA. (Oba, et al, Neurology 2005)
[Robin’s note: the Oba 2005 abstract is one of the first I ever circulated to online support groups. You can find the abstract on pubmed.gov, for free, using PubMed ID# 15985570. The authors’ conclusion was: “The area of the midbrain on mid-sagittal MRI can differentiate PSP from PD, MSA-P, and normal aging.”]
Another biomarker: measuring MRI focal atrophy over time. The NNIPPS study found that the rate of midbrain atrophy in PSP is 7x faster than controls while the rate of pontine atrophy in MSA is 20x faster than controls.
[Robin’s note: This data comes from a 2007 article published by Pavouir, et al.]
Another biomarker: PET (positron emission tomography) scans. PET scans allow for functional imaging; they show how the brain works (metabolism). In the CBD PET scan shown, one side of the frontal lobe and one side of the parietal lobe have decreased functioning. The asymmetric nature of CBD is clear.
[All of this biomarker data, plus some additional biomarker info Dr. Bordelon didn’t review, is nicely summarized in a March 2009 medical journal article. You can find the abstract on pubmed.gov using PubMed ID# 19364361.]
Future research into the use of blood and spinal fluid measures as biomarkers. Can we measure the proteins that are accumulating or other downstream consequences? Example: lots of studies of spinal fluid in Alzheimer’s Disease are being replicated in the atypical parkinsonism community.
Future research into the use of imaging biomarkers to label protein accumulation in the brain. Example: amyloid ligands for PET scanning. (Ligands are agents that serve as markers.) The PET scan image shown is of an MSA patient with markers for protein accumulation lit up in the basal ganglia of the brain. [Dr. Bordelon described amyloid as a general term meaning protein accumulation in the brain. Robin’s note: this is confusing because I thought amyloid was a specific type of protein.]
TREATMENT – NEUROPROTECTIVE
Three treatment categories: Neuroprotective, Restorative, Symptomatic
Neuroprotective approaches: the goal is to modify, slow, or stop disease progression over time. Currently, we can make a diagnosis after symptoms develop.
Four examples of neuroprotective studies that are underway: (ten years ago we couldn’t say that we were trying to modify the course of these disorders)
#3 PSP – Pyruvate, Creatine and Niacinamide: Dr. Litvan, Univ of Louisville; acts on energy supply pathway in brain
[This trial is not currently recruiting. See http://clinicaltrials.gov/ct2/show/NCT00605930 In this study, those receiving the supplements will get “A bar of 2 gm of pyruvate and 1 gm of creatine, and a pill of 1 gm of niacinamide once a day for 24 weeks.”]
#4 PSP and CBD – Coenzyme Q10: Dr. Apuertenova, Lahey Clinic (Boston); acts on energy supply pathway in brain
[This trial is currently recruiting. See http://clinicaltrials.gov/ct2/show/NCT00382824 The last time I talked to Stephanie Scala at Lahey Clinic about this, the dose given was 2400mg/day and they were using the Vitaline brand. A fair amount has been posted about CoQ10 and this Lahey Clinic study on the PSP Forum: http://forum.psp.org/viewtopic.php?t=3042]
[Stephanie Scala at Lahey Clinic also told me that CoQ10 was being studied in MSA with a dose of 1200mg/day. This study wasn’t listed on clinicaltrials.gov.]
#5 PSP and CBD – Lithium: NIH-sponsored, multi-site; acts on tau phosphorylation-GSK-3 specifically; no longer recruiting due to toxicity issues
[In late August, local support group member Phil told us that NIH had cancelled the lithium trial. His wife Jackie, participating in the trial at Oregon Health & Science University in Portland, had experienced severe side effects. See dosing and titration info at http://www.clinicaltrials.gov/ct2/show/NCT00703677]
#6 MSA – Intravenous Immunoglobulin: Dr. Peter Novak, Univ of MA; acts on neuro-inflammation pathway in brain.
