Politicians Debated Stem Cells While Scientists Went Out and Made Them Work

People with Parkinson’s disease can borrow hope from the ongoing success of stem cell therapies that reverse type 1 diabetes — despite political maneuvering and legislation that could potentially slow stem cell research. If stem cell scientists can make damaged pancreas cells produce insulin again, they may also be able to figure out how to use stem cells to restore substantia nigra function and restart dopamine production in people with Parkinson’s. Thankfully, the scientists have gone to work and turned their backs on the political bickering.

There is a series of successful stem cell experiments in type 1 diabetes patients. A team of researchers from the Walter and Eliza Hall Institute of Medical Research in Australia reported stem cell success in late 2012. Another University of Illinois scientist reported encouraging stem cell results in early 2012.

In 2009, a JAMA article reported on the ongoing progress of a group of previously diabetic patients who had lived without daily insulin injections for more than five years. This same group of type 1 diabetes study participants prompted the following blog post in March 2007 when many of the patients had just passed the three-year insulin-free milestone.

Today, as the cameras were rolling on Capitol Hill, the US Senate debated stem cell ethics legislation (link no longer available). Yet a more notable “giant leap” occurred — also today — in Brazil when a group of physicians reported temporarily reversed Type I diabetes in fourteen patients.

What does this mean for people living with Parkinson’s disease? If scientists can manipulate stem cells into becoming pancreas cells that produce insulin, they could someday figure out how to program stem cells to become dopamine producing cells. If they succeed, they could reverse Parkinson’s disease, and they may even produce the cure.

It is also worth mentioning that the doctors in this diabetes study used the patients’ own adult stem cells to carry out this feat. So, there is little debate about stem cell ethics because no fetal cells were used.

Thank you scientists for plowing ahead with stem cell research despite the obstacles. We hope that funding and innovation will give medical experts more tools in the very near future for stem cells to cure Parkinson’s disease and many other health conditions.

You can read another related story from USA Today:

Stem cells ‘reset’ to fight diabetes

Domperidone – Comeback May Still Find Place in Parkinson’s Disease

This post was initially published in the blog My Parkinson’s Info on February 26, 2007

An old pharmaceutical favorite, domperidone, is back in clinical trials for people with Parkinson’s disease. About 20%percent of people taking dopamine agonists, such as Mirapex and Requip, experience some swelling in their legs (edema). The current research is exploring domperidone’s ability to relieve the swelling, in a Phase II clinical trial. In addition, the medication’s ability to speed digestion and relieve constipation is a highly desirable side effect.

Domperidone has an interesting history, which entails more questions than answers. In the Parkinson’s community it is best known for helping people overcome constipation symptoms. It seems to help the intestines get things going. However, when domperidone was presented to the FDA, along with some good clinical evidence for its effectiveness, the FDA did not approve it. Furthermore, the FDA did not directly address questions about its decision.

Domperidone also stimulates milk production in breast-feeding mothers. However, it produces some significant undesirable side effects, and there is ample controversy about the risks versus the value of the benefits. So, it is easy to speculate that the FDA may have acted to keep domperidone out of American pharmacies completely to avoid tackling the safety issues that crop up when using it to increase milk production.

There is a loophole, however. If you want to use domperidone to improve digestion, your physician can open an Investigational New Drug Application on your behalf. After the application is open, people with Parkinson’s disease can often order domperidone from pharmacies outside of the United States.

What is Idiopathic Parkinson’s Disease?

This post was initially published in the blog My Parkinson’s Info on March 12, 2007

Sometimes when you hear people talk about Parkinson’s disease, you will see the term “idiopathic” attached to it. Idiopathic means that an event’s cause is unknown and its arrival is an unexpected surprise.

Most cases of Parkinson’s are idiopathic because we do not know where they came from. Science has just not figured out what chain of events sparks most cases of Parkinson’s disease. Idiopathic Parkinson’s disease is also called “primary Parkinson’s disease.” In that minority of cases where genes, injuries or toxins may be involved they call it “secondary Parkinson’s disease”. It is secondary, because it follows the injury, toxic event or genetic mutation that was the primary event.

As research progresses, medical scientists will learn more about what causes Parkinson’s disease. We will have less idiopathic and more secondary Parkinson’s disease simply because we’ve figured out what causes more cases.

