Over the last year, three promising new treatments for symptoms of Parkinson’s became available in the United States, but progress has been less hopeful on the development of drugs to modify the progression the disease, according to researchers who spoke at an annual movement disorders conference in San Diego last month.<img loading="lazy" decoding="async" class="alignright size-medium wp-image-22380" src="https://blog-api.23andme.com/wp-content/uploads/2015/03/paul-300x235.jpg" alt="paul" width="300" height="235" srcset="https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2015/03/paul-300x235.jpg 300w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2015/03/paul-768x602.jpg 768w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2015/03/paul-1024x802.jpg 1024w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2015/03/paul-880x689.jpg 880w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2015/03/paul-1180x924.jpg 1180w, https://blog.pub.us-west-2.prd.23andme.us/wp-content/uploads/2015/03/paul.jpg 2016w" sizes="auto, (max-width: 300px) 100vw, 300px" />
<a href="https://blog.23andme.com/23andme-research/22378/">23andMe’s Paul Cannon</a>, PhD, who serves as the manager for our <a href="https://www.23andme.com/pd/">Parkinson’s Research Community</a>, was among the thousands of attendees at the massive 19th International Congress of Parkinson’s Disease and Movement Disorders in San Diego. The four-day event attracts scientists, clinicians and medical professionals from around the world, giving them an opportunity to share the latest treatments and the newest research into Parkinson’s disease.


“In terms of treatments for Parkinson’s it was a mixed bag,” said Paul.
While new options for the treatment of symptoms in the form of gels, skin patches, intestinal pumps,<a href="http://www.mdscongress2015.org/Congress-2015/Press/News-Releases/260-Inhaled-Levodopa.htm"> inhalers</a> and even<a href="http://webcache.googleusercontent.com/search?q=cache:WZ8TqAwG5C4J:www.mdscongress2015.org/Congress-2015-Files/pdfs/2015LateBreakingAbstractsPubDoc.pdf+&#038;cd=2&#038;hl=en&#038;ct=clnk&#038;gl=us"> deep brain stimulation</a>, offer Parkinson’s patients new ways for quickly treating certain symptoms, Paul noted that researchers also reported some setbacks in the development of other treatments that many had hoped could slow the progress of the disease. The use of gels, skin patches, pumps and inhalers are used for better delivery of the drugs levodopa and carbidopa, which effectively treat motor function symptoms for Parkinson’s patients. Paul said there is also some interesting clinical studies around non-levodopa drugs such as safinamide and rivastigmine, but there was little new to report around treatment for the progression of the disease.
“In terms of disease modifying therapies it was a much less successful year,” Paul said.


Probably the most notable setback in the drug development pipeline was the news around the<a href="http://jama.jamanetwork.com/article.aspx?articleid=2108890"> halt of a late stage study of creatinine</a>, an amino acid that researchers thought could help protect nerve cells in Parkinson’s patients. But the study was stopped because interim data showed the treatment didn’t help patients any differently than those treated with a placebo. Another disappointment was around the<a href="http://www.thelancet.com/journals/laneur/article/PIIS1474-4422%2815%2900144-1/abstract"> failure of the drug pioglitazone</a>. In Paul’s assessment of the study for pioglitazone, there was some indication from biomarkers that the drug could still hold benefits if used at a different doses.
But in his time at the conference Paul said there were several presentations that indicate there are also some studies currently in the drug development pipeline. He singled out three that are either in phase three development or about to start – studies into the drugs<a href="https://clinicaltrials.gov/ct2/show/NCT02168842"> isradipine</a>,<a href="https://www.michaeljfox.org/foundation/grant-detail.php?grant_id=403"> inosine</a> and<a href="https://www.michaeljfox.org/foundation/grant-detail.php?grant_id=1124"> exanatide</a>.
Others therapies to pay attention to, according to Paul, are two in early development that target alpha-synuclein – an antibody from the drug company Prothena, and a vaccine from Affiris.
If you’ve paid much attention to research into Parkinson’s you’ll know that a lot of focus has been on the role alpha-synuclein plays not just in Parkinson’s but also other neurodegenerative disorders. Alpha-synuclein is a protein that is primarily found in brain tissue. In Parkinson’s patients this protein clumps together in the brain. Warren Olanow, an MD and professor of neuroscience at Mount Sinai, discussed some of theories on the best therapeutic approaches to deal with this from using antibody based treatments to systems of either blocking the clumping or reducing the gene expression of alpha-synuclein.


