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 "What's in the PD Pipeline" - Archived Webcast 
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Post "What's in the PD Pipeline" - Archived Webcast
There was a Parkinson's Disease Foundation webcast on 5/9 covering these three topics:
* Genetic Lessons and New Approaches in Learning about Parkinson’s Diseases
* Recent and Future Innovation in the Treatment of Parkinson’s Disease
* Stem Cells and Gene Therapy for Parkinson’s Disease: Is the Cure on the Horizon?

Over the last month I've listened to these three lectures as well as the final Q&A session. I'd highly recommend watching parts of the archived webcast. In particular:

* The first topic included mere mentions of LBD, PSP, CBD, and MSA. The most interesting part of that first presentation was the Q&A as to whether your chance of having PD (or any related disorder) increases if you have a parent with PD.

* I'd recommend listening to the second presentation if you are interested in creatine, minocycline, and isradipine. And, during this presenter's Q&A, he gave useful advice on how to be a good consumer of healthcare and how to work with your MD. He also explained why SPECTs are not routinely available in the US.

* I'd highly recommend the third presentation just for a general background on what are stem cell transplants and gene therapy. I didn't understand it all but my knowledge-level has increased enormously just from that hour's presentation.

* The final Q&A (35 minutes) with all three presenters is terrific. Dr. Gwinn gave an interesting explanation for why lung infections are likely in PD, and how stretching can prevent these. Dr. Svendsen noted that 95% of stem cell therapy companies worldwide are charlatans. And he also indicated that neurons should not be our focus. Dr. Stacy talked about the public putting pressure on clinicians, researchers, and government to share data and find a cure. LBD was the subject of one of the questions.

Below, I've provided some notes from the presentations and Q&A sessions. Of course it's much better to watch the videos yourself! Go to:
http://event.netbriefings.com/event/pdf ... dpipeline/
In my notes, I've given some of the minute:second markings as to when a particular topic was raised.

Enjoy!


Some notes from:
Genetic Lessons and New Approaches in Learning about Parkinson’s Diseases
Katrina Gwinn, M.D., NIH/NINDS
Note: her presentation starts at 5:40 (after opening remarks, etc).

How will this research make a difference to patients in the long term?

Why study genes? Genes can give us clues about biological causes of diseases. Maybe 1-2% of all PD cases are purely, causally genetic. Looking at these cases can give us clues about the other cases of PD. Also, genes can be used to develop diagnostic tests and give us clues regarding therapeutic targets.

Two categories of genes: 1) the kind that, if inherited, causes PD, and 2) the kind that, if inherited, slightly increases the risk of PD. Not every genetic factor can cause a disease but it can increase your risk. Her example: she inherited her father's pale skin and this slightly increases her risk of skin cancer but it doesn't mean she'll get skin cancer.

There are many genetic causes of PD.

Sometimes the same gene can have a highly variable effect even within the same family. Example: one family member with a gene got PD at 24, and another family member with the same gene got LBD at 51. The "dose" of synuclein seems to be important. (There are double doses and triple doses.)

Genes can have different influences depending on the ethnic groups they are in.

Having the gene doesn't mean you'll get the disease. Not having it doesn't protect you. But having it increases your risk and not having it lowers your risk.

NET-PD trial underway. NINDS is looking at whether PD's progression can be slowed.

She thinks people would get genetic testing for PD (and other diseases) if there's some change they could make in their lives based on the data.

Symptoms occur after 70% of neurons in substantia nigra are lost. PET data suggests there's a pre-clinical stage to PD.

Not all people with RLS (restless legs syndrome) will get PD. In people who get PD, RLS is increased before people get sick (with PD).

Smell is abnormal in PD, but not in PSP, MSA, or CBD. If you do a screening (smell) test for this, there will be lots of false positives as people lose smell due to allergies, chronic colds, history of smoking, Alzheimer's Disease, etc.

