200 years later, the search for a cure for Parkinson’s continues

On the surface, actor Michael J. Fox, singer Neil Diamond, civil rights activist Jesse Jackson and Scottish comedian Billy Connolly would appear to have little in common. Except for one thing. They all have Parkinson’s Disease (PD).

Their celebrity status has helped raise public awareness about the condition, but studies show that awareness doesn’t amount to an understanding of PD or the extent to which it impacts someone’s life. In fact a study in the UK found that many people still don’t think PD is a serious condition.

To try and help change that people around the world will be holding events today, April 11th, World Parkinson’s Day.

The disease was first described by James Parkinson in 1817 in “An Essay on the Shaking Palsy”. In the essay Parkinson described a pattern of trembling in the hands and fingers, slower movement and loss of balance. Our knowledge about the disease has advanced in the last 200 years and now there are treatments that can help slow down the progression of the disease. But those treatments only last for a while, and so there is a real need for new treatments.  

That’s what Jun Takahashi’s team at Kyoto University in Japan hope to provide. In a first-of-its-kind procedure they took skin cells from a healthy donor and reprogrammed them to become induced pluripotent stem cells (iPSCs), or stem cells that become any type of cell. These iPSCs were then turned into the precursors of dopamine-producing neurons, the cells destroyed by PD, and implanted into 12 brain regions known to be hotspots for dopamine production.

The procedure was carried out in October and the patient, a male in his 50s, is still healthy. If his symptoms continue to improve and he doesn’t experience any bad side effects, he will receive a second dose of dopamine-producing stem cells. Six other patients are scheduled to receive this same treatment.

Earlier tests in monkeys showed that the implanted stem cells improved Parkinson’s symptoms without causing any serious side effects.

Dompaminergic neurons derived from stem cells

Scientists at UC San Francisco are trying a different approach, using gene therapy to tackle one of the most widely recognized symptoms of PD, muscle movement.

In the study, published in the journal Annals of Neurology, the team used an inactive virus to deliver a gene to boost production of dopamine in the brain. In a Phase 1 clinical trial 15 patients, whose medication was no longer able to fully control their movement disorder, were treated with this approach. Not only were they able to reduce their medication – up to 42 percent in some cases – the medication they did take lasted longer before causing dyskinesia, an involuntary muscle movement that is a common side effect of the PD medication.

In a news article Dr. Chad Christine, the first author of the study, says this approach may also help reduce other symptoms.

“Since many patients were able to substantially reduce the amount of Parkinson’s medications, this gene therapy treatment may also help patients by reducing dose-dependent side effects, such as sleepiness and nausea.” 

At CIRM we have a long history of funding research into PD. Over the years we have invested more than $55 million to try and develop new treatments for the disease.

In June 2018, the CIRM Board awarded $5.8 million to UC San Francisco’s Krystof Bankiewicz and Cedars-Sinai’s Clive Svendsen. They are using neural progenitor cells, which have the ability to multiply and turn into other kinds of brain cells, and engineering them to express the growth factor GDNF which is known to protect the cells damaged in PD. The hope is that when transplanted into the brain of someone with PD, it will help slow down, or even halt the progression of the disease. 

The CIRM funding will hopefully help the team do the pre-clinical research needed to get the FDA’s go-ahead to test this approach in a clinical trial. 

David Higgins, CIRM Board member and Patient Advocate for Parkinson’s Disease

At the time of the award David Higgins, PhD, the CIRM Board Patient Advocate for Parkinson’s Disease, said: “One of the big frustrations for people with Parkinson’s, and their families and loved ones, is that existing therapies only address the symptoms and do little to slow down or even reverse the progress of the disease. That’s why it’s important to support any project that has the potential to address Parkinson’s at a much deeper, longer-lasting level.”

But we don’t just fund the research, we try to bring the scientific community together to help identify obstacles and overcome them. In March of 2013, in collaboration with the Center for Regenerative Medicine (CRM) of the National Institutes of Health (NIH), we held a two-day workshop on cell therapies for Parkinson’s Disease. The experts outlined the steps needed to help bring the most promising research to patients.

Around one million Americans are currently living with Parkinson’s Disease. Worldwide the number is more than ten million. Those numbers are only expected to increase as the population ages. There is clearly a huge need to develop new treatments and, hopefully one day, a cure.

Till then days like April 11th will be an opportunity to remind ourselves why this work is so important.

Two National Parkinson’s Disease Organizations Join Forces

David Higgins, Parkinson's advocate and CIRM Board member

David Higgins, Parkinson’s advocate and CIRM Board member

Guest blogger David R. Higgins, PhD, is a Parkinson’s Patient Advocate and a CIRM ICOC board member.