[This IVIg trial is currently recruiting. See http://clinicaltrials.gov/ct2/show/NCT00750867]
Two neuroprotective clinical trials will start in 2010:
#7 PSP – TAUROS (which stands for “Tau Restoration in PSP”): using a new drug called Nypta, developed by Noscira (based in Madrid). Acts on tau phosphorylation (“the stickiness”) and GSK-3. Researchers are hoping this drug will not have the problematic toxicity of lithium. Both lithium and Nypta are acting on the enzyme GSK-3 but Nypta is a more specific inhibitor of GSK-3. Nypta is a more pure inhibitor of this phosphorylation mechanism than lithium.
This is a phase II (safety/tolerability), double-blind, placebo-controlled study. Participants will be randomized to receive 600mg Nypta, 800mg Nypta, or a placebo for 52 weeks. Biomarkers: MRI at some of the European sites; an optional spinal fluid test will be available at all sites.
Multi-center study in Spain, UK, Germany, and US. US sites participating include: UCLA, Robert Wood Johnson Medical School (New Brunswick, NJ), Univ of Louisville (KY), Univ of South Florida, Univ of Colorado, Mayo Clinic (Jacksonville, FL), and Parkinson’s and Movement Disorders Institute (Fountain Valley, CA).
There was a big investigators meeting this week. The study will enroll in early 2010.
[Dr. Bordelon said the “University of Maryland in New Jersey in New Brunswick” is participating. I think this is a misreading of “UMDNJ.” UMDNJ = University of Medicine & Dentistry of NJ. The Robert Wood Johnson Medical School is one of the schools of UMDNJ. Dr. Lawrence Golbe is based at RWJMS.]
[Noscira is a unit of the company Zeltia. Here’s a short Reuters news story from 11/3/09 about Zeltia’s drug Nypta receiving orphan drug status in the US and Europe: http://www.reuters.com/article/rbssIndu … 1320091103]
[There is a short bit of info about PSP on the manufacturer’s website: http://www.noscira.com/investigacion.cfm?mS=226&mSS=555 This says nothing about Nypta.]
[Update on 11/9/09: Mayo Jax has asked one of its PSP patients to come in for an evaluation appointment in February 2010, presumably for this study. Just because Mayo Jax is participating in this study does NOT mean that Mayo Rochester or Mayo Phoenix is participating.]
#8 PSP – Davunetide, a new drug developed by Allon Therapeutics. This drug also acts on tau phosphorylation but through a different mechanism. It also enhances cell survival (a second mechanism).
This is a phase II (safety/tolerability), double-blind, placebo-controlled study. Participants will be randomized to receive Davunetide (intranasal) or a placebo for 52 weeks. Biomarkers: MRI and spinal fluid.
She believes there will be sites in Spain, Germany, UK and US, but these sites are not confirmed yet. This study will likely start in spring or summer of 2010.
[Dr. Bordelon described Allon Therapeutics as being a US company. It’s a Canadian company, based in Vancouver. You can find some info on this experimental drug from http://allontherapeutics.com/]
[Davunetide is also called NAP (AL-108). My assumption is that the US sites will be UCSF (lead site), Mayo Rochester, and UPenn, as these were the sites planning to study NAP in 2009 through a CurePSP grant. That CurePSP grant was to study NAP in both CBD and PSP. Dr. Bordelon only mentioned PSP, and she didn’t mention this history with the CurePSP-funded NAP study being led by UCSF.]
Basic mechanisms and animal models are being used in the lab. The hope is that this lab research now in the pipeline will turn into neuroprotective clinical trials. This lab research targets:
* prevention of protein misfolding
* acceleration of clearance of protein aggregates
* stabilization of brain cell function. How do we stabilize tau and the microtubules that it supports? Or how do we stimulate growth factors for the overall health of the cell?
