Pesticides and the Genetic Link

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Pesticides and the Genetic Link

The central valley of California is a major producer of all the fruits and vegetables consumed, not just in the United States, but all over the world.  Production of huge yearly crops depends upon serious planning and management, including the use of herbicides and pesticides.  So three counties in this major agricultural region (Fresno, Kern and Tulare) became a very appropriate laboratory to study the effects of pesticides for Jeff M. Bronstein, MD, PhD, professor of neurology and director of Movement Disorders at the Geffen School of Medicine, University of California at Los Angeles.

His team developed a study, The Parkinson’s Environment and Genes (PEG) Study that recruited subjects from three of the most agricultural counties in the state of California.  In the laboratory they found that many pesticides inhibit aldehyde dehydrogenase (ALDH) activity and this inhibition is also associated with risk of developing PARKINSON’S DISEASE.  So the team tested 26 different pesticides and found only four structural classes of ALDH inhibiting pesticides that contribute to the risk of developing PARKINSON’S DISEASE.  .

All humans carry a gene for ALDH, but not all humans exposed to pesticides develop PARKINSON’S DISEASE Interestingly, some people carry polymorphisms (slightly different versions) of the ALDH gene, and if they have no exposure to pesticides they do not develop PARKINSON’S DISEASE.  Also, the study suggests that only about 6 per cent of people exposed to ALDH inhibiting pesticides actually develop PARKINSON’S DISEASE.

However, if a person carries a polymorphism for the ALDH gene, the, exposure to ALDH inhibiting pesticides increases the risk of developing PARKINSON’S DISEASE proportionately to the number of pesticides to which they are exposed.  If a person was exposed to one, there was risk, but if they were exposed to six, the risk would be 6 times higher, and most people exposed to pesticides in the agricultural community are exposed to many.  A six fold greater risk is enormous. The study also looked at whether a person was exposed only at work or only at home or at both and found much higher correlations when the exposure was at both work and home.

Inhibition of ALDH is thought to occur thru a chemical, dihydroxyphenylacetaldehyde (DOPAL), which is a dopamine derivative.   And therein lies a potential target to lower the risk through inhibiting the enzyme that makes DOPAL. Dr. Bronstein notes that there are already drugs on the market that can protect against pesticide poisoning, but finding the 6 percent of the population that is at risk would be difficult to accomplish.

This study is an early but important step in showing mechanism of action between genetics and the environment in PARKINSON’S DISEASE and also to the number of exposures.  It helps explain why the connection between pesticides and PARKINSON’S DISEASE which has long been suspected but was so difficult to prove.  This study should bring more interest and research into this area to protect the people that are exposed to pesticides and to perhaps help develop less toxic pesticides that do not inhibit ALDH.  It also seriously enforces the attention to regulation and safety issues for storing and handling pesticides as well as the methods of application.

J.M. Bronstein et al; How Pesticides May Boost Parkinson’s Risk; Neurology, 2014; 82:419-126

 

Review by Marcia McCall

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Better Thinking and Less Depression with Higher Levels of Vitamin D

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Better Thinking and Less Depression with Higher Levels of Vitamin D

Amie L. Peterson, M.D. is first author on a study that was published in The Journal of Parkinson’s Disease that reports that higher Vitamin D levels in early PARKINSON’S DISEASE improve performance on cognition and mood tests.  This study may open new interventions to prevent cognitive decline if started early in the course of the disease.  Dr. Peterson is on the staff of Oregon Health and Sciences University.

The study examined vitamin D levels of 286 subjects and tested their performance in a battery of tests designed to measure memory and cognitive skills as well as indications of mood, such as depression.  61 of the subjects were considered to be demented, and their testing scores also showed a correlation to lower levels of vitamin D.  For the remainder of the group, higher levels of vitamin D did correlate to better performance with memory and recall tests as well as ability to name images of animals and vegetables.  They were also found to be less depressed as measured on a well known depression scale.

It was not known if any of the subjects in the study were currently taking supplements of vitamin D, nor is the authors willing to comment on whether or not vitamin D was the cause of the improvement.  They speculate that more advanced subjects who already were slowed by the disease and dementia were less able to get outside and had limited exposure to sunshine, the major source of vitamin D.  The results do suggest that there is a strong correlation between higher levels of vitamin D and better cognition with less depression.  Because cognitive impairment early in the course of PARKINSON’S DISEASE may predict the development of dementia in later stages, anything that slows the development of cognitive problems could improve the quality of life and slow the course of the disease for people in the early stages.

