Michael J. Fox Foundation finds promise in Israeli Parkinson’s treatment

The patented L-Dopa Patch will alleviate the symptoms of patients who suffer from motor complications by overcoming the short half life of levodopa through continuous transdermal delivery.The Michael J. Fox Foundation for Parkinson’s Research believes that Israeli company NeuroDerm has …

The patented L-Dopa Patch will alleviate the symptoms of patients who suffer from motor complications by overcoming the short half life of levodopa through continuous transdermal delivery.The Michael J. Fox Foundation for Parkinson’s Research believes that Israeli company NeuroDerm has the potential to offer hope to patients suffering from Parkinson’s disease. So much potential, in fact, that the foundation is awarding them a $490,000 grant to aid in research on their transdermal skin patch, used to maintain steady levels of Levodopa (L-Dopa) in patients with Parkinson’s disease.

L-Dopa is the most efficient drug for the treatment of Parkinson’s disease through the skin, and NeuroDerm’s sophisticated patch maintains constant blood levels of the drug.

“What we are hoping to offer is really a very simple solution to a very large problem for a majority of patients that have very limited options today, says NeuroDerm’s Chairman of the Board Dr. Oded Lieberman.

“70-80 % of patients take levodopa orally, and they eventually suffer because continuous administration of the drug has been a challenge since it started being used 30 years ago. We are offering a very simple potential solution to this.”

Since its foundation in 2000, the Michael J. Fox Foundation has funded approximately $74 million dollars in research in order to help develop a cure for Parkinson’s disease, a disease that has affected more than a million people in the US and four million in all industrial countries.

Michael J. Fox, a popular television and film actor, was diagnosed with young-onset Parkinson’s disease in 1991. Seven years later, he disclosed his condition to the public and announced that he was committing himself to the campaign for increased Parkinson’s research.

Fox announced his retirement from the hit situation comedy Spin City in January 2000, and launched The Michael J. Fox Foundation for Parkinson’s Research, which has been the focus of his energies ever since, with the goal of raising much-needed research funding for and awareness about Parkinson’s disease.

The award granted to NeuroDerm was made under the foundations Clinical Discovery Program, an investigator-initiated, peer-reviewed program that provides funding for clinical research projects over the course of up to three years.

The highly selective award is chosen by a committee of biostatisticians, clinicians, and clinical trial experts, among others, and is given to a company believed to have a significant chance of greatly improving the lives of patients with Parkinson’s disease.

The honor of being recognized by such a prestigious group of people will invariably help to advance NeuroDerm, and will affect the company both directly and indirectly, Lieberman reports.

“The first and foremost direct advantage is the money, which is nice. It is always nice to receive a gift of half a million dollars. There is also the support of the foundation, which is of no less importance. One should bear in mind that the review was done by bio statisticians, clinicians, professional experts, etc., and having them look over our program, and having them approve it, is a benefit and a resource. That is a second direct advantage,” he told ISRAEL21c.

But beyond just the obvious advantages, the award has also helped NeuroDerm indirectly, bringing them international recognition.

“There has been an immense response following this grant from all sorts of various organizations and companies,” says Lieberman. “A number have approached us, and that is a real benefit. We are a small company and that is a primary activity for us, to chart our strategy for the future, to take into account partnerships with pharmaceutical companies, and now they have been contacting us.”

The start-up company operates under the roof of the Ofakim technological incubator with funding from the Chief Scientist of the Ministry of Industry and Commerce and a private investor. Founded ten years ago, the company’s goal is to solve the problem of continuous delivery of L-Dopa in Parkinson’s disease.

As a small Israeli company, the monetary aid and recognition abroad will undoubtedly help NeuroDerm to advance more quickly, allowing them to offer potential help to Parkinson’s patients as soon as possible.

“This Clinical Discovery Program grant is part of our focus on speeding highly relevant treatments to people living with Parkinson’s disease,” said Deborah W. Brooks, president and CEO of The Michael J. Fox Foundation. “We believe that improved delivery through continuous levodopa administration, such as NeuroDerm’s prospective patch aims to achieve, could potentially result in a significant improvement in patients’ day-to-day lives.”

It is this aspect that Lieberman agrees is the most important. “This award basically guarantees support – monetary and otherwise – for the next clinical development steps that we have. We are looking at a simplified clinical development, so this is significant. One of course must think first and foremost about the patients.”