Only small difference between early PD and normal controls on Beck Depression Inventory. So, she doesn't see depression as being a risk factor for PD.

Non-motor symptoms may or may not precede motor symptoms. Constipation? Skin problems? (Her dad had "cradle cap" at the age of 40. He later got PD.) Urinary hesitancy? Other autonomic? Pain and stiffness ("radicular symptoms" such as radiculopathy or sciatica). This last item - radicular symptoms - is based upon anecdotal evidence she has gathered. This all needs to be studied much more.

What are the genetic or environmental factors leading to earlier, later, milder, or more severe PD?


Question: Are there any markers to predict the rate of progression in PD?
Answer: Past performance is a predictor of future behavior. There seems to be a trajectory. PD is gradual. There are no overnight changes in PD. Some people say that if you have tremor, you have a better course. But these observations may have included people with PSP in the no-tremor category, thereby skewing the outcome. There is good data that shows that exercise affects the rate of progression. (More exercise slows progression.)

Question: Any relationship between narcolepsy and PD?
Answer: She's not personally aware of this.

Question: Any relationship between inflammation and PD?
Answer: People are starting to study this. We do know that in AD there's no doubt that inflammation plays a role.

Question: What is the increased risk of my sons getting PD if I have a father with PD and I have PD?
Answer: 4-9% increased risk over the general population. Keep in mind that a lifetime risk for cancer is 20%. So your sons have a greater risk of cancer than PD.

Question: Why would people who don't have tremor have a faster progression? My husband doesn't have tremor and it took the MDs a long time to diagnose him with PD.
Answer: We don't know. If someone doesn't have garden-variety or typical PD, maybe they are not diagnosed until later in the disease course and so they really don't have a faster progression. There are many types of Parkinson's Diseases. People have different symptoms.

Question: Any relationship between bed-wetting and PD?
Answer: She's not personally aware of this. This is worth looking in to. Most people focus on what happens in adulthood because PD is related to age. This is a mistake because there's overlap between neuro-development and neuro-degeneration.

Question: Any relationship between PD and essential tremor?
Answer: She believes there's a gene out there to be discovered that accounts for both PD and ET.

Question: Any relationship between epilepsy and PD?
Answer: She hasn't seen this. She has seen a relationship between "brain stem fits or fainting spells" and those with PD.

Question: Any relationship between stiffness, spasticity, and difficulties walking and PD?
Answer: There are families that have this prior to PD.

Question: If my husband has PD, I have RLS, are our children at greater risk of getting PD?
Answer: Usually two risk factors coming together are not additive. 4-9% increased risk. Don't lose sleep over this!

Question: What is the difference between PD and Parkinsonism?
Answer: Parkinsonism is an umbrella term. PD is underneath that umbrella term. Those with PD have Lewy bodies and loss of neurons in the substantia nigra. The brains of those with parkinsonism don't have these same findings. Those with parkinsonism don't respond well to dopamine-replacement strategies.

Question: Do you see PD and LBD as two separate diseases or two ends of a spectrum?
Answer: I see these as two ends of a spectrum called synucleinopathies. There is a big dispute about this.

Question: Define "exercise."
Answer: What's the best exercise? The best exercise is the one that you will do regularly every day for 30 minutes or more. She likes the combination of walking, stretching, and vigorous activity.



Some notes from:
Recent and Future Innovation in the Treatment of Parkinson’s Disease
Mark Stacy, M.D., Duke University Medical Center

Drugs that sound too good to be true probably are.

When dealing with a PD diagnosis, patients go through Kubler-Ross's five stages of grief -- denial, anger, mourning, bargaining, and acceptance.

PD probably won't change your life as much as you think it will.