Clusters of Related Genes May Cause Parkinson’s Disease

This post initially appeared on the blog My Parkinson’s Info, on June 22, 2007

The following story discusses genetics and Parkinson’s disease in detail. If you are unfamiliar with genetics, we encourage you to read two very basic stories about genetics:

An Easy Course in Genes and Genetics

Clusters of Related Genes May Cause Parkinson’s Disease
ROCHESTER, Minn. — A new Mayo Clinic study provides strong evidence that the combined effects of common DNA changes (mutations) in several genes largely explain why some individuals get Parkinson’s disease while others don’t. These genes may even predict with great accuracy at what age people might develop their first symptoms.

The findings are published in the June 15 issue of PLoS Genetics.

“This represents a major paradigm shift from single gene studies to genomic pathway studies of complex diseases,” says Demetrius Maraganore, M.D., the Mayo Clinic neurologist and Parkinson’s disease specialist who led the study.

The authors say traditional genetic studies have either discovered rare single gene mutations that cause Parkinson’s disease only in isolated families. Or some studies have identified common single gene variants that are only slightly associated with the disease.

“By examining a large cluster of related genes, we found patterns that make people up to 90 times more likely to develop Parkinson’s than the average person,” says study co-author Timothy Lesnick, a Mayo Clinic biostatistician. “The size of the effects that we observed for genes within a pathway and the statistical significance of the predictive models were unprecedented.”

The models were highly accurate in predicting age of onset of the disease:

  • By age 60, 91 percent of patients in the highest-risk group, the group with the most gene clusters, already had Parkinson’s, while only 11 percent of patients in the lowest-risk group did.
  • By age 70, every member of the highest-risk group had the disease, where as two-thirds of patients in the lowest-risk group still were disease-free.
  • Members of the highest-risk group typically developed Parkinson’s more than 20 years earlier than the lowest-risk group.

 

The study is significant because:

      1. It investigated not just one, but many genes that were predicted to interact in a specific biologic pathway.
      2. It provides intriguing new insights into the symptoms of Parkinson’s disease, and may lead to tests to identify persons at high risk and to new treatments to prevent the disease or halt its progression.
    3. These high-risk Parkinson’s disease genes were contained in the biologic pathway for the development of the human brain, as well as repair and remodeling of brain circuits. This raises speculation for another environmental influence that heretofore has been ignored: pre-birth events in the mother’s womb.

 

How the Researcher’s Performed this Study
The researchers studied the axon guidance pathway, which includes at least 128 genes that encode proteins that play a critical role in guiding the axons (or wiring) of the brain during fetal development. The same proteins also repair the wiring and determine the fate of damaged brain cells later in life.

The Mayo researchers analyzed a dataset that included information for hundreds of thousands of common DNA variants (single nucleotide polymorphisms or “SNPs”) in 443 Parkinson’s disease patients and in 443 control subjects; the controls were unaffected siblings. Researchers identified SNPs within axon guidance pathway genes and used statistical methods to identify combinations (“models”) of SNPs that were highly predictive of susceptibility to Parkinson’s disease, survival free of Parkinson’s disease, and age at onset of Parkinson’s disease. They then validated their findings using data from additional whole genome DNA and RNA variation datasets for Parkinson’s disease.

The Story that Led to the Discovery
Dr. Maraganore and Mayo colleagues published the first whole-genome association study of Parkinson’s disease in 2005, studying hundreds of thousands of common DNA variants in the human genome, but as single and unrelated risk factors. They identified a dozen DNA variants (changes or mutations) that were weakly associated with Parkinson’s disease, but those findings have since been difficult to replicate. Their most significant finding was for a DNA variant within the axon guidance pathway. This was the key clue in that first study, leading them to predict that this axon guidance pathway needed to be investigated. Thus, they focused on a few thousand variants within genes that encode that pathway, and analyzed their joint effects. Dr. Maraganore compares the change in method to the difference between gazing at faint stars with a telescope versus looking at the Milky Way with the naked eye. “Instead of straining to observe the effects of single DNA variants scattered randomly across the universe of the human genome, we observed the effects of a constellation of variants within a well-defined genomic pathway,” he says. “When we looked at the axon guidance pathway in Parkinson’s disease in this way, it lit up.”

Implications for Patients
Parkinson’s disease is an aging-related disorder that affects nearly a million Americans. The cardinal signs include tremors, slowness of movements, and rigid body and limbs. The symptoms predominantly arise from progressive degeneration of brain cells that produce the chemical dopamine. “It is intriguing to consider that patients with Parkinson’s disease may be wired differently from birth,” adds co-author Eric Ahlskog, M.D., Ph.D., the head of Mayo Clinic’s Movement Disorders Section. “This might explain lifelong differences in personality, including avoidance of addictive substances and increased anxiety and depression. It also might explain asymmetries in the movement disorder that occurs in Parkinson’s disease; typically, one side of the body is affected predominantly.”

