People with Parkinson’s are twice as likely to develop heart disease and have a 50% greater chance of dying from it. But why? The perplexing relationship between the two diseases has long troubled scientists. Now, Gerald W. Dorn II, M.D., and his colleague, Yun Chen, Ph.D. from Washington University in St. Louis have reported their findings in the April 26th edition of the journal “Science”. The path to this discovery was not straight and simple. For the past six years, this mystery has eluded scientific explanation.
All cells have mitochondria. Mitochondria are the little “factories” that covert fuel to provide energy to the cells. Brain and heart cells have tremendous needs for fuel and the energy provided by mitochondria. Cells are also equipped with a mechanism to help rid themselves of mitochondria that have stopped functioning or have become sick. If the sick mitochondria are not destroyed and are allowed to accumulate, they no longer manufacture the energy needed by the cell and start using it up themselves thus causing damage or death to the cells. This type of cell damage is what can lead to Parkinson’s or to heart disease. Scientists have understood the process, but did not understand the mechanism of how sick mitochondria could signal to the cell that they were in distress.
The researchers were working with the brains of mice and fruit flies and identified a protein known as mitofusion 2 (Mfn2). The usual role of Mfn2 is to fuse mitochondria together so they can exchange mitochondria DNA, as a form of primitive sexual reproduction. Now they have discovered that mitofusion 2 can change function under certain circumstances, something that no one has ever suspected.
In normal function to maintain cell integrity, mitochondria work to import the gene molecule called PINK. When they collect this PINK molecule, they work to destroy it. However, if the accumulation of PINK becomes too high, the Mfn2 can then change roles and bind with another gene molecule from within the cell itself called Parkin that signals the cell to destroy the mitochondria. In normal conditions, this is how mitochondria and cells undertake house cleaning to maintain cell health and function. But….if you have a mutation in the gene PINK or a mutation in the gene Parkin, you will get Parkinson’s.
Ramond T. Bartus, Ph.D. presented the newest findings of a clinical trial utilizing a new trreatment for Parkinson’s disease. Dr. Bartus is the Chief Scientific Officer and also the Executive Vice President of Ceregene, a San Diego based biotechnology company that is developing gene transfer treatments for neurodegenerative diseases. He was an invited speaker at the May 18th annual meeting of The American Society of Gene and Cellular Therapy which was held in Salt Lake City, Utah.
Dr. Bartus spoke about findings from the second and continuing clinical trial of Cere-120, his company’s gene therapy product to deliver the neurotrophic factor neurtuin to people affected by Parkinson’s disease. Cere-120 is the company’s name for AAV-neurturin. This is a novel way to deliver a neurotrophic factor the brains of Parkinson’s patients. Neurturin is a naturally occurring protein that has successfully repaired and restored injured or dying dopamine producing neurons. In Ceregene’s application, this protein is inserted into a harmless adeno-associated virus (AAV) and is delivered directly to the putamen or substantia nigra regions of the brain by stereotactic injection. Degeneration of neurons in these areas of the brain are responsible for the loss of dopamine and the motor impairments associated with Parkinson’s disease. Neurturin is one of three small proteins that are glial-cell line derived neurotrophic factors (GDNF) that have shown promise in restoring dopamine producing neurons. Neurotrophic factors are proteins responsible for the growth and maintenance of neurons. In both human autopsy and animal studies, it was found that Cere-120 , once delivered to the brain by this highly targeted injection, provides long term, stable and controlled neurturin expression.
Ceregene completed the first clinical trial of Cere-120 in 2009 that demonstrated safety and tolerability and showed some promise of alleviating some PD symptoms. This Phase 2b trial has shown stronger results, but not in all patients. Patients who have been diagnosed for 5 years or less and have not had any prior treatment had higher scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) as well as in other measures of Parkinson’s such as quality of life. Some improvements of overall “off-time” and “on-time without troubling dyskinesias” in patients who had received prior treatment and had been diagnosed for up to 10 years were also noted, but the response was strongest in early-stage patients.
These findings demonstrate that this novel approach to treating neurodegenerative disease deserves more serious consideration and that more carefully planned clinical trials to enroll only early-stage, newly diagnosed and untreated patients will be necessary..Ceregene has conducted 6 clinical trials in both Parkinson’s and Alzheimers. Of 200 subjects enrolled, 100 have received gene therapy products with no serious safety issues. The company plans to continue research in neurotrophic factors via gene therapy delivery for neurodegenerative diseases such as Parkinson’s and Alzheimers.