 

“Memory, Mood, and Vitamin D in Persons with Parkinson’s Disease,” by Amie L. Peterson, Charles Murchison, Cyrus Zabetian, James Leverenz, G. Stennis Watson, Thomas Montine, Natasha Carney, Gene L. Bowman, Karen Edward, and Joseph F. Quinn. Journal of Parkinson’s Disease, Volume 3/Issue 4, DOI: 10.3233/JPD-130206

Review by Marcia McCall

 

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Apomorphine for Treatment of Advanced Symptoms of PARKINSON’S DISEASE

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Apomorphine for Treatment of Advanced Symptoms of PARKINSON’S DISEASE

Apomorphine has been available for many years as a “rescue” drug to help people with symptoms of advanced PARKINSON’S DISEASE, such as becoming frozen or having debilitating “off” periods. Because of its serious side effects has not been a drug of choice for many neurologists or patients.  Apomorphine needs to be injected under the skin, which is painful and causes scaring. Once injected, it causes immediate nausea and vomiting; plus it needs to be maintained in an acidic composition.  All of these ‘side effects’ make it a difficult remedy for an already too difficult set of symptoms.

Many pharmaceutical companies have tried for many years to find a viable formulation and delivery method to make Apomorphine more convenient and helpful for people with PARKINSON’S DISEASE.  It has been put into patches, pumps and suppositories, and none of them have been effective in getting sufficient quantities of the medication into the bloodstream without causing major irritations or side effects.

The Canadian company Cynapsus has now developed a novel packaging and delivery method that avoids the adverse reactions with this medication.  They have packaged in in a thin filmstrip that dissolves under the tongue, similar to the strips of mouthwash product, Listerine. The medication is embedded in the filmstrip, called APL-130277, which maintains the acidity until it dissolves in the mouth, and it is able to penetrate into the bloodstream within two minutes.  It is not quite as fast acting as the injected form, but if negotiations with the Food and Drug Administration go well, the company will be moving ahead with clinical trials this summer.  Because Apomorphine is already a known and approved medication, safety trials will not be necessary, which should also help speed this product to market.

Source:   http://www.fiercedrugdelivery.com/story/cynapsus-sublingual-strip-severe-parkinsons-reduces-side-effects-study/2014-01-14

 

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http://www.netdoktor.de/Krankheiten/Parkinson/Therapie/Parkinson-Medikamente-Apomorp-11973.html

PARKIN Mutation Carriers Progress Slower than Idiopathic PARKINSON’S DISEASE

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PARKIN Mutation Carriers Progress Slower than Idiopathic PARKINSON’S DISEASE

If there is any such thing as good news in PARKINSON’S DISEASE, perhaps it is that people who have young-onset and carry the autosomal recessive gene for PARKIN mutations have a slower decline of motor symptoms and maintain higher cognitive functioning.  While being diagnosed with young onset PARKINSON’S DISEASE is certainly not good news, these people may benefit from the assurance that their disease will progress more slowly and that they are at a lower risk for developing dementia than people diagnosed with idiopathic PARKINSON’S DISEASE.

A study of 44 subjects over a period of 14 years compared 21 subjects who carried the PARKIN mutation to 23 subjects who did not.  Those who carried the mutation had an earlier age of onset and were younger than the subjects in the idiopathic cohort.  These young onsets performed better on Mini-Mental State Examinations and had lower scores (indicating better performance) in Clinical Dementia Rating tests.  They also scored higher in cognitive domains and did better in tests of visuospatial relationships, attention and memory. Motor performances were also better than those in the idiopathic cohort.

Primary researcher Dr. Roy N. Alcalay who is with Columbia University in New York says “our findings have important implications for genetic testing and for the counseling of homozygotes and compound heterozygotes that carry PARKIN mutations.”  He also stresses that this was a small, cross sectional study and that more longitudinal studies need to be done to confirm these findings.

Alcalay, R.N, et al; Cognitive and Motor Function in Long-Duration PARKIN-Associated Parkinson Disease; JAMA Neurol 2014; 71(1) 62-67, doi:10.1001/jamaneurol.1023.4498

 

Review by Marcia McCall

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Clinical Trial Considers Inosine Safe and May Lead to Future Treatments to Slow the Progression of PARKINSON’S DISEASE

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Clinical Trial Considers Inosine Safe and May Lead to Future Treatments to Slow the Progression of PARKINSON’S DISEASE

Michael Schwarzschild, M.D., Ph.D. who is connected to the Harvard School of Public Health and Massachusetts General Hospital has been conducting research with urate levels for many years.  In a report issued in May 2012, he stated that they had rather unexpectedly found that people who had higher levels of urate (uric acid) also had a lower than average chance of developing PARKINSON’S DISEASE.  In that study, they found that urate served as an antioxidant that could protect cells from cell death, however it required the assistance or cooperation of neighboring cells, called astrocytes. Astrocytes are cells that provide both structural and metabolic support to neurons and it is their intervention that determines how the urate is used within the neural cells. The next question was to find out if urate increased artificially would provide the same protection as urate produced naturally.