FDA approval process:
Preclinical stage: test population are laboratory and animals; purpose is to assess safety and biological activity
Phase I: test population is 20-80 healthy human subjects; purpose is to determine safety and dose range
Phase II: test population is 100-300 PD subjects; purpose is to evaluate efficacy and establish safety; proof of principle
Phase III: test population is 1000-3000 PD subjects; purpose is to demonstrate efficacy and long-term safety
File NDA at FDA for approval to market drug
Phase IV: post-approval studies; purpose is to expand indication; "FDA request"; this is where a drug has already been approved for one indication but a request is made to also approve the drug for an additional indication; a phase II trial occurs for the new indication

In a 1992 study of 100 patients clinically diagnosed with PD, upon autopsy it was revealed that 76 had cortical and nigral Lewy bodies, and 24 had no Lewy bodies (diagnoses included PSP, MSA, AD, etc). [Hughes AJ, et al. Accuracy of clinical diagnosis of idiopathic Parkinson's disease... JNNP March 1992, 55 (3), 181-4.]

Grosset discovered that 10% of PD patients were misdiagnosed.

We need to correctly diagnose PD clinically because we want to only admit PD patients to PD drug trials! What if because of errors in clinical diagnosis we've missed seeing the efficacy of certain medications?

If you have two of the cardinal symptoms of PD -- rest tremor, bradykinesia (slow movement), and rigidity -- then you have a 70% chance of having PD. If the MD puts you on anti-parkinsonism therapy and you have a brisk response, you have a 90% chance of having PD. They can do better than this in the UK with DaTSCAN of dopamine in the brain. (Stacy hopes we can get the DaTSCAN in the US soon to take better care of patients and to enroll only PD patients in drug trials.) A study by Ken Marek shows that MDs are very good at making a correct diagnosis (ie, finding patients with a dopaminergic deficit) 23 months after the initial diagnosis of PD.

SPECT imaging is important but it is not approved for use in the US. It's already being used in other countries.

We have five dopamine receptors in our brains. There are two classes: the D2 family (D2, D3, D4) and the D1 family (D1, D5). In treating PD, we want to effect the D2 and D1 receptors; this is where the faulty motor program is. If a patient starts having psychosis, that is probably from the D4 or D1 receptor. If we give you too much dopamine that is not specific to receptors, we can give you hallucinations and we can improve your motor skills. The patient wants to move and doesn't care about the hallucinations. The caregivers doesn't want the hallucinations and doesn't care about the movement. A drug that doesn't allow the D4 or D1 receptor to be touched might be a compromise.

See the slide from Schapira and Olanow, JAMA 2004, 291:358-364. Drugs dealing with:
Oxidative stress: antioxidants (eg, creatine) and MAO-B inhibitors (eg, selegiline, rasagiline)
Mitochondrial dysfunction: CoQ10
Excitotoxicity: antiglutamatergic agents (eg, riluzole, Namenda) and calcium channel blockers (eg, isradipine)
Inflammation
Protein handling dysfunction with Lewy body formation: proteosomal enhancers (eg, LNK-754) and heat shock proteins
Neuronal dysfunction: trophic factors (eg, GDNF, GPI-1485)
Apoptosis: antiapoptic agents (eg, Pramipexole, Ropinirole, Minocycline, CEP-1437, TCH-346)

Isradipine is approved for high blood pressure (hypertension) treatment and may have a role in slowing the progression of PD.

LNK-754 is an exciting compound (pill). It may alter the ubiquitinization of alpha-synuclein. It has been approved for cancer therapy.

We haven't figured out a good delivery system for GDNF. It's supposed to grow the cells that are dying from PD.

GPI-1485 did not make efficacy. Development was halted on this pill in 2006.

CoQ10 is a phase IV agent being studied by the NIH in the NET-PD study. 1200mg/day - slight benefit in patients with early PD in 16-month trial. Lower doses did nothing. 1200mg/day costs about $300/month. A new trial will compare 1200mg to 2400mg/day in 600 subjects from 60 North American sites. If there is efficacy, the FDA will have to move this from a nutritional supplement to a medication so that insurance companies will pay for it.