Dr. Shoukhrat Mitalipov and his lab at the Oregon Health and Science University announced in the journal “Cell” that they have created human embryonic stem cells without using human embryos.. These cells can be used for various types of therapeutic cell repair without fear of transplant rejection because they will genetically identical to the patient. This could lead to important future treatments for such neurodegenerative diseases as Parkinson’s, Huntington’s, ALS and Alzheimers as well as heart and liver diseases.
Dr. Mitalipov’s process for creating this cell line uses cells from tissue, such a skin, to encode the genetics of the patient and fuses it with an unfertilized human egg from a female donor. The genetic material is removed from the nucleus of the tissue cell and implanted into the egg from which the nucleus has been removed. It “tricks” the egg into acting like it has been fertilized, but material in the cytoplasm of the egg causes it to develop into a stem cell. Initially he thought it might take many eggs to achieve this result, but very few eggs were actually required. While similar procedures have been known since Dolly, the Scottish sheep, was cloned in 1996, it has taken many years to perfect the technique. It will now be possible to develop colonies of cell lines which will be able to provide a sufficient quantity of the type of cells that are required for transplantation. To prove that these stem cells can develop into a variety of cell types, including neurons and heart cells, researchers in this lab have performed many series of tests. Although this a major break-through in regenerative medicine, a lot of work still remains to develop safe and effective stem cell treatments for human patients.
Convincing the public of the efficacy of this discovery may prove difficult. Ethical issues abound. Although no previously fertilized eggs or embryos are destroyed in this process, issues remain about paying women to donate unfertilized eggs. Encouraging young and possibly poor women to commercialize products of their bodies is a serious issue. Worries that transplanted genetically engineered cells might have unintended consequences or create harmful mutations have also been expressed.
Other critics fear that this is yet another step closer to creating human clones and are pushing to halt further research until world standards banning human cloning are enacted. Mitalipov does not believe this technique will lead to human cloning. He stressed that cloning of embryos is a dangerous and delicate issue with most artificially created embryos not surviving past implantation. His technique is simply a more efficient way to create stem cells to replace damaged tissues or neurons.
Still other researchers have turned to less problematic methods of producing cell lines by using .adult cells from the patient and inducing them to become the special cells needed. However, there are questions that cells of this type may also have unintended consequences or may not achieve the results expected. Dr. Mitalipov’s lab is currently working on research to directly compare cells derived from both techniques.
A fascinatingly simple study from the University of Waterloo in Ontario, Canada, has shed some light on the effect of darkness on people with Parkinson’s ability to walk. A graduate student completing her Ph.D. in the department of Psychology, Kaylena Ehgoetz Martens, examined 19 Parkinson’s patients using new virtual-reality equipment to understand the effect of sensory perception on freezing gait.
Ms. Martens had each of the 19 participants walk through a doorway or walk into open space at various times. The amount of light available to them was gradually changed each time. As available light was diminished, freezing gait episodes increased. It didn’t matter if it was in the doorway or open space. All participants experienced freezing gait when in complete darkness. Results of this study indicate that impairment in sensory perception function may be the mechanism behind impairment of movement in Parkinson’s disease.
Scientists have long known that nicotine can offer protection from developing Parkinson’s but the risk of cancer from smoking tends to outweigh the benefits. Now a study conducted with 1100 subjects has found that edible sources of nicotine from food plants such as potatoes, peppers, eggplant and tomatoes might also lower the risk of developing Parkinson’s.
Other studies focused on smoking and tobacco use have found nicotine offers some neuroprotection in Parkinson’s. A few studies have even suggested that second hand smoke might also confer some protection against PD which inspired Dr. Susan Searles Nielsen of University of Washington to see if other sources of nicotine might also offer some protection. Tobacco belongs to the solanacea family of plants, as do potatoes, tomatoes, eggplant and peppers. These vegetables also contain nicotine, however in much smaller amounts than tobacco. They are also an important part of a Mediterranean diet, which has long been considered beneficial for people with Parkinson’s.
Dr Nielsen and associates at the University of Washington in Seattle studied men and women newly diagnosed with Parkinson’s and a comparable group of men and women without neurological diagnoses. A medical questionnaire was used to evaluate the participants lifetime uses of tobacco and diet. Use of tobacco included cigarettes, cigars or pipe smoking or smokeless tobacco products.
