Parkinson’s Patient Brings Awareness to Mannitol Supplement in New Documentary

mannitol documentary

A documentary premiering July 29 on Israel’s satellite TV service provider, yes, highlights what one Parkinson’s disease patient was able to achieve when he set out to advocate for himself and other patients. 

In collaboration with Nisan Katz and Nir Kafri Productions, “My Disease Our Revolution” follows Dany Vesely, 63, as he champions a supplement that he says helped him combat his Parkinson’s.  

At the center of the story is an over-the-counter sweetener called mannitol. Due to the efforts of Vesely and others, the supplement now is being tested in Parkinson’s patients in a small randomized, controlled Phase 2a trial. But the real story is not necessarily in the trial or its eventual results; it’s how it got there in the first place.

The documentary crew followed Vesely for the past two years, filming him as he and his business partner gained support for a new venture, CliniCrowd, which is exploring the idea of using patient-reported data to test the viability of readily available supplements.

These are compounds that have been deemed safe by the U.S. Food and Drug Administration (FDA) and have shown promise in research for some diseases, but for which companies have little financial incentive to put through expensive clinical trials. 

Dany Vesely on a hike in Israel. (Photo by Nir Kafri)

“Bringing back the power to the patient, it can be a change; it can be a revolution,” filmmaker Katz told Parkinson’s News Today in a video interview.  

In the documentary, Vesely and Sagit Weiss, a physician and immunologist and Parkinson’s patient, both said mannitol helped stabilize their symptoms after consistently taking the water-soluble supplement, which also is used as a healthier alternative to sugar. Vesely’s success with mannitol was the inspiration to form CliniCrowd and let patients find out for themselves. 

“We couldn’t stay calm to the fact that 10 million patients around the world will not have the chance to know about it,” Vesely said in a video interview.

From diagnosis to startup

Vesely, diagnosed with Parkinson’s in 2013, didn’t know what mannitol was until his friend had a chance meeting with a PhD researcher who had been studying small molecules that could inhibit a protein responsible for the disease.

That researcher’s name was Daniel Segal, PhD, a geneticist at Tel Aviv University. Segal published a paper (incidentally, the same year Vesely was diagnosed), which suggested that mannitol could “promote [alpha]-synuclein clearance in the cell bodies” as seen in fruit fly and mouse models. For an unknown reason, alpha-synuclein forms toxic clumps that impair the production of dopamine, leading to Parkinson’s. 

Read more about the science behind mannitol and its potential in Parkinson’s here.

“I think it will be interesting for Parkinson’s patients not only about the mannitol,” Katz said. “I think it’s also about the way Dany copes and fights the disease.” 

Parkinson’s is a progressive, visible disease. It causes involuntary tremors, slowed movement, rigidity or stiffness, and impaired balance. Less visible are sleep problems, constipation, slurred speech, and mood disorders.

Katz opens the film with Vesely slowly getting out of bed, shuffling to the bathroom to brush his teeth. The documentary also shows him riding his stationary bicycle and working on his balance in a dance class.

Dany Vesely does one of his exercises in a screenshot of the documentary. (Photo by Nir Kafri)

“A lot of people are getting Parkinson’s and becoming very lonely and they’re inside themselves, and they are crying, ‘why did we get Parkinson’s’?” Amir Sadeh, a friend of Vesely’s and CEO and co-founder of CliniCrowd, who also started taking mannitol as a preventive measure, said in a video interview. “Not Dany, he’s a fighter. ‘With my Parkinson’s, I’m going to help the world.’” 

Sadeh and Vesely, along with three others, founded CliniCrowd in 2018, with the expectation of using the “wisdom of the crowd” to gather data on patients’ experiences with mannitol. Vesely is an active chairman of the board; however, he works full time as a partner at the security company Sdema Group.

They didn’t establish a business model early on because, as Sadeh said, “we started this venture to make the world a better place.” As the company grew, however, one option did emerge. 