(Around 30:00, more is said about isradipine.)

Urate (uric acid) is an antioxidant and early predictor of PD risk and progression. The higher the urate level the slower the progression. Gout is a known side effect of high urate.

In NET-PD study, 12 drugs are in clinical trials.

Creatine effects mitochondrial energy production.

Minocycline is an antibiotic with anti-inflammatory properties. Animal studies in PD and ALS models show evidence of neuroprotection. Inhibition of glial activation. Inhibits apoptosis.

One study looked at creatine, minocycline, and placebo. (Around 35:00 more is said about this.)

It is easy to join a creatine study.

Sinemet was approved in 1975.

In treating PD, decisions should be made about whether medications are beneficial to the patient every 3 months because it takes that long for the brain to show any change.

Two gene therapy treatments are being studied: Ceregene (phase III; very exciting) and Neurologix (phase II).

Cell transplant treatments being studied include: human fetal (phase III), spheramine (phase II; Titan), porcine (phase II; halted), and stem cells (pre-clinical stage).

PD meds treat and cure high blood pressure.

Impulse control disorders are common in PD. The one no one talks about is hyper-sexuality. This needs to be mentioned to your MD if you have this! Some of the meds cause impulse dyscontrol.

Un-met needs for medications: dyskinesia, psychosis.

Acadia ACP-103 is a drug for psychosis that will be studied soon.


Question: Is creatine available?
Answer: It is available at GNC Nutrition. Check with your MD before you take this medication. We aren't sure about dosing.

Question: What about glutathione?
Answer: There is no evidence that glutathione gets to the brain. Drugs need to be studied through the FDA process. MDs should give patients hope but not false hope. He's not saying that if you are taking glutathione you should stop.

Question: How do we find out about trials?
Answer: Go to pdtrials.org.

Question: We are new to this. What do we say to our neurologist?
Answer: You need to have a doctor you can talk with in terms of your Parkinson's treatment. A doctor you can trust. When I first see a patient, I tell them that just about anything we do in the first five years will work fine. After that, it's not how good you are, it's not how good I am, it's something in between. So you have about 5 years to fine someone you can develop something in between, where you can have a dialogue where you can discuss the symptoms. If you come to see a doctor, I would ask you to come armed. List the 30 things that are bothering you and ask me to tell you what I can help you with. I may say "I can't help you with that one" and you move on to the next item. Listing all the things that bother you defines an appropriate place for an MD to speak with you about your symptoms. And that's your responsibility. I would urge you all to be modern consumers of healthcare and use me as your consultant that you have problems that you want to get help with.

Question: Are you starting all of your patients on something now (such as rasagiline)?
Answer: I'm more likely to see patients with motor disability when I first see them. Drugs to treat motor disability are dopamine agonists and levodopa. If I have a patient who doesn't have motor disability - say they just have a tremor but it doesn't really bother them - that's the place when I've changed my mind. I used to say "that's OK." Now I at least present the TEMPO data (where there was a delayed start and it showed that there was a difference at a year if you started earlier).

Question: What data is there on Requip to treat PD?
Answer: Requip is similar to Mirapex. They both went through the normal FDA pathway. Both are highly effective agents in the long-term. Side effects for both are low blood pressure, sometimes confusion, sometimes nausea.

Question: How can patients get better quality of life?
Answer: The FDA is interested in this. We have not designed a scale that captures benefit in quality of life in a 3-month or 6-month trial. The father of PD in this country is Dr. Stanley Fahn, adviser to PDF. He talked a long time ago about doing quality of life scales in his clinic. Patients newly diagnosed with PD reported a low quality of life. Patients who had PD for longer reached the point of acceptance and had a better quality of life, despite greater disability. So, quality of life is very difficult to measure. And it's not just a function of PD.

