Using brain mapping to find Parkinson's disease treatment.

Chasing Breakthrough Cures for Parkinson’s Disease

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Summary: A disease-modifying drug for Parkinson’s disease remains the goal of researchers as they develop promising treatments using gene therapy, autophagy upregulators, and brain mapping. [Author: Brady Hartman. This article first appeared on LongevityFacts.]

Parkinson’s, Alzheimer’s and other forms of dementia are diseases of aging, and the incidence of these conditions rise with each passing year. Doctors expect these disorders to ramp up with increasing life expectancies.

Researchers aren’t just focusing on treatments for Alzheimer’s disease. Fortunately, scientists throughout the world are developing promising treatments for Parkinson’s disease as well.

Parkinson’s is a long-term degenerative disorder of the central nervous system. Named after the British doctor James Parkinson, who first described the condition in the early 1800’s, the disease afflicts about 1% of adults over the age of 60, and the incidence increases with each birthday. Males are affected more often than females.

Parkinson’s disease mainly affects the motor system by causing the death of the brain cells that secrete dopamine and are necessary for muscle movement. The symptoms generally come on slowly over time. Early in the disease, the most obvious symptoms are shaking, rigidity, slowness of movement, and difficulty in walking.

Parkinson’s disease significantly shortens lifespan. Following diagnosis, the average life expectancy is between 7 and 14 years.

No one knows what causes Parkinson’s, but scientists suspect genetic and environmental factors, such as pesticides and head injuries as a cause. People with an affected family member are more likely to get the disease themselves.

There is no known cure for Parkinson’s, which makes prevention especially important. Unfortunately, physicians can only treat the symptoms.

Origins of Parkinson’s Disease

Parkinson’s disease is characterized by the build-up of protein aggregates in the brain known as Lewy bodies. These protein clumps are similar to the amyloid plaques and tau protein tangles found in the brains of Alzheimer’s patients. Lewy bodies are thought to hamper brain function as they become misfolded and form aggregates. Brain researchers suspect that these plaques arise due to a cellular protective response and the real villains in Parkinson’s are the smaller, intermediate forms of the misfolded protein consisting of just a few molecules stuck together.

Brain researchers believe that the accumulation of misfolded proteins is due to the failure of the chaperone system, which uses helper molecules to coax proteins into the right position and shape. Parkinson’s is characterized by these plaques called a-synuclein protein aggregation. Damaged cellular components (macromolecular damage) combined with a  failure of the housekeeping service known as autophagy to remove these misfolded proteins worsen Parkinson’s disease.

Treatments for Parkinson’s Disease

The drug L-dopa is the standard-of-care drug for Parkinson’s disease and is used to treat movement symptoms, but unfortunately has side effects. Since 2000, researchers have trialed about 200 drugs for neurodegenerative conditions and about 99% have failed. The few successful drugs released help somewhat, do not radically alter the disease.

In the book ‘Juvenescence: Investing in the age of longevity‘, authors Jim Mellon and Al Chalabi give a good rundown of the treatments for Parkinson’s Disease, including those currently available and many in the pipeline. Mellon and Chalabi (M+C) give us an update on statins, cholinesterase inhibitors, autophagy upregulators and brain mapping.

 Statins and Parkinson’s Disease

Mellon and Chalabi report on recent research suggesting a link between statins and Parkinson’s saying that

“Until recently, it was thought that statins provided some protection against Parkinson’s, but research by Xuemei Huang of Penn State College of Medicine has disproved that. In fact, it seems that lipophilic statins, such as atorvastatin and fluvastatin, may actually increase the risk of Parkinson’s.”

Moreover, M+C report that researchers are trying a form of gene therapy by trialing the transplantation of pig brain cells into Parkinson’s patients, writing

“In addition, Living Cell Technologies has been engaged in promising research in implanting PiB (Pittsburgh compound B) brain cells from the pig’s choroid plexus into the brains of Parkinson’s patients using an alginate (seaweed-based) capsule to bypass immune reactions. The first four patients thus implanted are reported to be doing well, and have improved significantly in recognized cognitive tests.”

M+C also report that researchers are trying human embryonic stem cells on Parkinson’s patients, saying that

“Another 18 patients have recently been treated. In the Chinese city of Zhengzhou, Parkinson patients are being treated with human embryonic stem cells directly implanted into their brains.”

