How do you TRAP a Disease?

There is some new and exciting research out in the media over the past few days. It seems that some smart scientists have discovered a way to identify the genetic messages of distinct cells.

Before I go into how this works I want to discuss how this helps Parkinson's Disease research. As is well known, the ongoing, progressive cause of Parkinson's is the death of dopamine neurons in the substantia nigra section of the brain. The aspect of this that is not well known is that there are 2 different types of dopamine neurons in this brain section, but only one of the types dies off in PD. No one understands why this is the case, how it happens or if there is a way to stop it. The main reason that none of this process is understood is that there has been no good way to isolate and analyze these two different cell types. That is there wasn't a way until recently.

Scientists at the Michael Stern Parkinson's Disease Foundation, part of Rockefeller University, have developed a method to distinguish between these 2 types of dopamine cells as well as all other cell types. They developed a procedure called Translational Ribosome Affinity Purification (TRAP) that can essentially isolate the genetic messages of any cell thereby showing the differences in the cells at a genetic level.

All cells have a structure called ribosomes that work as the protein production factories. The proteins that are "created" within the ribosomes are a direct result of their genetic make up. By looking at which proteins are produced scientists can determine which genes are "turned on" in the cell. By understanding which genes are "turned on" scientists can determine differences in similar cell types.

TRAP uses genetically engineered mice to tag ribosomes in a particular cell type and then capture the genetic messages as they pass through ribosomes on their way to creating proteins.

So how does this research help Parkinson's Disease? Well, first it allows for better research into how the two types of dopamine neurons differ. Understanding this difference may point to reasons why one type dies while the other lives on as usual. Also, understanding the proteins created by the diseased cell type may offer insight into better treatments for PD. Who knows... it may be possible to somehow supplement the proteins that the dying cells created.

All in all I think this is a remarkable breakthrough that has the potential to speed up research into new treatments as well as new avenues for research into what causes Parkinson's Disease in the first place.

Parkinson's and Sleep Disorders

Sleep disorders or disturbances are one of the many symptoms reported by Parkinson's patients that do not tend to be as widely discussed. Several researchers have suggested that the sleep disturbances may pre-date the more obvious motor symptoms by several years.

The sleep disturbances in PD intrigue me because it is widely reported that any tremors stop while PD patients are sleeping. At the same time researchers note that PD patients seem to lose the normal function of "muscles freezing" while sleeping. Unlike "normal" people PD patients maintain more control over their muscles which can cause issues with "acting out" their dreams. This ability can cause PD patients to kick, hit, walk, talk, etc. regularly while asleep. To me the tremors stopping, but general movements increasing seems very odd, to say the least.

Because of this seemingly in congruent situation I decided to research more about sleep disorders in PD. What I found is that researchers believe the decrease in dopamine directly affects sleep. It has been shown in studies with mice that decreasing dopamine caused the mice to experience significant difficulties with sleeping. The mice also exhibited less brain activity associated with dreaming. Conversely if mice were given increased dopamine they were able to sleep and exhibited increased brain activity associated with dreaming during wakefulness. It is also reported that dopamine agonists tend to have excessive daytime sleepiness as a side effect. Given the studies in mice showing that increased dopamine can cause sleepiness this side effect makes sense.

Exactly how to treat the sleep disturbances does not have a clear cut answer. (At least not one that I have found.) The fact that depression and dementia can also be associated with PD complicates the issue of sleep disorders as both of these conditions can affect sleep on their own.

The most interesting aspect of what I learned about PD and sleep disturbances is still the idea that the motor symptoms are probably pre-dated by sleep disturbances. Wouldn't it be great to be able to diagnose sleep disturbances specific to PD early on so that the patient could start some of the medications that may delay onset of this disease?

Please let me know if you found this information useful or if there is something else you'd like to know about. I'll research any aspect of PD and blog about it to let you know what I find.

Is Parkinson's Disease Inherited?

Is Parkinson's Disease Inherited? That was the question I asked back in 1993 to one of my neurobiology professors, a Parkinson's expert and researcher. On that day he told me definitively, "No." Even back then, 15 years ago, I suspected he was wrong. I really thought that there was probably some sort of genetic connection that was not understood at all.

Today scientists believe that there is a genetic connection, in fact, they have identified several mutations that can give rise to Parkinson's Disease. That being said, scientists estimate that less than 25% of all PD cases are genetically linked and they also believe that not all those with the gene mutations develop PD.

The information about familial (genetic) Parkinson's is actually quite extensive now. (Isn't it amazing what we have learned in 15 years?) Now scientists have numerous genetic suspects. Here is a summary of some of the most prevalent.

