New treatments are coming for patients living with FD. Find out why we need a natural history study and learn how you can do your part.

MAKING PROGRESS

New drugs to halt the progressive aspects of FD are set to enter the clinic in 2019 for testing. Progress in FD is happening at faster pace than ever before and “clinical trials readiness” has become a buzz word in the complex world of drug development for rare diseases.

Unlike conventional clinical trials that can test new drugs in large population, developing drugs for FD requires ingenuity, scale and a different approach. The numbers are way smaller, with only a few hundred children and adults worldwide suffering from the disease.  This is where natural history studies come in to play. Classic study designs require half the patients to take a placebo (sugar pill) so that they can be compared to those receiving the active drug. This can be avoided with thorough and abundant natural history data. In this way, the effect of an active drug can be compared to what happened  in the natural history study before the patients received the new drug.

THE VISION

In many ways, FD has become the blueprint for translational research and has paved the way to show how collaboration can blossom into real opportunity. Despite the complexities of the disease, we have a good understanding of how patients with FD evolve overtime and what features of the disease get worse.

In 2008, husband and wife team Dr. Horacio and Lucy Kaufmann joined the Center, and  started to recognize some peculiar traits that seemed to be worsening overtime. The children with FD could see, whereas the adults were struggling to read. The children with FD were somewhat clumsy, but the adults were falling and unable to walk down the hallway without holding on to the wall. Vision and gait ataxia are now recognized as progressive neurological aspects of the disease.

In 2016, the Kaufmanns launched a new initiative for patients with FD to start a formal natural history study. They built on the original idea of Dr. Axelrod and Dr. Maayan who had been collecting and sharing information for decades. Dr. Lucy Kaufmann explained “We took that initial idea of following patients in a collaboration and decided to plan exactly what routine information we should be collecting each year. We can use this benchmark information to help drug development and drug approvals”.

COLLABORATION

In 2017, the team got the natural history study approved at NYU. In 2019, the study was also approved in Israel and the first international recruiting site opened at Tel Hashomer Hospital. This formal arrangement means that we have an international collaboration that can help patients participate regardless of where they live. More sites are expected to join the study soon.

Successful natural history studies require collaboration, and FD is no exception. When patients are seen, the medical team collects a series of vital pieces of information that track how a patient is at a particular time. That information is like gold. Combining the data from multiple different patients allows one to pick out trends and see what are the unmet needs of the patients. Having a formal natural history study means that the data collection can be standardized so there is less noise. We can train investigators at different sites to collect information in the same way.

TARGET ENGAGEMENT

Understanding the progressive aspects of the disease have given us a target. We want to keep FD patients seeing and moving independently, explained Dr. Kaufmann. New drugs are needed to fix  what is happening inside the nerves and causing the cells of the eye and motor coordinating system to malfunction. We are lucky to have the brightest minds working on the biological strategies to save the nerves, but we still need to do our part.

To test new therapies currently being developed at the bench, we need something to compare to.

Since 2010, the Center has been collecting high-definition scans of the back of the eye, which show a progressive thinning that begins at an early age. Putting this information together has given us an understanding of what is the natural evolution of the degeneration of the eye. In other words, it is clear what happens to vision if we don’t prevent the nerve loss. With the availability of the eye natural history data, we have a fairly good understanding of why one-third of people with FD go blind. We have to change this. If we develop a drug to save the nerves, we can measure how it changes the natural progression of the disease using the eye as a window.

The same it true for the gait. The team has been rating and recording the way patients with FD move using the same scale for the last 5-years. We can see how they worsen, we can see what are the benchmarks that need to change.

NATURAL HISTORY GAME-CHANGER

Having this high-quality natural history data available becomes a game changer for developing new drugs and planning innovative clinical trials. Now it is time for all patients to participate. We want the clinical information from as many patients with FD as we can. This will help us with the challenges that are faced by research teams that are invested in finding cures for rare diseases in small populations. If we can do this well, it could mean that patients won’t have to take a placebo pill during a clinical trial. We can show that a new treatment is slowing or has restored nerve function, if we can compare it to the natural history of the disease.

YOUR PART

Participating in the natural history study is easy. You have to sign permission (consent or ascent) to have your data included in the database alongside with “standard of care” treatments, the drugs/therapies that are given to treat the symptoms/complications of the disease.

The type of clinical information collected is routine. It includes vital signs, medications, nutrition/growth parameters, neurological scores, vision tests, blood pressures, blood test results, and pulmonary function tests. These are the tests that all patients with FD are recommended to have routinely for their standard medical care. If they agree, patients and relatives can also give a sample of blood that can be used to measure the levels of the defective protein and mRNA.

Patients can also send information from their own doctors.

The natural history study is currently approved at the following recruiting sites:

NYU School of Medicine, NY, NY (here)

Tel Hashomer Hospital, Tel Aviv, Israel.

Stay tuned for additional recruiting sites soon to be added.

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If you want to know more about how to participate in the natural history study, call us at the Center (212-263-7225).