Promising Treatments for Parkinson’s Disease

Mellon and Chalabi report that researchers are trying a form of gene therapy by trialing the transplantation of fetal cells into Parkinson’s patients. M+C add that researchers at the Karolinska Institute in Sweden are

“reprogramming the brains of dopamine-deficient mice, using a virus carrying four genes to reprogram the astrocytes (the brain’s support cells) into dopamine-producing neurons. By the age of 60, approximately half of all dopaminergic cells have been lost in most people.”

Parkinson’s Disease and Autophagy

Scientists have long suspected that neurodegenerative diseases such as Parkinson’s are partially caused by the build-up of cellular debris due to a breakdown of the cellular housekeeping process known as autophagy.

Scientists are exploring upregulation of autophagy as a novel target for Parkinson’s drugs, say M+C. Autophagy upregulators use the mammalian target of rapamycin 1 (mTORC1) pathway as a channel for intervention. M+C add that the “removal of protein aggregates, which are toxic to the surrounding brain tissue, is a promising area of research.”

The loss of autophagy also plays a role in Alzheimer’s, and researchers have found that the drug rapamycin nearly prevents Alzheimer’s disease in mice, when given prophylactically.

Related article: British researchers discover a key to the collapse in cellular housekeeping that leads to Alzheimer’s and Parkinson’s

Brain Mapping Aids Search for Parkinson’s Treatment

Brain mapping works very much like the way a technician troubleshoots a piece of electronics that isn’t working. To troubleshoot the problem in electronics often involves probing the flow of electricity through the various components of the circuitry to locate any faulty parts.

Brain mapping works along the same lines and is a collection of neuroscience techniques that map biological properties onto spatial representations of the human brain to create maps.

Coffee Reduces Parkinson’s Disease

Large observational studies have found that coffee and tea drinkers have a reduced risk of developing Parkinson’s and Alzheimer’s.

The authors of a large systematic review reported that individuals who drank three cups of coffee daily had a 29% lower risk of Parkinson’s disease. The authors added that more is not necessarily better and consuming five cups didn’t seem to add an extra benefit.

Caffeine appears to be the active ingredient in the brain health benefit of coffee. Caffeine has been shown to elevate levels of granulocyte-colong stimulating factor (G-CSF), a growth factor thought to improve memory and brain health. G-CSF promotes the formation of new brain cells and encourages new synaptic connections between them.

Bottom Line

Scientists continue to search for treatments that do more than just alleviate symptoms, and instead are searching for a disease-modifying agent for Parkinson’s, what M+C describe as the “holy grail of pharmacological intervention in neurodegenerative disease.” M+C add that this “holy grail” of Parkinson’s disease treatments is “still some way off.”

Hopefully, the continued work of researchers and scientists will yield more effective therapies in the future.

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References

Cover photo: Brain mapping to find a cure for Parkinson’s, Alzheimer’s and other forms of dementia. Credit: Human Connectome Project, NIH.

Jim Mellon, Al Chalabi. Juvenescence: Investing in the age of longevity. 1st Edition. Harriman House. ISBN(s): 9780993047817 – 9780993047824, 25th Sep 2017. Link.

Disclaimer

Diagnosis, Treatment, and Advice:  This article is intended for educational and informational purposes only and is not a substitute for qualified, professional medical advice.  The information and opinions provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. Consult a qualified and licensed physician for the diagnosis and treatment of any and all medical conditions. Experimental therapies for Parkinson’s disease carry a much higher risk than FDA-approved ones. Call 911, or an equivalent emergency hotline number, for all medical emergencies. As well, consult a licensed, qualified physician before changing your diet, supplement or exercise programs.
Photos, Endorsements, & External Links:  This article is not intended to endorse organizations, companies, or their products. Links to external websites, mention or depiction of company names or brands, are intended for illustration only and do not constitute endorsements.

7 Replies to “Chasing Breakthrough Cures for Parkinson’s Disease”

  1. Alan Green M.D.

    Of drugs available today most promising to stop Parkison’s disease at cellular level is rapamycin See:
    “Mitochondral quality control via the PGC1a-TFEB signaling Pathway is compromised by Parkin Q311X mutation but independently restored by RAPAMYCIN, Siddiqui. 2015 (from Buck Institute) and “RAPAMYCIN protects against neuron death in in vitro and in vivo models of parkinson Disease” Cristina Malagelada, 2010.

    Problem: Rapamycin is generic drug so don’t ever expect to see human clinical trials.

  2. Adam Lallana

    My sister was diagnosed months ago after several years of being told she had “restless leg syndrome.” She has very bad toe cramps, where here foot looks like a claw and is very painful. She was also “freezes” on trying to stand from a sitting position. She speaks so quickly and “gabbles” that we are unable to decipher what she is saying.

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