1. LRRK2 (leucine-rich repeat kinase)- This gene is a dominant gene, meaning that a person only needs one copy of this gene in order for it to be expressed in an individual. Scientists have identified at least 20 mutations in families that exhibit late onset PD. This genetic "flaw" is the most common form of Parkinson's as far as scientists know at this time. This is the genetic mutation that Sergey Brin identified in his gene make up.

2. GIGYF2- Mutations on this gene are known to cause a single amino acid substitution in the protein this gene encodes for. What does this mean? Essentially one link in the chain of a protein is swapped out for a different kind of link which then leads to the protein being formed incorrectly. The interesting aspect of this genetic mutation is that it is also assoicated wiht Insulin production. Scientists aren't sure, but they think there might be a connection between PD and Insulin and thereby possibly diabetes. There are now ongoing studies to try to piece together how these diseases are inter-related, if at all.

3. A study of a handful of French families with Parkinson's uncovered that duplications in the gene that creates the alpha-synuclein protein may cause PD. It is known that alpha-synuclein protein is a major component of Lewy Bodies, an abnormal "clump" of proteins that form inside nerve cells. The French study showed that a duplication of this gene caused PD similar to other types of PD, but that a triplication of the same gene caused a devastating form of PD with an average onset of 34 and a rapid decline into dementia. I know from reading other articles in the past that there is a big push to look into whether or not limiting or removing "extra" alpha-synuclein could slow the progression of PD.

4. LI66P mutation- This particular mutation is linked to an early onset form of familial PD. It is thought that this mutation disrupts DJ-1 protein folding. By disrupting folding of a protein this mutation would essentially render the DJ-1 protein useless and upset the functions that it performs in the body. LI66P is recessive so someone would have to receive the same gene mutation from both parents in order to have its affects exhibit.

There are several other genetic mutations that are linked to PD, but I think 4 is enough for any one blog posting. Just because someone has one of these mutations does not appear to be enough to develop Parkinson's Disease. It is thought that the genetic mutations, at least for the most part, make someone more susceptible, but that some sort of environmental trigger needs to occur as well for a person to develop the disease. The exact mechanisms are not known.

So I now have a question- if PD ran in your family would you want to know if you had any of these genetic factors if there was nothing to do to prevent the disease? PD does run in my family, my Mom, my Grandpa, but as of now I have no desire to have any genetic tests done. That may change in the future especially if preventative methods are developed. Only time will tell.

Stem Cells and Parkinson's Disease

Stem cells have long been in the news as a potential therapy or possible cure for Parkinson's Disease. So what exactly are stem cells? First you should know that there are several different types of stem cells. The two types that are mentioned most often are embryonic stem cells and adult stem cells. There are other types, but let's stick to these two.

A stem cell is a cell that has three basic properties:

1. It can "renew" or regenerate itself for a much longer period of time than regular cells in the body,

2. It is unspecialized- meaning that it has not "chosen" a specific tissue type, i.e.- heart muscle, brain tissue, liver cell,

3. It has the ability to specialize- meaning it can become a specific type of tissue and take on that tissue's role in the body.

An embryonic stem cell is an undifferentiated (unspecified) cell from a 5-day old pre-implementation embryo.

An adult stem cell (aka somatic cell) is also an undifferentiated cell but these cells come from many types of tissue, bone marrow, brain tissue, etc. There is no embryo involved in these types of cells.

So what's all the debate about? Well, during the extraction of embryonic stem cells the embryo itself is generally destroyed. This risk raises the ehtical/moral questions about whether or not the procedure is destroying life or advancing science. Adult stem cells can also be used for research and possibly therapies, but it is not well known if adult stem cells can differentiate into all the cell types in the body. Embryonic stem cells are more versatile in that they can become most, if not all, types of cells in the body. However, adult stem cells are not rejected after implantation as they are from the patient's body already.

Until recently it seemed like both embryonic and adult stem cells both had advantages and that the moral and political debate would continue for years. Then something amazing happened back in November 2007, two scientists working separately were able to turn ordinary human skin cells into what could effectively be considered embryonic stem cells. The scientists took regular human skin cells and with the help of some genetically engineered viruses were able to transform the skin cells into embryo-like stem cells. Their method used four genes in a proper sequence to make the skin cells almost indistinguishable from embryonic stem cells.

This new finding breaks open the entire stem cell research world. Now there is a way to take regular cells, without hurting anyone or anything, and turn it into essentially embryonic stem cells. With any luck this method will allow for vastly increased ways to study embryonic stem cell, develop new therapies using them and also increase federal funding for these lines of research.