Question: What drugs can help with balance and light-headedness?
Answer: PD affects balance and there's not a lot we can do for that from a motor standpoint. Loss of balance can occur for a lot of reasons. You can freeze and then tumble over. You can have dyskinesia and then fall. You can stand up, your BP drops, and you can pass out and fall. Take your BP sitting and standing. I caution all of you: a cardiologist or internist should never treat a SITTING blood pressure. You don't care about sitting; you care about walking! A doctor should always treat a standing blood pressure. If a doctor takes your BP sitting, tell them also to take it standing. I care if your standing BP is less than 100/50. I want you to take as much salt as you can stand to raise your BP; when your feet start to swell, then you can back off the salt. Two agents you can take are midodrine and Florinef.

Question: Why are SPECT scans not available in the US?
Answer: Because of corporate changes. GE bought Amersham (sp?). Amersham wanted to bring another type of SPECT agent to market. It's been found that the drug that GE started to bring to market in Europe is easier to use. So it got slowed down bringing this agent to the US. GE is talking to the FDA about using European trial data.

Question: Is punding an issue with a dopamine agonist or levodopa.
Answer: Punding -- which is doing the same thing over and over -- is more tightly linked to levodopa but people on dopamine agonists can also have this problem. DAs are more tightly linked to hypersexuality, gambling, binge eating.

Question: What's the criteria for DBS?
Answer: When I believe I've reached the point when I can no longer manage you with medications alone then I start talking about DBS (deep brain stimulation). Quality of life is the issue. DBS is good if there's lots of weight loss or if there's lots of dyskinesia.



Some notes from:
Stem Cells and Gene Therapy for Parkinson’s Disease: Is the Cure on the Horizon?
Clive Svendsen, Ph.D., University of Wisconsin, Madison

He likes this website: determined2heal.org.

There are 100 billion cells in the brain! There are 250 different types of cells in the body. A neuron is a unit in the brain that communicates.

There are two important support cells to know about -- oligodendrocytes and astrocytes. An oligodendrocyte puts myelin around your nerve connections. (In MS, myelin is disrupted.) Myelin is like insulation. An astrocyte is a nursing cell. It sits next to the dopamine neuron and feeds it. The astrocyte is like a hospital.

There's a good picture of the brain at 8:32.

Dopamine isn't released where the neuron is. The dopamine is released at the end of the wire. Dopamine is like oil in a car. Why do they die? I think: predisposition in combination with environmental toxin. L-dopa is replacing the oil. Something has to release the dopamine in the system and that's a dopamine neuron. Too little dopamine and there's freezing. Too much dopamine and there are dyskinesias.

Adult brain transplants don't work! But we can take fetal tissue and transplant it into an adult brain. Function in these treated rats is restored. This was first done in rats in 1987 in Sweden.

350 patients have received fetal tissue transplants worldwide. Many patients are doing very well. For 14 years these fetal cells can survive and produce dopamine. But this doesn't cure PD.

Why isn't everyone doing this? Here's the catch: the fetal cells are put into the striatum, where the dopamine neurons are projected. They don't put the cells back in the base of the brain where the neurons die. These cells don't regenerate very well; they won't make a new connection in the adult brain all the way up.

Some patients have abnormal movements associated with the transplants. These can't be turned off.

These two scientific challenges are why fetal tissue transplants have basically stopped worldwide. Stem cells may be the answer.

All tissue has stem cells in them.

Embryonic stem cells and fetal stem cells are the only two that can make dopamine neurons sufficiently. Other stem cell types in adults can't make dopamine. And the embryonic stem cell is the most efficient maker of dopamine neurons.

We turn the stem cells into neurons, oligodendroctyes, and astrocytes. With dopamine neurons, we still have the problem of making a connection.

Right now there are no clinical trial for stem cells for dopamine neuron replacement.

Astrocytes sit between the blood vessels of the brain and the dopamine neurons. Astrocytes control the blood brain barrier. (Astrocytes are types of cells.) In ALS, the astrocyte is sick before the motor neuron. Maybe the same thing is true in PD.