Working at 23andMe, where our researchers have done several genome wide association studies that helped uncover new genetic associations with Parkinson’s, Paul said he was struck by some of the information presented by Andy Singleton, of the National Institutes of Health. Although studies indicate that as much as 30 percent of the risk for the most common type of Parkinson’s is genetic, the genetic variants found so far account for only about five percent of that risk. Even though genome wide association studies were used to discover 28 known variants associated with Parkinson’s disease, Singleton favors the use of whole genome sequencing as a better approach to find the remaining genetic variants. (23andMe is working on a multi-year study with Genentech to sequence 3,000 Parkinson’s patients to learn about the genetic underpinnings of the disease.)


In another promising presentation, the researcher Haydeh Payami, PhD at UC Berkeley and a joint faculty member at the<a href="http://hudsonalpha.org/research/faculty-and-projects/faculty-profiles"> HudsonAlpha Institute</a>, reported on a nice example of gene environment interaction, Paul said. Looking at caffeine consumption and genetic risk, Payami’s research found that drinking coffee in general can reduce one’s risk for Parkinson’s by 30 percent. But for individuals with certain genotypes in two genes – GRIN2A and MAPK10 – caffeine consumption did little to reduce their risk for Parkinson’s. Yet when Payami looked at the 7 percent of individuals who had the less common genotypes in both of those genes coffee consumption was “highly protective.”


“In summary whilst lack of progress in the clinic is disappointing, continued insights into the underlying disease mechanisms from genetics and other routes of investigation, gives hope that we will see an increasing number of rationally targeted therapies being tested in well designed studies,” Paul said of what he learned at the conference. “Resources such as 23andMe Parkinson’s Research Community are a key part of this on-going research effort.”
<img loading="lazy" decoding="async" class="aligncenter wp-image-22634 size-large" src="https://blog-api.23andme.com/wp-content/uploads/2015/06/Parkinsons-Research-Community-640x238.jpg" alt="Parkinson's Research Community" width="640" height="238" />

Research Update on Parkinson’s Disease

Things aren’t always as they seem with Parkinson’s disease with one recent study showing as many as half those diagnosed with the disease don’t have it, according Dr. J. William Langston.<img loading="lazy" decoding="async" class="alignright size-medium wp-image-12362" src="https://blog-api.23andme.com/wp-content/uploads/2012/04/Langston-252x300.jpg" alt="Langston" width="252" height="300" />
At a recent visit to 23andMe, Langston, a pioneering Parkinson’s researcher as well as the founder and chief science officer of the <a href="http://www.thepi.org/" target="_blank" rel="noopener noreferrer">Parkinson’s Institute</a>, gave a quick overview not just of the challenges around diagnosing the disease but also some of the more hopeful recent findings.
Both a friend of 23andMe and a scientific advisor for 23andMe’s <a href="https://www.23andme.com/pd/#section4" target="_blank" rel="noopener noreferrer">Parkinson’s research community</a>, Langston’s presentation offered scientists here a quick overview of the shifting understanding of Parkinson’s.
The traditional view is that Parkinson’s is a movement disorder triggered by a loss of dopamine containing neurons in the substantia nigra, a particular region of the brainstem. But because diagnosis is so difficult, sometimes people with Parkinson’s-like symptoms are misdiagnosed with the disease itself.
In truth, a definitive diagnosis for the disease requires a post-mortem examination to confirm the presence of abnormal protein deposits in the brainstem called “Lewy bodies.” These clumps are loaded with a protein called alpha-synuclein. One promising development in the effort for diagnosis are new techniques for detecting alpha-synuclein, and related structures known as neurites. What’s also been interesting is that scientists have found alpha-synuclein deposits not just in the brainstem, but in other regions of the brain as well as the gut and heart. These same regions may be associated with non-motor symptoms that Parkinson’s patients deal with including such things as a change in their sense of smell, constipation or sleep disturbances.
Like many diseases, the earlier it is diagnosed the better the outcome for patients. Even though there is no cure for Parkinson’s there are treatments and interventions that can manage some of the symptoms and help patients maintain their quality of life. But diagnosis – especially early on – is very poor.
To illustrate that point, Langston, who has been a long time scientific adviser to 23andMe Parkinson’s research community, cited a recent study showing about half of the cases were misdiagnosed. The study was of patients who’d died within five years of being diagnosed with Parkinson’s, but autopsies of the patients revealed that about 50 percent didn’t have the disease. This has enormous implications for research especially clinical trials of disease modifying therapies, which need to recruit patients early in the disease process.
An extensive review of Parkinson’s disease genetics that Langston and his collaborators recently submitted for publication suggests that this confusion is not limited to clinical diagnosis. Looking at 31 different genetic markers associated with inherited Parkinson’s, his team found that only three have been shown to also be associated with the classic pathological features of Parkinson’s. In addition, researchers have found in doing autopsy on patients that even those who share the same genetic marker (one associated with Parkinson’s disease) the kind of protein bodies found in their tissue and where they are found, can be very different.
To try and manage this confusing situation Langston and his colleagues proposed the name  Multisystem Lewy Body Disease (brain, spinal cord and peripheral autonomic nervous system) to better reflect what the researchers have found.
Despite all of this, Langston said that there are promising new diagnostic and treatment tools currently in development.