I will of course be watching for further developments in this research as it holds out hope for a cure or at least better therapies for Parkinson's Disease. When I find further research in this area believe me that it will be posted.

Parkinson's Disease Caregivers

Today I am going to write about caregivers of people with Parkinson's. As usual when I decided this was the topic I wanted to write about I did some research on the Internet to see what sites and information already exists in the ethernet. To my surprise there was remarkably little information and only a couple of sites that seemed to focus on the caregiver at all. Now, I think that is something that I will have to work to change in the future. Obviously I will not change that in one blog posting so I will not try.

The one site I came across that seemed to have a lot of information and a good forum for caregivers and/or patients to share information is:

www.myparkinsons.org

This site has some useful information for caregivers, links to MANY other parkinson's sites, but what seemed the most useful in my mind was the forum. There were numerous postings and it definitely appears that the site has a true community that will try to answer questions that you have.

I personally think that caring for someone who has PD must be very difficult, especially as the patient's health begins to decline. My Mom has PD and my Dad is the primary caregiver so I do not know exactly how tough it is, but I am sure it is not easy.

In general the caregiver information out there all seems to say the same thing: get informed, stay informed, and make sure to take some time for yourself as well. I think that is all good advice.

To all the caregivers I wish you luck and salute you for your fight against Parkinson's Disease in whatever way you do it.

Parkinson’s Disease and Sonic Hedgehog

You read the title of this post correctly! Now you’re asking what the heck do Parkinson’s Disease and Sonic the Hodgehog have in common? Well, the disease and the video game have nothing in common, but a brain protein named after the video game is being linked to the disease. That’s right there is a protein in your brain named Sonic Hedgehog (shh) that is implicated in Parkinson’s Disease. I thought I was reading something wrong when I first read an article about Sonic Hedgehog, but I was not wrong and this was no joke.

There are a group of brain proteins called hedgehogs of which Sonic Hedgehog is one. The role of shh is seen during embryogenesis (embryo growth) and spurs development of dopaminergic neurons in the basal ganglia section of the brain which is affected in PD. The protein is now known to exist in the adult brain too.

The name alone inspired me to learn more about this protein so I began searching the Internet for different articles about this uniquely named molecule. What I found was an entire body of knowledge and study about this “hedgehog” protein. It turns out that there are three separate avenues of study of shh in Parkinson’s.

First, researchers are looking at whether this protein could cause adult stem cells in the brain to differentiate into (become) dopamine producing neurons. Obviously being able to grow more dopaminergic neurons in the affected areas in patients with PD would help tremendously. Researchers are still working on this avenue of study in animals. Time will tell if this has efficacy in humans.

The second avenue of research explores applying shh directly into the basal ganglia. It appears that shh can work as an actual neurotransmitter in the brain and when applied to the basal ganglia in animal studies the amount of electrical activity in the subthalamic nucleus decreased. Since the subthalamic nucleus is hyperactive in PD, a compound that decreases this activity would be a possible treatment. Again, this line of research is being pursued, but human results are not known at this time.

Lastly, several researchers explored the neuroprotective properties of Sonic Hedgehog and also another protein, Gli-1. They delivered both of these compounds to the brain via a genetically engineered virus. What they found was that both of these proteins appear to protect neurons and prevent neuronal loss as compared to other controls. Sonic saves the day!

I started reading about Sonic Hedgehog because I found the name amusing and thought it was great that neuroscientists have a wonderful sense of humor. What I found was 3 different paths of research about this one compound. I am still amazed that researchers can take one particular protein and then can find 3 completely different potential ways that this protein can help in a disease like Parkinson’s. None of these avenues have led to clinical applications yet, but that does not mean that one or all won’t in the future.

Pain and Parkinson's Disease

A new research study conducted in Italy is making the news today. The study looked at the incidence of pain reported by Parkinson’s patients versus a normal control group. I found this study interesting because it shows that researchers are recognizing that there are symptoms besides motor symptoms that may lead to quality of life issues or may help diagnose the disease easier. In my opinion this study is not a huge breakthrough in that it is not a bug leap closer to a cure, but all new knowledge does help move us collectively closer to the goal of a cure.