* enhancement of cell energy production through free radical scavengers (antioxidants)
TREATMENT – RESTORATIVE
Restorative treatment: stem cell treatment. California Institute for Regenerative Medicine has funded two studies of stem cell treatments — in PD and Huntington disease. Once optimized, these findings can be applied to other diseases, including atypical parkinsonism disorders. These CIRM-funded studies, now underway, are looking at:
* the type of stem cells that can be best used, including iPS
* delivery system: direct surgical implantation (which is our current system) and blood delivery to target the right area of the brain (which is under development)
* prevention of rejection of cells
* keeping stem cells healthy
* directing stem cells to develop neurons
Another restorative treatments under investigation: delivery of Growth Factors to damaged areas of brain. Growth Factors are signals to neurons to grow and repair. GFs are in very high abundance during brain development, in the embryonic stage. How can we re-activate the GFs once the brain has begun to degenerate? There are currently clinical trials for this in Parkinson’s Disease and other disorders.
Another restorative treatments under investigation: activating the brain’s own stem cells to grow into the damaged areas. We didn’t know until recently that the brain has its own supply of stem cells in the area where CSF is contained. This is a rich source.
Another restorative treatments under investigation: working at the genetic level to turn off genes that cause disease. The technique is called RNAi. (i=interference) RNA is part of the genetic code. Significant progress for neurological diseases has been made in this area.
TREATMENT – SYMPTOMATIC
Symptomatic treatment. This area needs more and better study as we still don’t have great treatments for these problems:
* treating movement and cognitive problems
* gait and balance problems
* speech and swallowing
* incontinence and low BP
#9 PSP – DBS (deep brain stimulation), which is brain surgery. Research going on to use a novel target, the PPN (pedunculopontine nucleus), in PSP. The target in the brain (PPN) is very small. Only very experienced neurosurgeons could conduct this surgery. Dr. Lozano in Toronto is the lead investigator. This is CurePSP-funded.
[General info on this Canadian DBS study in PSP is here: http://forum.psp.org/viewtopic.php?t=7733]
#10 PSP and CBD – TMS (transcranial magnetic stimulation), which is a non-invasive therapy. The study includes three visits, each lasting three hours. These three visits can be accomplished in a one-week period, if necessary. Three different treatments are given: TMS for mood, TMS for movement, and one placebo (to rule out the placebo effect). Dr. Allan Wu at UCLA is the lead investigator. This is an active clinical trial that is currently recruiting patients; the contact at UCLA is phone 310/206-3356. This is CurePSP-funded.
[General info on this TMS study in PSP and CBD at UCLA is here: http://forum.psp.org/viewtopic.php?t=7732 I emailed the local support group on 8/24/09 to say that one member of our group participated in this treatment and saw “no results.” That email also indicated that there are some small studies of TMS going on in Parkinson’s Disease.]
#11 MSA – rasagiline (Azilect), a medication. There will be a trial in 2010. It is being organized by Teva Pharmaceutical, the manufacturer of Azilect. It is not yet enrolling. It will likely be a large, multi-center trial. This drug is currently being studied in PD for symptom control and neuroprotection.
There have been significant advances in our understanding of the causes of these 3 disorders.
Treatments are being designed, and are entering clinical trials.
The most likely treatment approach will be multi-pronged. (Example: using aggregation inhibitors, anti-oxidants, etc)
[See #1 to #11 above]
Visit clinicaltrials.gov, a portal for finding out about active research studies. Plug in keywords or a disease name.
Brain donation: one of the most significant contributions someone can make
QUESTIONS AND ANSWERS: (all answers are by Dr. Bordelon)
Question: What are the benefits of participating in a clinical trial? I have early-stage PSP.
Answer: Clinical trials are the only way of determining if a medication is effective. An example is the CoQ10 clinical trial. It’s our only way of determining if CoQ10 is effective.
Clinical trials can be helpful in understanding risk factors for diseases.
The drug or treatment being studied may have direct benefit or improvement of symptoms. For example, both DBS and TMS offer the possibility of improvement of symptoms to trial participants.
In a trial of experimental medication, some participants will be taking a placebo. Depending on the regulatory agency, those participants taking a placebo may be able to access an “open-label extension,” if the drug is determined to be safe. This means they would have access to the experimental medication.
The risk of a drug trial is that the drug might not work or might worsen the disease.
In summary, why participate? Because it might benefit you and increases the chance that effective treatments may be found. And participation increases our knowledge about these diseases. It may have a beneficial effect for others who may be affected with these disorders.