We are far away from a cure for PD. Stem cells are a possible treatment for PD -- modulating PD, controlling the symptoms.

GDNF (glial cell line derived neurotrophic factor) is a molecule. GDNF can protect dopamine neurons in the brain. GDNF can't penetrate the brain tissue. How can we get this drug into the brain? Amgen (which holds the patent on GDNF) did a small clinical trial several years ago; negative results.

In a study he and Gill did in 1999 in Bristol, GDNF was infused directly into the brain. You can get GDNF into the substantia nigra by getting it into the striatum. Open label trial. Paper published in 2003. (Addendum published in 2006.) Solid effect and very safe. Patients got more dopamine in the brain. Be careful - there could be a placebo effect.

GrassRoots did a whole website on another GDNF trial in the US. The two groups were not significantly different.

Movement Disorders journal, Feb '06 article on GDNF therapy at a crossroads.

We still haven't done the correct trial of GDNF. Amgen has pulled GDNF completely; it's not available.

He would like to do in vivo gene therapy using viral particles to introduce GDNF. A similar compound to GDNF is Neurturin (CERE-120), produced by Ceregene. There are three gene therapy clinical trials going on now, including Neurturin.

The problem: there is no way to regulate gene dosage after therapy starts in any of these three trials.

What if we can make stem cells in the dish produce astrocytes which can be used to deliver GDNF and introduce this ex vivo? He's done studies in rats and now monkeys. He calls this a "combined approach."

Do we need embryos to get pluripotent stem cells? Two important papers were published recently on this. In one study, skin cells were the starting point. They turned into iPS cells.

We need to think about stem cell therapy differently with each disease. Some diseases (such as ALS) are more serious than PD. In PD, lower risk treatments are preferable to high risk treatments like stem cell therapy.


Question: What kind of experiments are you doing with astrocytes?
Answer: We are comparing the effect of GDNF release or astrocyte release. One of the problems with animal models (monkeys and rats) in PD is that PD has to be introduced acutely with a toxin injection. PD is a slow, long disease. Good genetic models aren't forthcoming yet.

Question: What about using eye cells?
Answer: There is one clinical trial going on now with retinal epithelial cells. These eye cells make some dopamine. This is a blinded trial. Titan is the company. The safety part of the study was successful. Adult eye cells are used.

Question: What was the problem with Amgen and the reluctance to continue the GDNF trials?
Answer: They considered their trials to be unsuccessful. And there seemed to be the chance of toxicity.

Question: What are the risks of tumors developing with stem cell transplants?
Answer: This is dependent on what type of stem cells you use. We want to reduce the risk of teratomas in the brain. Fetal stem cells don't form tumors.

Question: How far away are we from clinical trials for stem cell GDNF treatment for PD?
Answer: We are looking for a way to regulate the GDNF release before we proceed with a clinical trial. Others may proceed with a clinical trial without worrying about the regulation of GDNF.

Question: Is there a patent on iPS cells?
Answer: It's a complete mess at the moment. Many patents have been filed. There's no clarity if anyone will own the patents.

Question: Is there any hope for fat cells?
Answer: We don't know what cells are best to make pluripotent cells. Great if you could go in for a liposuction and get a stem cell line at the same time. This is a business opportunity!



Some notes from:
Final Q&A (with all three speakers and Robin Elliott, executive director of PDF, as the moderator)

Question: Is there any connection between PD and ADD?
Answer by Stacy: There is a relationship. We way overdose ADD in this country. We have to be careful not to overdose PD.

Question: Is pallidotomy still being used?
Answer by Gwinn: Pallidotomy has been largely replaced by DBS in most centers.
Answer by Stacy: DBS occurs in the subthalamic nucleus. DBS is more nuanced.