The findings could quickly lead to genetic tests to identify persons with a high probability of developing Parkinson’s disease during their lifetime. For example, a person with high predicted probability could have a risk of Parkinson’s disease that is 90 times greater than the average person; members of intermediate-risk groups would be 4 to 25 times more likely to develop Parkinson’s. The findings may also lead to development of new treatments that would promote the repair of damaged axons in the brain and spare nerve cells from early death, which could prevent or slow the progression of the disease.

Maternal Health Factors
Researchers say that just as subtle genetic variations within the axon guidance pathway might alter brain wiring during fetal development and predispose to Parkinson’s disease decades later in life, subtle maternal health factors also could alter brain wiring and predispose to the disease.

The researchers say effects of maternal health on the risk of Parkinson’s disease should be explored in future studies. Until now, environmental studies of Parkinson’s disease have largely focused on adulthood exposures, such as to pesticides, smoking and coffee. These same exposures might contribute to the cause of Parkinson’s disease during gestation, they suggest.

The study was supported by grants from the National Institutes of Health, the Michael J. Fox Foundation, the National Parkinson Foundation Inc., and Gene Logic Inc.

Source: Mayo Clinic New Release

The Caregiver’s Role

This post was initially published on the blog My Parkinson’s Info on February 3, 2006.

If you are reading this blog, chances are you are very grateful for a concerned caregiver, or you are a caregiver yourself. The role of caregiver can include counselor, listener, exercise partner, reader, feeder, dresser, bather, medication manager, driver, and many other titles. Many caregivers perform this admirable service as a voluntary labor of love. There is also a formidable army of health care workers that contribute immensely to PD care.

The webcast, Parkinson’s Disease Through a Caregiver’s Eyes , gives insight into the role of a caregiver wife.  Guisla Schafstellar cares for her appreciative husband, Helmut. She personifies the many concerned caregivers so entrenched in the PD world. Certainly many readers will identify with her patient demeanor and helpful disposition.

More importantly, be sure and thank a caregiver at the next opportunity. Please let us know about the experiences you have as a caregiver. Certainly, there are overwhelming challenges. We hope that there are some satisfying experiences and memories as well.

Amantadine May Slow the Onset of Dementia in People with Parkinson’s Disease

This article was initially published in November, 2006 edition of the My Parkinson’s Info Newsletter.

A convincing study of 593 patients explored whether or not amantadine could slow the progression of dementia in people living with Parkinson’s disease. It turns out that patients that took amantadine took an average of 9.7 years to reach dementia, while those who did not take it averaged 5.9 years. If these numbers hold true across the general population, amantadine would provide the average person a delay of four years before they confront full-blown dementia.

The study also found that the minds of people who took amantadine prior to the onset of dementia did not worsen as rapidly.

This study that is the result of an Italian-Israeli collaboration, and was published in the journal < I>Movement Disorders. The study is strong because it included a large group of 593 patients.

Men as Caretakers for People Living With Parkinson’s

This article was initially published in October, 2006 edition of the My Parkinson’s Info Newsletter.

Some people think that it is dangerous to use stereotypes. They are probably right most of the time because there are some stereotypes comparing men and women that are quite inaccurate. Whether the labels are accurate or not, society often likes to ascribe attributes such as caring, compassionate, patient and nurturing to women. Feminism has questioned this, and helped to confirm or debunk some of these stereotypes. If we assume that the “fairer sex” has this sensitive set of attributes in abundance, we would also have high expectations of women as caregivers. Naturally we would assume that men would struggle as compassionate caregivers.

The truth is, that every person is different. There are men and women that are going to excel at care giving; and there are a good number from each side of the gender fence that will struggle with the abilities and talents that would make them a naturally good caregiver. Remember, we can all learn and improve. A very skilled electrician got there by learning, doing some experimenting, and a amassing a lot of experience. The same is true for a caregiver. If you’re not a natural, be patient with yourself, and allow yourself to do gradually better. The person you are caring for will likely notice your improvement, and will certainly appreciate it over time.

Men, Consider the contribution of Dwight Link to his wife of fifty years. She recently passed away; but, Parkinson’s disease intruded on their marriage for over two decades