The results of that study have found that Inosine, a precursor to uric acid, could be added to increase urate and that the results were safe and tolerable.  To accomplish this they enrolled 75 very early onset people with PARKINSON’S DISEASE who had not yet begun taking any dopamine replacement therapy and who also had very low levels of urate in a two year study.  Inosine occurs naturally in the human system, as a product of normal metabolism.  Inosine given in this study was in pill form, which meant it had to be broken down via the digestive system. Two well known side effects of high uric acid levels are gout and kidney stones, so these potential effects were carefully monitored during the study.  While kidney stones were developed in three of the participants, in two of the participants they were not related to the levels of urate and all were resolved successfully.  After six months in the study, 95 per cent of the participants had no difficulties taking the Inosine drug.

The strengths of Inosine tested on these participants showed an increase in urate levels in both blood and cerebrospinal fluids.  One month after stopping the medication, the urate levels of all participants returned to their pre-study levels.  The safety and tolerability data together with some early data on effectiveness looks very encouraging  “These results support advancing to a larger trial capable of addressing whether Inosine might fill the critical unmet need for a disease-modifying treatment.” says Dr. Schwarzschild.  He and fellow investigators are moving toward the development of a much larger phase 3 trials which will study specifically the benefits and effectiveness of Inosine.

Urate levels increased artificially could have potentially serious side effects, so Inosine is not yet considered a safe treatment for PARKINSON’S DISEASE.  “We know that excessively high urate can lead to kidney stones, gout and possibly other untoward effects, which is why attempts to elevate urate are best pursued in carefully designed clinical trials where the risks can be reduced and balanced against possible benefits, ” cautions Dr. Schwarzschild.

Michael A. Schwarzschild, MD, PhD; Alberto Ascherio, MD, DrPH; M. Flint Beal, MD; Merit E. Cudkowicz, MD; Gary C. Curhan, MD; Joshua M. Hare, MD; D. Craig Hooper, PhD; Karl D. Kieburtz, MD; Eric A. Macklin, PhD; David Oakes, PhD; Alice Rudolph, PhD; Ira Shoulson, MD; Marsha K. Tennis, RN; Alberto J. Espay, MD, MSc; Maureen Gartner, RN, MEd; Albert Hung, MD, PhD; Grace Bwala, MBBS; Richard Lenehan, MD; Elmyra Encarnacion, MD; Melissa Ainslie; Richard Castillo; Daniel Togasaki, MD, PhD; Gina Barles; Joseph H. Friedman, MD; Lisa Niles, MS; Julie H. Carter, RN, MN, ANP; Megan Murray, MA; Christopher G. Goetz, MD; Jeana Jaglin, RN, CCRC; Anwar Ahmed, MD; David S. Russell, MD, PhD; Candace Cotto, RN; John L. Goudreau, DO, PhD; Doozie Russell; Sotirios Andreas Parashos, MD, PhD; Patricia Ede, RN; Marie H. Saint-Hilaire, MD; Cathi-Ann Thomas, RN, MS; Raymond James; Mark A. Stacy, MD; Julia Johnson, MD; Lisa Gauger, BA; J. Antonelle de Marcaida, MD; Sheila Thurlow, MSN, BSN; Stuart H. Isaacson, MD; Lisbeth Carvajal; Jayaraman Rao, MD; Maureen Cook, RN, BSN; Charlise Hope-Porche, RN; Lauren McClurg; Daniela L. Grasso; Robert Logan, MS; Constance Orme, BA; Tori Ross; Alicia F. D. Brocht; Radu Constantinescu, MD; Saloni Sharma, MBBS; Charles Venuto, PharmD; Joseph Weber; Ken Eaton. Inosine to Increase Serum and Cerebrospinal Fluid Urate in Parkinson Disease: A Randomized Clinical TrialJAMA Neurology, December 2013

Review by Marcia McCall

 

 

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Pharmacoperones – A New Way to Rescue Cells

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Pharmacoperones – A New Way to Rescue Cells

While it appears to be a new technology, it has been a research project for 13 years and is finally showing beneficial effects in mouse models of disease.  The procedure that has taken so long to develop has actually reversed a serious reproductive deficit in male mice.  The condition in mice is parallel to the condition in humans, and the method perfected on mouse cells will also translate to human cells.  This will be a major advance with wide ranging applications, particularly for neurodegenerative diseases such as PARKINSON’S DISEASE, Huntington’s disease and Alzheimer’s, among others.