NeuroDerm foundets – Ben Gurion University of the Negev Professor Eli Heldman, Dr. Moshe Kushnir, a neurologist at Kaplan Hospital in Rehovot and Dr. Haim Schlesinger, an analytical chemist – emphasize the potential hope that receiving this award will allow them to bring to Parkinson’s patients.

“We are delighted that the Foundation has recognized the immense impact our program may have on the lives of many Parkinson’s patients,” said Heldman and Kushnir in a statement. “We hope that NeuroDerm will be able to offer a practical solution to patients suffering from damage caused in late-stage Parkinson’s disease and to earlier stage patients wishing to slow down the development of late motor complications.”

It is speculated that dyskinesias, the disruptive, jerky movements associated with long-term L-Dopa therapy, results from the sharp fluctuations in dopamine blood levels that occur when levodopa is given orally. The patented L-Dopa Patch will alleviate the symptoms of patients who suffer from motor complications by overcoming the short half life of levodopa through continuous transdermal delivery.

And, although IV infusions are also effective, the patch, unlike IV infusion, is a non-invasive device suitable for prolonged use. Laboratory results indicate that continuous administration of L-Dopa can prevent the acceleration of the development of later stage complications such as freezing or uncontrolled movement.

“When the drug is taken orally, the blood level rises and falls and with time this discontinuous effect creates damage to the system,” Kushnir told ISRAEL21c. “Intermittent stimulation of dopamine receptors during prolonged treatment with L-Dopa is a major factor in the development of motor complications in Parkinson patients. And, after a few years, patients don’t respond to the drug.”

According to Heldman, developing the drug was a major challenge because of three problems: it is not soluble, it is unstable, and does not penetrate well through the skin. The unique formulation developed by NeuroDerm solves all these problems. The product is composed of a formulation and a device for continuous trans-dermal delivery.

An important feature of the novel L-Dopa Patch is its move-ability. Attached to the skin without adhesive, the patient can change the location of the patch to suit his or her comfort needs. The portable device that serves as a reservoir for the drug easily attaches to a belt.

“Other products on the market – long-acting drugs, agonists – cause serious side effects and are less effective than L-Dopa; controlled release preparations have low bio-availability and their effect is intermittent,” says Kushnir. Two companies are working on trans-dermal delivery of synthetic agonists, but it is doubtful that they would be an improvement over the oral drugs already available.

Lieberman, too, notes the abundance of other drugs currently being developed. “There are so many solutions being developed and offered by different organizations and companies, and therefore this is a very, very powerful validation of what we are doing, which is both original and simple. I think that companies from the US and elsewhere have a genuine difficulty in separating the wheat from the chaff, so to speak, and by having the Michael J. Fox Foundation go through and select the various programs, this helps them focus on the most promising development programs that are around.”

But beyond just its significance for Parkinson’s disease and NeuroDerm in particular, Lieberman believes that winning this award can have a positive effect on other science-based companies in Israel.

“I think that this is a very good example of how original scientific work from Israel has the potential to make a real impact in the world. Having done what we have done is on the one hand very promising and impressive, but on the other hand an example of what can come out of work from Israel. At the same time, we fully realize that we are a small company with very limited resources and that getting this full benefit of what we are doing will at some stage require a collaboration from a large partner. This is a good model that I know other companies are following. Israeli companies must concentrate on what they are good at and not be hesitant to collaborate.”

Situated on the fringe of the developed world as far as drugs are concerned, Israeli companies face extra challenges that US and European companies don’t have to deal with.

“We are far away and the local resources are limited, so we have to be very careful on what we decide to do by ourselves and what we decide to collaborate on,” says Lieberman. “Being a small company in a small country means we need to rely on international collaborations all the way. Even in simple and mundane steps that are overcome easily in the US, we have to collaborate with far away places. We have to be better and more careful than someone in the middle of the Silicon Valley or even Boston.”

And as a result, NeuroDerm is even more appreciative of this award, well-aware that it will greatly advance them in their work to bring help to Parkinson’s patients.

As Lieberman points out, “It is an international award, but for us, being a non-American company, it is always an extra challenge to keep up with the best that the US has to offer, and this award gave us an immense sense of gratification.”

And it give Parkinson’s sufferers in the US and elsewhere reason for hope.