Question: How can we contribute (time, effort, and money) towards a research program that might discover some treatment or a cure? We are dealing with MSA.
Answer: Directly participating in a clinical study has a significant contribution.
Educating people around you about the disorder you are facing is helpful and important. This increases awareness in the community.
Advocacy to members of congress in US is helpful and important. Congress controls the budget of the NIH, which is key to neuroscience research in the US. Another example: there is a bill currently going through Congress about a Parkinson’s Disease Registry. Such a registry may have benefit for atypical parkinsonism disorders as well.
Brain donation is one of the most significant contributions anyone can make. This establishes a diagnosis and helps research studies that are underway to determine causes.
Fundraising is important.
Question: What are the benefits of brain donation to future generations?
Answer: This is one of the greatest gifts someone can make towards research.
MDs are uncomfortable asking about this.
See psp.org for info. [http://psp.org/page/braindonation]
Speak with your MD about this.
Incorporate brain donation into your living will.
Question: Has any of the research led to a medication or a surgical treatment?
Answer: We are hopeful that in time this will happen.
Question: What over-the-counter (OTC) treatments are available or what treatments are available that don’t require participating in a clinical trial? I have either PSP or MSA.
Related Question: What is CoQ10 used for?
Answer: CoQ10 and creatine are available OTC, considered generally safe, and are well-tolerated. They can be added to a medication regimen. Discuss this with your neurologist or general practitioner. If you have liver problems, be cautious with creatine.
CoQ10 dosing should be 1200 mg/day (taken as: 400mg 3x/day, or 600mg 2x/day).
Creatine dosing should be 5 grams 2x/day.
Neither CoQ10 nor creatine have been studied in atypical parkinsonism disorders. None of the trials in Parkinson’s Disease clearly shows these supplements work but the data are intriguing such that that these supplements continue to be studied. An early study of CoQ10 in PD showed it may have mild benefit for symptoms.
With these supplements, you are not looking for symptom control. You are looking for neuroprotection (slowing down disease). This means you may not see a direct benefit. Don’t stop the drug if you don’t see direct benefit because these supplements don’t work that way.
Question: What are the effects of exercise? Are any types of exercise recommended?
Answer: Exercise is incredibly important. It should be emphasized as much as medications, if not more. It must be done in a safe fashion. Optimally, you should exercise daily. Select an exercise that is enjoyable and that you would want to do every day.
Good types of exercise promote flexibility, mobility, and keeping muscles in shape. Yoga and tai-chi can be helpful and important for balance and postural strengthening.
We think exercise is beneficial for the brain — that it’s neuroprotective. Exercise increases the release of Growth Factors in the brain.
Consultation with a PT can be helpful in determining an exercise regimen.
She has had patients whose balance has improved in PSP with exercise!
Question: MDs outside the US are making claims of cures for brain disorders. Should we seek out this treatment?
Answer: It depends on the claims. If the treatment is expensive, be cautious.
She asks her patients to run these claims by her (or an MD) as she’s concerned about harm.
Question: Is there any validation to the stem cell treatments in China, Russia, and Ukraine?
Answer: As yet, no studies show that stem cell treatments work. Be cautious. These are situations where we don’t know exactly what is going on.
Studies under investigation as to what stem cells should be used. Regimented research is needed. Clinical trials are needed.
She talked about the case of a Huntington Disease patient. After overseas stem cell treatment, the patient got signfiicantly worse. They were unable to get medical records from India as to what was given to this patient.
Run-away dyskinesias have been seen in some cases. We need to wait for studies into this to be sure these treatments are safe.
Currently stem cell treatments are not safe. Be cautious, especially given the high cost and no scientific evidence. These treatments might cause harm. Talk to your physician about this.
Question: What are the chances of passing down the atypical parkinsonian disorder to children or grandchildren?
Answer: Very rare. Only isolated families have passed this disorder along. In contrast: 10% of PD may be passed among family members.
11/19 – Golbe
12/3 – Jerome Lisk and panel