When proteins such as alpha synuclein enter cells, they need to form a three dimensional structure in order to properly perform their function within the cell. When they do not form the proper structure, they are considered mis-folded proteins, which ultimately cause the cells to die.  What this research has shown is that there are small molecules, which serve as a sort of “quality control” system, and when they encounter the misfolded proteins, they are unable to re-direct them thus causing them to fail.  Use of another small molecule, a pharmacoperone, as a chaperone can enter the cell and serve as a scaffold to help the misfolded protein fold into the proper shape and then return to function.  What is unique is that now they have found drugs to monitor the “quality control” system that can re-direct the misfolded proteins and rescue the cells.  This is a whole new approach that may soon be able to cure a range of diseases

The team of researchers from Oregon Health Sciences University consisted of JoAnn Janovick and Michael Conn both of whom have recently left Oregon to join Texas Tech University Health Sciences.  They were assisted in their research on this project by Richard, Behringer, M.David Stewart, Douglas Stocco and Pulak Manna.  The research paper will be published in an early online edition of the Proceedings of the National Academy of Sciences.

Having seen such exciting and positive results in the mouse model, Dr. Conn is anticipating that clinical trials with humans will not be far in the future.  Similar research is being carried out in other institutions for the treatment of diabetes, inherited cataracts and cystic fibrosis.  Look for more exciting news and developments to come from this research in the near future.

Source: ohsu.edu/xd/about/news/2013/12-09-ohsu-researchers-develop.cfm

 

Review by Marcia McCall

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PARKINSON’S DISEASE Treated via the Computer

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PARKINSON’S DISEASE Treated via the Computer

How would you like to have your next visit with your PARKINSON’S neurologist in the privacy of your own home?  What if you didn’t have to travel to the office and could still have the benefit of an office visit?  Or if you were able to have the benefit of consulting a specialist who may be too far away to actually visit in person?   It may be coming sooner rather than later.

Allison Willis, M.D. did a chart review of 138,000 people diagnosed with PARKINSON’S DISEASE and was alarmed to find that more than 40% of them never had the benefit of seeing a movement disorder specialist.  She also found that 40% of them who did have the benefit of a neurologist had a 22% reduced risk of death and a 21% reduced risk of entering nursing home care.  And only about 8% of the people with PARKINSON’S ever saw a movement disorder trained neurologist.

Peter Schmidt, Ph.D., has a degree in biomedical engineering.  He was challenged by the numbers in Dr. Willis’ study and thought there must be a better way to connect patients with trained neurologists.  So he worked out the technical issues between the math and medicine.  Ray Dorsey, M.D. is a movement disorder trained neurologist at the University of Rochester Medical Center.  Previously, he and another neurologist had developed and piloted a telemedicine program of PARKINSON’S patients in a nursing home.  The next challenge was taking the telemedicine program to other people with PARKINSON’S DISEASE.  He used a $50,000 grant from Verizon and was able to consult via high speed internet connection with patients in their homes.

Working together with Dr. Schmidt and other colleagues, they were able to write a proposal that would allow them to connect with about 200 patients in their homes.  They received a $1.7 million dollar grant and since May of this year has been able to provide telemedicine care to about 100 people and hope to expand that to 200 people.  The project has so far covered only 5 states, and provides a one time telemedicine consultation for free.  Considering that there are few PARKINSON’S specialists spread far and wide and many, many people with PARKINSON’S, this may prove to be a much better way to provide people with the benefits of a specialist’s knowledge and use the doctors’ clinical skills more effectively.    It may not be quite as good as a visit in person, but it is better than no visit to a specialist at all.  The future will surely see many technological improvements.  Dr. Dorsey’s vision is that “anyone with PARKINSON’S, anywhere can get the care they need.”