The researchers started the study with the hypothesis that pain is associated with Parkinson’s at clinical onset or at some point thereafter. The study divided pain into 2 categories: dystonic and non-dystonic pain. The first type, dystonic, is characterized as painful sensations, often described as cramping or arthritis and is caused by involuntary muscle contractions. Non-dystonic pain is essentially pain with the absence of dystonic pain. What the researchers found was that pain associated with dystonia was statistically higher in PD patients versus the control group. (69.9% vs 62.8%, p=0.04) The researchers also found that non-dystonic pain was not statistically higher for Parkinson’s patients, but the occurrence of non-dystonic pain was correlated to the onset of clinical Parkinson’s.

All of this information is overall interesting even if I don’t see a direct application to immediate better treatments or a cure. To me what this means is that doctors should pay attention to unexplained, dystonic pain and keep Parkinson’s as a possible diagnosis in the back of their minds. I have a feeling that many people with Young Onset Parkinson’s that present with pain as one of their main symptoms will have many tests to rule out a host of other possible causes before a PD diagnosis is made. I have no doubt that going through all the tests must be aggravating to say the least.

To read the abstract of this study from the Archives of Neurology click this link.

http://archneur.ama-assn.org/cgi/content/short/65/9/1191

Depression in Parkinson's Disease

The link between Parkinson's Disease and depression has come to light more in the past 5 years or so. Researchers are finally beginning to notice that depression occurs in a large part of the PD population (estimates are 40-50%).

The exact reasons for why such a large portion of Parkinson's patients develop depression are not entirely known. It is thought that the biochemical alterations are a large culprit, but stess and psycho-social reasons probably play a role too. I am sure that people on hearing their diagnosis of PD are less than happy and may experience some level of depression for a while, but when does this depression cross the line from feeling down about a difficult disease into a clinical depression? Also, there is evidence that 12-37% of patients with depressive symptoms develop these symptoms prior to developing motor symptoms. Does this mean that the depression is mostly biochemical? I do not know.

How do you piece apart the chemical changes in a person's brain from the psycho-social or stress induced changes in someone's attitude or behavior? This is a question that I think will take years to answer, if it is able to be answered at all.

Since there is a large population of depression in PD you would think that treatments would be fairly well understood. That is not true at all and actually the opposite is closer to the truth. From the research I have read there are several anti-depressants that are possible for treatment, but none of them have significant research surrounding their use and efficacy in treating depression in Parkinson's. That being said, an anti-depressant may be the right choice for many patients. A motor disease specialist should be able to recommend some medications as possible treatments.

Besides anti-depressants a patient suffering from depression may want to consider other forms of treatments either jointly with anti-depressants or by themselves. Obviously qualified medical personnel should help the patient with any of these decisions. Some possibilities for treatments are: counseling, stress-management, relaxation techniques, coping strategies or support groups.

It is important to note that although Parkinson's is a difficult disease for all patients those with depression may suffer from a lower quality of life. It is important to work closely with the medical community to monitor the patient's mood and to help if warranted. Remember not all PD patients suffer from depression, but those that do may need help seeking treatment.

What Do You Want in a Post?

In thinking about my Parkinson's blog post for today I decided that I would love to know exactly what types of topics are of interest to readers so that I can blog about those topics more. So I have a favor to ask. Can you please let me know what topics interest you by leaving a comment on this blog post? If you'd rather email me instead please visit my Profile page and click on the email link.

Let me know if you are interested in postings about PD medications, fundraising or volunteer work, political advocacy, information about the mechanisms behind Parkinson's Disease or something else? I'd love to "hear" your thoughts.

I'm very interested in how to better provide valuable information for the Parkinson's community.

Have a great weekend!

Parkinson's Disease and Brain Prosthetics?"

Could “brain prosthetics” be the futuristic fix for Parkinson’s Disease. Given the fact that Deep Brain Stimulation already uses neural implants hooked up to a type of pacemaker, I say Why Not?

US News and World Report recently had an article about neuroengineers and some neuroengineering work at MIT that could potentially be applied to treat Parkinson’s Disease. (I have to say that I find it fascinating that a discipline such as neuroengineering even exists. Just think if you’d heard about this type of work 20 years ago and what you would have thought.) The article talked about research into robotic exoskeletons, better prosthetic arms and legs, and the most interesting to me, the development of a “tiny LED light switch” that could be implanted into the brain to treat patients with conditions such as Parkinson’s or blindness. The idea is to use this tiny device as a “stoplight, turning neurons on and off in a thousandth of a second.”

Obviously this type of research having real life applications is a little ways off, but I have no doubt that we will see these ideas and therapies becoming realities in the next 10 years. I highly recommend reading this short article. It won’t take you more than 5 minutes.

http://www.usnews.com/articles/science/medical-science/2008/07/24/will-upgrades-enhance-our-bodies.html