Two national Parkinson’s organizations have decided to join forces: The Parkinson’s Action Network (PAN) will be integrated into The Michael J. Fox Foundation (MJFF). Both have served the Parkinson’s community in separate and important ways, but as MJFF CEO Todd Sherer said in a joint press release, “Working as a single entity, MJFF and PAN will bring the passion and commitment of our joint community to bear on articulating and advancing key public policy priorities affecting millions of PD patients and families.”

Michael J. Fox Foundationmjff_vert_rgb_logo_300

Best known for its namesake founder and mission to fund Parkinson’s research, MJFF has awarded more than $450 million to fund Parkinson’s research. MJFF has distinguished itself as a fundraising giant and has kept their eye on their goal of funding high-quality PD research always with the goal of a cure in mind. In addition to funding research, the MJFF is known for its database of Parkinson’s related clinical trials, which it vets and makes available to anyone interested through a system that works a lot like a matchmaking service (i.e. the right trial for the right person based on personal preferences and interests). To learn more about the MJFF follow the link: https://www.michaeljfox.org.

Parkinson’s Action Networksite-header2

PAN has been a Washington, DC-based organization created to be a single voice for a united Parkinson’s community, with a proven track record for effective advocacy for federal legislation and policy that considers the needs of the Parkinson’s community. We used to call this “lobbying”, now we call it “advocacy”. To learn more about PAN follow the link: http://parkinsonsaction.org.

One + One = ThreePAN-MJFF-homepage-img

Integration of PAN into MJFF creates a Parkinson’s patient advocacy trifecta that brings together the strengths of each organization: patient care (access, knowledge, education), research support (fundraising to support research, new therapies and ultimately a cure) and political action (legislation and public policy supporting the Parkinson’s community).

The merged organization will have two groups of advisors, the Unified Parkinson’s Advocacy Council, which will maintain a single voice for advocacy, and a Public Policy Council, which will provide guidance and advice on policy strategies that are important to the Parkinson’s community. While MJFF will continue to be based in NYC, for the first time they will also have an office in Washington, DC. You can read more about the merge here.

PAN and CIRM Have Common Roots

As it turns out there is a strong connection between PAN and CIRM. California attorney and Parkinson’s patient Joan Samuelson founded PAN in 1991. Samuelson described her “surge of excitement” in 1990 when she read about a possible breakthrough in Parkinson’s therapies that used tissue transplants, and how that hope was “swept away” when she read about a federal policy banning any federal support for such research.

PAN was Samuelson’s brainchild and reflected her prescient vision that it would take a political effort at the national level to counter this anti-tissue transplant movement. PAN became famous for its national network of grassroots organizers who could muster thousands of calls to Congress with a day’s notice to voice support or opposition to legislation.

It should come as no surprise that Samuelson was a supporter of California’s Proposition 71 that voters approved in 2004, creating CIRM. Samuelson became CIRM’s first Parkinson Patient Advocate and served in that role until 2014. She was a famously outspoken member of the ICOC (CIRM’s governing Board) and supporter of the Parkinson’s community.

I am humbled to be the one to follow her as the Parkinson’s Patient Advocate on the ICOC, but have no illusions that Samuelson didn’t just leave “big” shoes behind to fill, she left behind shoes so big a family of four could live in them! Samuelson lives in retirement in Sonoma County, CA. I met her once, but never knew her other than by reputation. Words I have heard used to describe her include character, integrity, brilliance, tenacity and one who conveys a sense of urgency for making the world a better place for Parkinson’s patients.

Today, there is not yet a cure, but there is plenty of hope.


 

Notes on Parkinson’s disease

Parkinson’s disease (PD) is a progressive disease that affects the nervous system and for which there is no cure. Over a million people in the US are known to have this debilitating disease. PD is a type of movement disorder, characterized by so-called motor symptoms including too little, too much, or inappropriate movements of the body. Motor symptoms are attributed to the death of specialized cells in a part of the brain that controls movement. These cells produce dopamine, a chemical that allows these specialized nerve cells to “talk” to each other and thus direct movement. What causes these cells to die is an active area of research, including CIRM-funded research. Our understanding of PD has gotten more sophisticated and we now understand that in addition to motor symptoms there are so-called non-motor symptoms. Non-motor symptoms include severe fatigue, insomnia, depression, anxiety, mild cognitive impairment and dementia among others. PD patients often report that non-motor symptoms impact the quality of their lives more than motor symptoms.