CliniCrowd is working with some food supplement companies to secure funding by doing research into their products, according to Sadeh. The over-the-counter products one might pick up at a pharmacy for allergies, a cold or the flu can’t claim anything about efficacy. But they can show data that might support such claims. Sadeh said that’s where CliniCrowd comes in, offering a platform for companies to gather information about patient experiences.

Still, the project remains mostly self-funded.

Using the ‘wisdom of the crowd’

The problem with mannitol, as the documentary explores, is that it’s an over-the-counter supplement labeled as safe by health authorities around the world. Pharmaceutical companies have little incentive to invest in a clinical trial, Sadeh said. A 2018 study in JAMA Internal Medicine puts the average cost of a trial at $19 million.  

In an interview in the documentary, Segal says having more doctors prescribe the supplement is a Catch-22 situation. They won’t give mannitol to patients because there’s no clinical trial, but no one would fund such a study.  

Nisan Katz speaks at an event. (Photo by Nir Kafri)

“We’re not against the pharma company; we’re not against doctors. Because this system is usually about economic and profit, it’s understandable to me,” Katz said. “Sometimes, in some situations, it can be bad for patients.”

Katz said he interviewed a CEO of a big pharmaceutical company but decided to cut it. The CEO said what Katz already knew: There wasn’t an economic incentive. Instead, he opted to use an anonymous interview with a pharmaceutical company employee. 

Since CliniCrowd launched, 2,000 Parkinson’s patients from 54 different countries have participated, 1,076 of whom they now have follow-up data, according to an email from Sadeh

In the future, they are hoping to be able to make use of wearable devices that can “objectively track medical conditions” and avoid potential selection bias —  that is, people with positive results being the only ones to report their outcomes. He added that the data analytics platform they use also accounts for potential statistical pitfalls.

“You will make your own decision to take it or not take it, but at the end of the day, we really want to get the FDA approval and European drug authority,” Sadeh said. “Today everyone can buy it. It’s a safe solution.”

The revolution has just begun 

Hadassah Medical Center is conducting a Phase 2 trial testing mannitol for Parkinson’s under the supervision of neurologist David Arkadir. No corporation is funding this study; rather, the Ministry of Health of Israel has been providing grants for substances that can’t be patented. Mannitol was one of them. 

In addition to mannitol, CliniCrowd is looking into how cinnamon extract potentially could prevent Alzheimer’s or help existing patients with user-reported outcomes.

Katz, 46, had wanted to make movies since he was a child. In his 20-year career as a documentarian, he’s covered an Israeli community formed in India, the conflict between Israel and Palestine, and stories of immigrants playing soccer around the world. 

But for this documentary, Katz said, “I can really believe I can make a change and impact millions of people.”

Vesely had a chance to see the documentary at a private screening earlier this month. It’s currently available on Vimeo’s on-demand service. He hates to see himself on screen, but it was well worth it for him. 

“I know it served the mission, that it will inspire other patients and spread the notion about mannitol, about recruiting the wisdom of the crowd to the conservative healthcare,” Vesely said.

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CHMP Favors EU Approval of Inbrija to Treat Parkinson’s Off Periods

CHMP recommendation

The Committee for Medicinal Products for Human Use (CHMP) — an arm of the European Medicines Agency (EMA) — is recommending that Inbrija, by Acorda Therapeutics, be approved to treat off periods in Parkinson’s patients on a carbidopa/levodopa regimen.

The European Commission will review CHMP’s positive opinion, with a decision expected before year’s end.

“We are delighted that Inbrija has achieved this important milestone, and look forward to the EC’s final decision later this year. There are approximately 1.2 million people in the EU living with Parkinson’s. We estimate that 40% of these individuals experience off periods, which are considered extremely disruptive,” Ron Cohen, MD, president and CEO of Acorda, said in a press release.

Inbrija is a self-administered, inhaled formulation of levodopa developed to treat off episodes. These periods, when levopoda wears off before a new dose can be taken, are characterized by the re-emergence of Parkinson’s motor symptoms, and are typically more common as the disease progresses.