They found that eating vegetables in general did not confer any risk protection but that eating more vegetables in the solanacea family which contain small amounts of nicotine, did show a trend toward increased protection of risk of Parkinson’s. People who ate vegetables such as peppers, tomatoes and eggplant at least twice a week were 30% less likely to develop Parkinson’s Disease. And people who consumed peppers, that have a higher concentration of nicotine, two to four times a week showed an even stronger trend toward risk protection in Parkinson’s. The effect, however, was the strongest in people who had used little or no tobacco in their lives.
But perhaps it is a bit too soon to rush into a diet that is rich in red or green peppers. While this study may lead to the development of better treatments for Parkinson’s, more research is neede to dtermine the exact mechanism of benefit .
This is the first study to evaluate the benefits of edible nicotine and risk protection in Parkinsons. While it did show a similarity to studies on the protection offered by tobacco use, more studies are needed to confirm these results. Finding a less toxic source of nicotine such as peppers could lead to more innovative approaches for the prevention and treatment of Parkinson’s.
Visualizing nerve damage as an electrical cord with a short in it helped researchers at Tel Aviv University in Israel devise a potential treatment to reverse nerve damage. They visualized and then developed a tube running between the damaged nerve ends to restore function and eliminate pain. This special micro-tube is filled with a gel that contains three special ingredients to encourage the repair and re-growth of the damaged neurons: Antioxidants that give anti-inflammatory benefits; synthetic laminum peptides to provide a track along which new neurons can grow and hyaluronic acid to keep the tube from drying out. The tube itself is biodegradable. The special gel has also been used alone in cell therapy and has been proven to preserve cells and encourage cell growth.
While it is still a ways away from being used in humans, animal studies have been successful and the developers of this technology are hopeful that it will be available within a few years. They see this development as helping people with paralysis and other nerve damage problems as well as using the gel in cell therapy to help the symptoms of Parkinson’s.
Nerves can be soothed or set ajar by the sounds of music. But just how does that happen? Film directors know how to use music to enhance a scene, raising the tempo to accompany a race or employing certain harmonies to enhance mystery. TV and radio ads are accompanied by musical jingles to stick in the minds of future consumers. So just what is the connection between neurology and music?
An on-going public symposium is part of an honors course being offered at University of Central Florida called “The Music and The Brain” taught by two professors, one a neurologist and the other a musician. The symposium combines both musical performance and neurological commentary.
Dr. Kiminobu Sugaya is the neurologist who comments on the science behind emotional responses to music. “Music cn act on the same place and release the same chemicals (dopamine) in the brain that drugs do, in the pleasure centers”, he said. Music can be used as a pleasant stimulant for both Alzheimer’s and Parkinson’s patients. But music can also become a torture and a cause for epileptic seizures in muicogenic epilepsy.
There are theories “that certain major scales provoke certain emotions in people” said Professor of music, Ayako Yonetani. “But the question about the connection of the mind and music is one that everyone is trying to answer.” Professor Yonetani said that musicians strive to evoke an emotional effect on their listeners such as the theme from “Schindler’s List” and Bach’s “Air on the G-String.
Although the neurological implications of music are not yet thoroughly understood, both Dr. Sugaya and Dr. Yonetani are excited to see more diverse involvement in neuroscience protrams. Dr. Sugaya suggests that in addition to chemistry, psychology, computer science and even journalism can all contribute to a better understanding in the field of neurology.
Investigators found that the use of the leukemia drug nilotinib in mice specially bred to over express alpha-synuclein and tau was successful in eliminating the abnormal accumulations of these proteins. They also found that cognition (thinking) as well as movement and functional skills were also greatly improved by the use of this drug in these mice. And the mice actually lived longer than the untreated mice. Alpha-synuclein and tau proteins are the main causes of Lewy Body dementia in Parkinson’s and other neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s and Huntington’s. It is an excess of these abnormal proteins that cause brain cells to deteriorate and be destroyed.
The investigators in this group had been searching to find a drug that could cross the blood-brain barrier in order to destroy cancerous tumor cells in the brain. Nilotinib was one drug that had that ability. When used in much higher concentrations to treat chronic myelogenous leukemia, the drug forces cancer cells to turn on themselves and totally self destruct. The researchers reasoned that very small doses might be sufficient to rid brain cells of only the malfunctioning proteins. Nothing like this had ever been done before.