Vinayak Venkataraman, Sean J. Donohue, Kevin M. Biglan, Paul Wicks, E. Ray Dorsey. Virtual visits for Parkinson diseaseNeurology: Clinical Practice, December 2013

Wilis,  A>W>,  Schootman, M., Evanoff, BA, et al. Neurolgist care in Parkinson disease. Neurology, 2011; 77:851-857

Review by Marcia McCall

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The Other Side of Deep Brain Stimulation in PARKINSON’S DISEASE

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The Other Side of Deep Brain Stimulation in PARKINSON’S DISEASE

Deep Brain Stimulation (DBS) for PARKINSON’S DISEASE has now been a regular method of treatment for almost 25 years.  Improvements in technique and the appliances used have also come a long ways.  DBS has been used to treat symptoms that resist treatment with the available drugs with mostly excellent results.  But as the recipient’s age and the disease progresses, DBS can have some negative effects.

It is estimated that over 100,000 people with PARKINSON’S DISEASE all over the world have received DBS for treatment of motor symptoms of PD.  The results of long term follow up data are now becoming available.  Some patients have experienced significant and recurring infections that have greatly impacted their quality of life.  Often the infections stem from the generator device implanted under the skin on the chest.  Batteries die and generators need to be replaced and because of repeated replacements, infection is more of a risk. Some infections have been so severe that the entire device must be removed and the patient experiences worsening symptoms of PD.

As time passes, the disease progresses and the results of the DBS become less beneficial.  Cognitive decline in the patient and an inability to care for themselves properly make replacing the batteries or re-programming the generator difficult choices.  Family members and caregivers often have the burden to make these difficult decisions and often the best solution is the complete removal of the device.  This is not without a physical expense of worsening symptoms as well as the economic impact of the cost of more surgery.

Dystonia and dyskinesia that were once well controlled by the DBS worsen with the progression of the disease and the DBS can no longer be programmed to eliminate them. When patients reach this point, they have to be considered for nursing home care, especially if there are cognitive issues involved.  There have been cases where the device was completely removed and the patients experienced relief of the dystonia or dyskinesia and were able to return to their home with a great relief of the burden to return frequently for multiple battery replacements or adjustments to the spouse/caregiver.

DBS was a great replacement for the then popular lesioning of the subthalamic nucleus or globus pallidus.  Technologies have advanced, stereotactic and functional neurosurgeries have improved and lesioning may be an appropriate alternative, even after removal of the DBS device. While each carries certain risks and benefits, the benefit of pallidotomy on motor symptoms requires less exposure to the risk of infection than DBS.  Unilateral pallidotomy in patients who have had the DBS hardware removed, either for infections or cognitive decline, have shown good control of motor symptoms such as tremor, rigidity and dyskinesias.  Depending upon each individual’s specific situation, including symptoms, age, and ability to obtain long term care, the choice between DBS and pallidotomy should be considered.  In tight economic situations, or situations where long term follow up is not easily available lesioning of the globus pallidus might be a reasonable and efficacious treatment for some people with PARKINSON’S DISEASE.

 

Written by Marcia McCall

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SHORT NEWSWORTHY ITEMS

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Treating PD patients with their own cells

Eight PARKINSON’S DISEASE patients are waiting patiently for the Food and Drug Administration to give the final nod of approval to see if a new stem cell technology will help them.  Jeanne Loring from the Scripps Institute has collected cells from the skin of each of the patients and cultured them to grow into induced pluripotent stem cells, which she then induced to become dopamine producing neurons.  The new neurons will be transplanted into the brains of the patients from whom they were taken–an autologus transfer, which should not require doses of immunosuppressant’s.  If the new neurons begin making dopamine, then perhaps this will become a long-term treatment to slow the progress of PARKINSON’S DISEASE.  Animal studies are underway, and a meeting with the FDA is scheduled for January.

http:/www.utsandiego.com/news/2013/Mar/16/parkinsons-patients-induced-plurpotent-stem-cell/

 

Depression – cause, effect or just part of PARKINSON’S DISEASE

Albert Yang, M.D., Ph.D. a professor at the Taipei Veterans General Hospital in Taiwan has been working to understand the relationship between depression and PARKINSON’S DISEASE.  Studies show that depression often occurs before symptoms of PARKINSON’S, and about 40% of people with PARKINSON’S report depression and mood disorders. He and his colleagues analyzed the data from 4,634 people with depression and found that they were 3 times more likely to develop PARKINSON’S DISEASE than the control population that had not been depressed for at least 10 years.  He does not say that depression may cause PARKINSON’S, but rather that people who have depression that does not respond to usual treatment may require more aggressive treatment and more careful observation.