Parkinson’s Research Challenges

At an annual conference last month sponsored by the Michael J. Fox <img loading="lazy" decoding="async" src="https://blog-api.23andme.com/wp-content/uploads/2009/03/parkinsonsdisease.jpg" alt="parkinsonsdisease" class="alignright size-full wp-image-3133" width="260" height="236" />Foundation, scientists, academics and business representatives gathered in New York City to explore some of the latest and most promising Parkinson’s research that’s being supported by the foundation.
23andMe’s Paul Cannon, who manages our Parkinson’s Research Community, was among the more than 250 people gathered to learn more about some of the newest findings meant to help us better understand the biology of the disease as well as potential new targeted therapies.


Below is some of what caught Paul’s attention. The Michael J. Fox Foundation, which has also been a big supporter of <a href="https://www.23andme.com/pd/" target="_blank" rel="noopener noreferrer">23andMe&#8217;s Parkinson&#8217;s Research Community</a>, also recently posted a blog about the conference <a href="https://www.michaeljfox.org/foundation/news-detail.php?latest-in-parkinson-research-showcased-at-mjff-conference" target="_blank" rel="noopener noreferrer">here</a>. 


<h6>
Alpha-Synuclein</h6>

One of the interesting new disease modifying drugs is a vaccine that targets a protein called <a href="https://www.michaeljfox.org/understanding-parkinsons/living-with-pd/topic.php?alpha-synuclein" target="_blank" rel="noopener noreferrer">alpha-synuclein</a>. We’ve <a href="https://blog.23andme.com/news/the-state-of-the-science-of-parkinsons-research/" target="_blank" rel="noopener noreferrer">written in the past</a> about research on alpha-synuclein. This protein is encoded in the SNCA gene and found in the brain. Researchers discovered that these proteins accumulate and clump together in people with Parkinson’s. The thought is that removing these “sticky proteins” could help slow or stop the progression of Parkinson’s.
In an early stage clinical study the vaccine was given to about two-dozen patients. A little more than half of the patients who received the vaccine showed an antibody response. At this stage it’s unclear why some patients responded to the vaccine and others didn’t. Importantly the vaccine appears to be safe and well tolerated and future studies will address the reason for this differential response as well as ask whether the treatment has any effect on the symptoms and progression of Parkinson’s.
 
<h6>DPP-4 Inhibitors</h6>

Recently evidence has emerged that certain type of drugs used to treat type 2 diabetes may hold promise for treatment of Parkinson’s patients as well. Encouraging preclinical data were presented for one class of drugs called dipeptidyl protease-4 (DPP-4) inhibitors. It is not known how these drugs might work to affect Parkinson’s, but their use to in diabetics has shown them to be safe which will make it easier to carry out clinical studies in PD. 
 
<h6>Levodopa Carbidopa</h6>

Whilst disease modifying therapies are understandably of great interest, there is still a lot of room for improvement with current treatments. An example of this is a system designed to deliver a continuous level of a popular drug cocktail used for Parkinson’s patients called levodopa carbidopa.
A liquid form of the drug combo was developed and clinical studies showed that when used with either a pump or a patch it resulted in more consistent levels of the drugs in patients’ blood. This should result in better control of symptoms and it is hoped that it will also decrease the development of uncontrolled movements, known as dyskinesias, associated with long term use of levodopa.


Looking to the Future
These were just some of the highlights from Paul’s notes, but it doesn’t begin to cover the value in bringing together so many researchers working on Parkinson’s.
It also highlights the value of 23andMe’s long time collaboration with the Michael J. Fox Foundation in research. In partnership with our Parkinson’s disease research community we continue to focus on understanding the relationship between the environment and genetic factors in the development of the disease, discovering how and why those with Parkinson’s react differently to existing treatments, as well accelerating the discovery and development of new treatments.

alpha-synuclein

Research Update on Parkinson’s Disease

Parkinson’s Research Challenges

Highlights on New Parkinson’s Research

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