Question: What is the connection between PD and Lewy Body Disease? Can LBD be diagnosed while someone is alive?
Answer by Gwinn: These are both clinical diagnoses. There's not a test you can take. There may be imaging studies you can have but these are not commonly available. The diagnosis is based on clinical criteria. If the parkinsonism precedes the problems with thinking chronologically, it's called PD. If dementia comes later, it is called Parkinson's Disease Dementia. If dementia comes first, it's called Lewy Body Dementia or Lewy Body Disease. We talked earlier about whether this is a spectrum of disorders or two different disorders. I believe it's a spectrum, despite the fact that the symptoms can be very different.

Question: What, if anything, is in the works for the advanced PD patient?
Answer by Stacy: Non-motor symptoms, dyskinesia, dementia, and psychosis are all un-met needs. These things are in the works for advanced PD. MDs always use our best guns first. Patients think MDs are holding medications in reserve.

Answer by Svendsen: Advanced patients don't respond well to dopamine. There aren't many treatments available to those who don't respond well to dopamine. Stem cells are probably not the answer for the end-stages.

Answer by Gwinn: People don't die OF PD; they die WITH PD. Life-threatening things in PD are pneumonia and falling and hitting your head. It's important to use a walker if needed and get exercise. (10:42) The lung runs from the neck down to the bottom of the rib cage. In PD, when people are hunched over, the lung is only expanding so much. That creates empty spaces in your lungs (in two places), where infection can arise. So it's very important to do stretches, even signing in the shower is highly therapeutic for almost all involved. Simple things to keep your lungs expanded, like lying on your back, stretching your arms in one direction, and stretching your legs in another direction -- these aren't fancy things but they are things you can do to help you and might even save your life.

Question: If some of these techniques by Dr. Svendsen were perfected and safe, would you consider this early in someone's PD or would you wait until later?
Answer by Stacy: I would want to do some safety studies in moderately advanced patients. I would wait for someone with postural instability. So when we pull on your shoulders, you don't keep your balance easily and we have to catch you. So that's stage 3. And you are having motor fluctuations and dyskinesias -- so we know you are having a levodopa response. If you don't respond to levodopa any more, there's not a lot to do. (13:14) I would do safety studies in that population. But this is a regenerative trial and I would want my PD patients to receive that drug as early as possible. I would first take the moderately advanced patient, and then work my way down to the medium patient, and then I would eventually consider the low risk patient. The interesting thing about using supporter cells rather than neuronal tissue... It seems to be that the oil analogy works. Neuronal tissue has more chances of physiological impact and more potential to grow in different directions and not provide a supportive, moderating effect of neuronal activity.

Answer by Gwinn: None of the therapies discussed together are going to be single-bullet therapies. They will all have to be used in combination. Think about diabetes; there are different types of insulin treatment over time. We just don't know what will work.

Answer by Stacy: There are some patients who really do well with selegiline. It blocks MAO-B. MAO-B is more in glial tissue than in neurons. Are we thinking about astrocytes?

Answer by Svendsen: It's tough to get across that neurons aren't important. It's hard to convince neurobiologists that astrocytes are important. (16:10) There's this whole thing with the neuron being king. The astrocytes can possibly modulate. There's great work coming out of Stanford now (Ben Barrizer's? group) and Rochester (Mike Niedergard -sp?) showing that astrocytes can go around synapses and modulate synaptic transmission directly. If we can modulate the synapse we can make dopamine work more efficiently. This is a really important new angle that drug companies can work at. I'm a proponent of using the astrocyte as a new tool.

Question: What positive things are going on in other countries?
Answer by Svendsen: (17:23) There's a lot of medical tourism going on where you can go to anywhere in the world and get a stem cell transplant. This is truer for diseases of the heart. There is some evidence that adult bone marrow stem cells can be transplanted and can have some effect on heart attack. It's not been proven as effective in this country. However, you can spend $30K and go to Bangkok for this same therapy. You have to be careful. Stem cell companies say they can cure whatever you have; it doesn't matter what it is. 95% of these places are charlatans. Do not go there! The only thing these places have in common is that they cost $30K.

