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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Link Between Pesticides and Parkinson’s Disease Identified

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Link Between Pesticides and Parkinson’s Disease Identified

Pesticides have long been thought to be involved in the pathology of PARKINSON’S DISEASE, but finding a definite link has been a near impossibility.  Many researchers spending many years of research sought to find this elusive relationship, and their primary theory has finally proven correct.  But it took some very advanced, newly developed technological research skills and two major teams of researchers to unlock the clues.

Past studies had shown there were increased risks to certain populations, such as farmers and others who were exposed to pesticides; however there were always people who never showed any response to their exposure.  Why were some folks more likely to develop PARKINSON’S DISEASE while others did not?  As the relatively new studies of genetics have advanced, the connection between genes and pesticides became clear.

Researchers at the Burnham Institute in La Jolla, California together with another team from the Whitehead Institute of the Massachusetts Institute of Technology in Cambridge, MA. used skin cells collected from people with PARKINSON’S DISEASE that carried the genetic mutation for alpha synuclein, the signature protein found in Lewy bodies.  From these skin cells, they induced human pluripotent stem cells to grow.  Pluripotent stem cells are able to develop into various specific types of cells when properly stimulated.  In the cells that they grew, they removed the genetic mutation for alpha synuclein in half of them and left it in the others.  They then programmed the cells to grow into the dopamine containing neurons found in PARKINSON’S DISEASE and began exposing both sets to various pesticides in varying amounts.

When they began to study the results of these exposures, the cells that carried the genetic mutation for alpha synuclein became damaged and cell death soon followed.  Those without the mutation survived.  So they started looking closer and found that in the cells with the genetic mutation, a vital mitochondrial pathway that protects cells with dopamine was interrupted, causing the cells to die.  In the non mutation carrying cells, this pathway would protect the cells and keep them alive and functional.

This study has shown beyond a doubt the relationship between the environment and a person’s genetics.  But while it has found one channel affecting dopamine neurons, this does not rule out that there may be many other mutations or pathways that could also be affected. Stuart Lipton, one of the lead researchers on this project says: “In the future, we anticipate using the knowledge of mutations that predispose an individual to these disease in order to predict who should avoid a particular environmental exposure.  Moreover, we will be able to screen for patients who may benefit from a specific therapy that can prevent, treat or possibly cure these diseases.”

Not being content merely to identify the problem, another principal investigator on this study decided to search for a solution to the problem.  Rajesh Ambasudhan explains:  “Once we understood the pathway and the molecules that were altered by the pesticides, we used high-throughput screening to identify molecules that could inhibit the effect…  One molecule we identified was isoxazole, which protected mutant neurons from cell death induced by the tested pesticides.”  This molecule is currently used in other drugs already approved by the Food and Drug Administration, so it may be possible to quickly find a way to repurpose these medications to provide an early treatment for Parkinson’s disease.

.

Cell, November 27, 2013; NIH, P01 HD29587, P01 ES016738, and P30 NS076411, R37 CA084198

“Isogenic human iPSC Parkinson’s model shows nitrosative stress-induced dysfunction in MEF2-PGC1a transcription”

Cell, December 5, 2013.

Scott D. Ryan (1,*) Nima Dolatabadi (1,*), Shing Fai Chan (1), Xiaofei Zhang (1), Mohd Waseem Akhtar (1), James Parker (1), Frank Soldner (2), Carmen R. Sunico (1), Saumya Nagar (1), Maria Talantova (1), Brian Lee (1), Kevin Lopez (1), Anthony Nutter (1), Bing Shan (3), Elena Molokanova (1), Yaoyang Zhang (3), Xuemei Han (3), Tomohiro Nakamura (1), Eliezer Masliah (5), John R. Yates III (3), Nobuki Nakanishi (1), Aleksander Y. Andreyev (4), Shu-ichi Okamoto (1), Rudolf Jaenisch (2), Rajesh Ambasudhan (1), and Stuart A. Lipton (1,5).

 

Review by Marcia McCall

 

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One Mutated Gene Causes Multiple Neurodegenerative Disorders

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One Mutated Gene Causes Multiple Neurodegenerative Disorders

A single mutated gene targets cells in the basal ganglia and disrupts the cells’ abilities to function normally.  The gene, HPRT short for Hypoxanthine Guanine Phosphoribosyltransferase,, is considered a “housekeeping gene”, responsible for cellular maintenance and repair. When it is mutated, it affects the neurotransmitter dopamine and dopamine neurons and results in many neurological diseases including Alzheimer’s, PARKINSON’S DISEASE, Lesch-Nyhan, and Huntington’s disease.

Researchers on the study team lead by Theodore Friedmann, M.D., professor of pediatrics at the University of California, San Diego conducted a gene expression study using mouse embryonic stem cells modified to be lacking in HPRT. They found that when HPRT is deficient cells do not develop normally; although they appear as neurons, their functions are impaired.  Some of the impaired functions observed were with cell cycles and replication, RNA metabolism, DNA damage and repair as well as cell signaling.

Results of this study provide preliminary results, showing how a defect in this gene leads to the cellular defects found in many neurological diseases.  Research can now look for ways to target HPRT genetic mutation possibly leading to specific treatments.  It is one of many pathways in the development of neurological disease; the task of future research lies in finding ways to better understand these pathways.

Tae Hyuk Kang, Yongjin Park, Joel S. Bader, Theodore Friedmann. The Housekeeping Gene Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) Regulates Multiple Developmental and Metabolic Pathways of Murine Embryonic Stem Cell Neuronal Differentiation.PLoS ONE, 2013; 8 (10): e74967 DOI:10.1371/journal.pone.0074967

 

reviewed by Marcia McCall

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Walking Speed and PARKINSON’S DISEASE

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Walking Speed and PARKINSON’S DISEASE

Researchers at the University of Michigan headed by Nicolaas Bohnen have found that the speed of walking in PARKINSON’S DISEASE depends not only on lack of dopamine but can also be affected by lack of acetylcholine.  This suggests that “the clinical heterogeneity of PARKINSON’S DISEASE results from variable involvement of different brain systems”, according to Dr. Bohnen.

In a study that involved 125 subjects with PARKINSON’S DISEASE, they found 38 of them lacked acetylcholine in addition to lack of dopamine.  When they compared the speed of walking to a control group of 32 non-Parkinsonian subjects, they found the group lacking dopamine walked only slightly slower than the control group.  The speed of the group lacking both acetylcholine and dopamine was markedly slower.

They also compared cognitive function in relation to speed of walking and found that the lack of acetylcholine “may reflect the impact of impaired cognitive processing during ambulation.”  The cognitive scores of subjects with lack of acetylcholine and dopamine were lower than those with lack of dopamine only, but non Parkinsonian subjects scored higher than both groups of subjects with PARKINSON’S DISEASE.

The results of this study indicate that people with PARKINSON’S DISEASE whose problems with walking speed do not improve on dopamine replacement therapy may have a form of PARKINSON’S DISEASE that is a multisystem neurodegenerative disorder.

Nicolaas I. Bohnen, MD, PhD, Kirk A. Frey, MD, PhD, Stephanie Studenski, MD, MPH, Vikas Kotagal, MD, Robert A. Koeppe, PhD, Peter J.H. Scott, PhD, Roger L. Albin, MD Martijn L.T.M. Müller, PhD;Gait speed in Parkinson disease correlates with cholinergic degeneration  Published online before print September 27, 2013, doi: 10.1212/WNL.0b013e3182a9f558Neurology 10.1212/WNL.0b013e3182a9f558

 

review by Marcia McCall

 

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