The research group from Georgetown University is led by senior researcher Charbel E-H Moussa, M.B., Ph.D. He says “This drug, in very low doses, turns on the garbage disposal machinery inside neurons to clear toxic proteins from the cell.” Dr. Moussa also said “We successfully tested this for several disease models that have an accumulation of intracellular protein. It gets rid of alpha synuclein and tau in a number of movement disorders, such as Parkinson’s disease as well as Lew body dementia.” Dr. Moussa feels that for this treatment to be most effective, it would need to be used early in the neurodegenerative disease.
He is currently planning a phase II clinical trial in patients who have already been diagnosed with alpha synuclein inclusions such as Lewy Body dementia and Parkinson’s. He notes that the drug already had FDA approval for leukemia and it is well tolerated in humans. Hopefully, this will help to this clinical trial sooner rather than later. The researchers are very optimistic and eager to proceed with this trial.
The Parkinson Research Foundation (PRF) has provided a $30,000 grant donation to help support a research study being conducted in conjunction through the University of Florida in Gainesville.
The study will look take a closer look at the efficacy of aerobics and dance classes, which are specifically tailored for people with Parkinson’s. According to Marilyn Tait, Executive Director of Parkinson Place, the medical community has accepted that exercise is essential for Parkinson’s patients, but not integrative dance or yoga. There really aren’t any treatments out there that incorporate specific exercise types of exercise programs for people with Parkinson’s.
This type of study is of particular importance because has been little research done on the effect of aerobics and dance on Parkinson’s patients. According to Tait, the medical community’s primary treatment for Parkinson’s is medication and alternative treatments need data to back up their validity. The last studies done on the topic were 10 years ago and never got published.
Heading up the research study is Jill Sonke, Director of the Center for the Arts in Medicine at the University of Florida. Sonke is one of the faculty members of the School of Theatre and Dance and serves as the Assistant Director and Artist in Residence with Shands Arts in Medicine. Her specialty is dance in medicine.
“I think the results of the study are going to cause health care providers that see Parkinson’s patients to make this an important part of treatment,” said Larry Hoffheimer, founder of PRF.
A principal mission of the PRF is to educate patients and their care givers – enabling them to live fuller and more comfortable lives. PRF holds seminars, conferences, and educational cruises.
“Success Strategies for Parkinson Caregivers”
By MARILYN TAIT
Parkinson Educator, Motivator & Advocate
Executive Director, Parkinson Research Foundation
SPEAK UP! “Keep Talking When No One Wants to Listen”
The non-stop highs and lows of caregiving put you on an emotional roller coaster whether you like it or not. Unfortunately, the emotions often associated with caregiving are far from calming. Anxiety, frustration, anger, loneliness, depression and fear can make for a rough ride.
Uncontrollable mood swings can take the joy from the day and rob you of a peaceful night’s sleep. It’s common for long-term caregivers to feel the increased pressure of rising demands but for the good of all you must remain calm. The key is to let your feelings out a little at a time before you explode. The fastest and easiest way is to keep opening your mouth. There will never be a better time to talk too much!
- Share your thoughts with family members and friends whom you can trust with your feelings. Identify those who will listen objectively while offering sound advice and sincere concern. Gain strength and emotional support from those in your life who love you enough to listen.
- Right your feelings by writing them down. Journaling is an easy and effective way to release negative feelings the minute they pop up. Write at random. If your feelings are important enough to matter, they are important enough to write down.
- Keep the line of communication open between you and your loved one. Do not hold negative feelings in because it’s easier to say nothing. No one can read your mind. If you want others to know what you are feeling, tell them.
- Talk to yourself. Rely on the one who cares the most and is always ready to listen. When you’re down, pick yourself up with praise and positive affirmations. Always pat yourself on the back and silently take a bow.
- Seek counseling when the emotional impact of caregiving knocks you down and you can’t get up. If you try in vain to deal effectively with your feelings, do not hesitate to make an appointment with a professional counselor who can provide the necessary resources and emotional support you need.
Message from Marilyn…
If you cherish your sanity, speak up! There is no good reason to harbor your feelings. As a caregiver, think about what you are dealing with, physically and emotionally, and love yourself enough to open up and let your feelings out. Your mission is to maintain a positive relationship between you and your loved one. The caregiving challenges you face together, every day, have the ability to negate the finest relationship. To protect what you love the most, keep talking no matter what!