Psychiatric News, December 6, 2013: DOI:10.1176/appi.pn.2013.11b7

 

Just say “AHHH”

Dr. Max Little from the Parkinson’s Voice Initiative may have found a simple and unique way to help diagnose PARKINSON’S DISEASE.  He notes that people with PARKINSON’S not only develop stiffness, rigidity and tremor in their bodies, but also in their vocal cords that affects their speech production.  Using some sophisticated equipment and computer analysis, patients are asked to say “ahhh” and record their voice.  They results of these recordings have shown a 99% accuracy of prediction between healthy individuals and people with PARKINSON’S DISEAE.  The team of researchers is now working on using conventional and mobile telephones to record the “ahhhhs” and make an analysis.  If they are successful in their endeavors, there may be an economical and accurate early prediction of the disease.

www.dialoguewithdisability.blogspot.co.uk

 

Induced aging in cells may predict the future

A new method to study what happens in aging cells may help researchers better understand changes that occur in neurodegenerative diseases.  Scientists are able to take cells from the skin and culture them to become stem cells and then further inducing them to become neurons or other types of cells.  But induced pluripotent stem cells mature slowly, just as cells would normally mature.  To speed the process, the researchers added a protein called progerin and after a short exposure, the cells demonstrated the age related behaviors of old cells.

The team then took skin cells from people with PARKINSON’S DISEASE, cultured them into stem cells then engineered them to become the type of defective neuron found in PARKINSON’S brains.  They then exposed these neurons to progerin and watched them reproduce all the typical disease related symptoms, including mitochondrial defects, neuronal degeneration and cell death.  It was like observing PARKINSON’S DISEASE in a petri dish.

This technique may enable researchers to develop screening methods that could help predict the onset of PARKINSON’S DISEASE and also lead to early intervention to slow or even eliminate the progression by development of new drugs.

Miller et al. Human iPSC-based Modeling of Late-Onset Disease via Progerin-induced aging. Cell Stem Cell, December 2013

 

All reviews by Marcia McCall

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Novel Technique Reveals New Targets for PARKINSON’S DISEASE

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Novel Technique Reveals New Targets for PARKINSON’S DISEASE

Four genes that serve as “helper genes” to the parkin protein have been discovered using an innovative screening method.  The discovery of these genes will lead to more targets for research and development of potentially new drugs treatment of PARKINSON’S DISEASE.  The researchers from the National Institutes of Neurological Disorders (NINDS) and the National Center for Advancing Translational Sciences (NCATS) were recently published in the on-line journal, Nature.  

Parkin has long been studied and is known to be one agent that marks the damaged mitochondria for destruction.  Mitochondria are the tiny energy sources that cells depend on to function.  Normal parkin marks these damaged mitochondria for destruction and replacement but when the gene that codes for parkin protein becomes mutated, the damaged mitochondria build up and are not recycled, which causes even more damage to the cells.  This mitochondrial dysfunction is notable in PARKINSON’S DISEASE and other neurological movement disorders.

RNAi  (RNA interference) has been used since it was developed in 1998.  It has proven useful to researchers in understanding how genes function.  Using this technique, investigators inserted small interfering RNA (siRNA) into human cells, which enabled them to turn nearly 22,000 genes off.  They were then able to screen by automated microscopy exactly how each gene affected parkin’s ability to tag mitochondria that were damaged.  They found four such genes.

When they switched off two of those genes, parkin was unable to tag any damaged mitochondria.  When they switched off two other genes, parkin performed even better.  These genes are known to regulate proteins found in mitochondria.

Next, they developed a human nerve cell from an induced pluripotent cell from human skin.  They tested one of the genes, called TOMM7 on these cells and found that turning it off caused parkin to also stop tagging mitochondria.   After even more experiments, they are calling these four genes “helper genes” and hope that they will serve to develop new targets for better understanding of PARKINSON’S DISEASE and also for developing new drugs.  “We have discovered a network of genes that may regulate the disposal of dysfunctional mitochondria, opening the door to new drug targets for PARKINSON’S DISEASE and other disorders”, said Dr. Richard Youle, one of the researchers on this study.  His co-collaborator was Dr. Scott Martin.

Samuel A. Hasson, Lesley A. Kane, Koji Yamano, Chiu-Hui Huang, Danielle A. Sliter, Eugen Buehler, Chunxin Wang, Sabrina M. Heman-Ackah, Tara Hessa, Rajarshi Guha, Scott E. Martin, Richard J. Youle. High-content genome-wide RNAi screens identify regulators of parkin upstream of mitophagyNature, 2013; DOI: 10.1038/nature12748

 

Review by Marcia McCall

 

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