Answer by Gwinn: This is a wallet biopsy.

Answer by Svendsen: On the research front, the community is pretty global now. I don't see anyone in the stem cell field rushing away with the lead. Britain has some interesting rules. California has released $3 billion in stem cell research. Just yesterday they released $370 million for buildings devoted to this type of research. It's the wild west because there are no laws in this country. If you grow an embryo more than 14 days in London, you can get in trouble.

Answer by Stacy: A researcher has a basic research lab at Duke. He does basic safety testing in Brazil. He has a lab in Sweden. There are advantages in all these places. (This person is not directly in the medical field.)

Answer by Robin Elliott (Executive Director of PDF): 70 cents of every dollar in basic medical research spent worldwide is still spent in the US. NIH alone is a $30 billion operation. As global as the system is, the center of gravity is very much here. Sweden is very important. Israel has a big investment in stem cell research. And Japan is very important.

Question: There's a book called "The Wisdom of the Crowd." Today's a good example of that. What are the roadblocks for those who have PD to bring together drug companies who are after the bottom line, government bureaucracy, etc -- all of these things that are roadblocks to moving forward? How can the public overcome these roadblocks?
Answer by Robin Elliott: There's a crisis in the US on medical research funding. There has been a real decline in money going to the NIH in the last 3 years. This wreaks havoc in science. It means that many young scientists can't get their grants. In Clive's field, for every 100 applications to NIH, only 8% get funded. There are going to be several lean years ahead.

Answer by Gwinn: I've seen improvements in our attitudes about public and private partnerships. NIH has matured in terms of how to build those relationships. We can still do these better. Lots of trial data never becomes available. How to make this data available to academic communities?

Answer by Stacy: I'm not a researcher. The public's responsibility is to give clinicians the courage to find a cure. The public should tell researchers to share data. The public needs to give clinicians and researchers the courage to overcome false barriers.


----------------------------
Date: Mon, 19 May 2008 17:09:40 -0700
To: rriddle@stanfordalumni.org
From: Robin Riddle <rriddle@stanfordalumni.org>
Subject: "What's In The PD Pipeline?" - Online Webcast Available

Apparently I'm way behind in my email! I've just come across an announcement that the Parkinson's Disease Foundation (PDF) is hosting a series of symposia that will be webcast around the US, starting with the seminar on 5/9/08 addressing "What's In The PD Pipeline?" The presentations were on these topics: genetic lessons, recent and future innovation in PD treatment, stem cells, and gene therapy. Though the focus was on PD, I assume most of what was said applies to the atypical parkinsonism world as well. Apparently this symposium was excellent. And fortunately the webcast is now available on the PDF website.

The agenda for the 5/9 symposium was:

Friday, May 9, 2008

10:00 AM ­ 10:50 AM
Genetic Lessons and New Approaches in Learning about Parkinson’s Diseases
Katrina Gwinn, M.D., NIH/NINDS

11:10 AM ­ 12:00 PM
Recent and Future Innovation in the Treatment of Parkinson’s Disease
Mark Stacy, M.D., Duke University Medical Center

1:15 PM ­ 2:05 PM
Stem Cells and Gene Therapy for Parkinson’s Disease: Is the Cure on the Horizon?
Clive Svendsen, Ph.D., University of Wisconsin, Madison

2:20 PM ­ 3:00 PM
Open Questions / Closing

Click here to start the process:
http://event.netbriefings.com/event/pdf ... dpipeline/

(If that doesn't work, click here -- http://www.pdf.org/webcast/charlotte.cfm -- and scroll down and click on "View webcast of this symposium.")

You'll have to register (name, city/state/country, how you heard about this, and your affiliation); access to the webcast archive is free.


Tue Jun 10, 2008 1:55 am
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