Inbrija delivers a precise dose of levodopa to patients’ brains that, because it is inhaled, bypasses the need to be absorbed in the digestive system. As such, it can deliver a higher and more consistent levodopa dose to the brain.

Inbrija is approved by the U.S. Food and Drug Administration (FDA) to treat Parkinson’s symptoms during off episodes. 

CHMP’s decision was based on clinical data from the Phase 3 SPAN-PD clinical trial (NCT02240030). The study evaluated the safety and effectiveness of two doses of Inbrija — 84 mg and 60 mg — or a placebo taken up to five times a day in 351 Parkinson’s patients experiencing off periods. Treatment was maintained for 12 weeks.

Results showed that Inbrija significantly improved patients’ motor function compared to placebo. Researchers found no safety concerns. The most common adverse events were cough, upper respiratory tract infection, and throat irritation.

Trial outcomes were published in The Lancet Neurology, in the study “Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson’s disease: a randomised, double-blind, placebo-controlled phase 3 trial.”

Inbrija was also studied in two long-term Phase 3 trials — the CVT-301-005 trial (NCT02352363) and the CVT-301-004E study (NCT02242487) – that evaluated Inbrija used up to five times daily for 12 months.

Researchers found no changes in treated patients’ lung function compared with standard levodopa treatment, supporting Inbrija’s safety as an off-period medication.

Efficacy data from the CVT-301-005 trial also confirmed that Inbrija eases problems with motor function that emerge in off periods. Treatment was found to enable symptom control within 60 minutes of the dose and lowered the length of patients’ off times.

Acorda’s European application covers all European Union countries, as well as Norway, Liechtenstein, and Iceland.

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Acorda Asks European Union to Approve Inbrija for Parkinson’s Off Periods

Inbrija approval request

Acorda Therapeutics has asked the European Medicines Agency to approve Inbrija (CVT-301) to reduce the periods when the standard Parkinson’s treatment carbidopa/levodopa is not working.

Inbrija is a self-administered, inhaled levodopa therapy. Acorda developed it to reduce the time when standard levodopa treatment wears off — periods known as off times.

Both movement and non-movement symptoms return during off times. About half of  patients taking standard levodopa have off periods, which become more frequent and severe during the course of the disease.

Inbrija was designed to deliver a precise dose of a dry powder form of levodopa to patients’ brains. The powder form bypasses the digestive system, preventing delays in the medication kicking in.

Acorda filed a marketing authorization application asking the European Union to approve the therapy. The application included results from its 12-week Phase 3 SPAN-PD clinical trial (NCT02240030). The study assessed the safety and effectiveness of 84-mg and 60-mg doses of Inbrija’s administered up to five times a day in 351 Parkinson’s patients experiencing off periods.

Inbrija improved patients’ movement in comparison with a placebo, results showed.

In line with a previous Phase 2b trial, researchers found no lung safety concerns. The most common adverse events were cough, upper respiratory tract infection, and throat irritation.

Acorda presented the SPAN-PD results at the International Congress of Parkinson’s Disease and Movement Disorders in Vancouver, Canada, in June 2017.

The application included the results of two long-term Phase 3 safety trials as well. The CVT-301-005 trial (NCT02352363) covered 408 patients, and the CVT-301-004E study (NCT02242487) 325 participants.

Researchers found no changes in the treated patients’ lung function, compared with standard levodopa treatment. Taken together, the findings indicated that Inbrija was safe as an off-period treatment, Acorda said.

The U.S. Food and Drug Administration accepted Acorda’s New Drug Application for Inbrija in February 2018. It expects to decide by October 5 whether to approve it.

U.S. regulators refused to accept Acord’s initial application due to concerns over the manufacturing of Inbrija. The company addressed the questions in a revised application.

Acorda’s European application covers all European Union countries, as well as Norway, Liechtenstein, and Iceland.

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Source: Parkinson's News Today