One of the most encouraging developments in ataxia research these days is a surge in therapies advancing to the clinical trial stage.
This has put a premium on trial design, which means that many of those going to the Second International Ataxia Research Conference (IARC) in Pisa, Italy, set for Sept. 27-30, look forward to attending design presentations.
Among them are patients, who have a vested interest in trial design: They want clinical studies that address their most critical treatment needs.
Others interested in trial design include Julie Greenfield, the head of research at Ataxia UK, and the nonprofit’s CEO, Sue Millman. The two leaders of Britain’s premier ataxia organization are also eager to attend conference sessions on new treatment approaches, including gene therapy and adapting approved treatments for other diseases to ataxias.
Greenfield and Millman are also excited about the event’s panel discussions, they said in an interview with Friedreich’s Ataxia News. One will feature patients, and another scientists and representatives of drug companies working on therapies for these neurodegenerative diseases.
Patients will discuss both how ataxia affects them in their daily lives and the importance of designing trials that address their most important needs, Greenfield said. The panel’s entire focus will be trial design, according to the conference program.
Millman said Ataxia UK hopes the information that comes out of both discussions furthers her organization’s goal of “seeing that trials are suitable to the needs of patients — that they’re set up in ways that enable the maximum participation of patients.”
Supported research and outcomes
Ataxia UK is one of the conference organizers, along with the Friedreich’s Ataxia Research Alliance, or FARA, in the United States, and the Italian ataxia organization GoFAR, which is hosting this year’s event. Ataxia UK was the host organization for IARC’s first global conference, in Windsor, England, in 2015.
Like other patient advocate groups, Ataxia UK’s objectives include improving patient treatment, funding research that leads to therapies, and promoting collaboration among members of the ataxia community.
A key piece of Ataxia UK-funded research that the Pisa conference will cover is the natural history of Friedreich’s ataxia (FA), the most common of more than 100 ataxias. A number of nonprofit organizations are helping fund the research, which the European ataxia federation EuroAtaxia is coordinating.
The term “natural history” refers to how a disease progresses over time. By understanding the stages in its development, scientists may be able to develop therapies that doctors can administer at crucial points to slow the disease’s progression from one step to another.
This is particularly important in ataxias, because changes in patients’ disabilities can be subtle, Greenfield said.
“You look at [patients’] coordination and balance, for example, and study them every six months or a year” for change, she said. “If you understand the natural progression of the disease, when you then introduce a treatment, you can determine if the progression is slowing down or stopping as a result of the treatment. This is extremely important in clinical trials.”
In addition to movement and balance problems, many people with ataxia have trouble talking and hearing.
Another Ataxia UK-funded project on the IARC agenda is a clinical trial testing FM hearing devices in patients with spinocerebellar ataxias.
“It looks promising for helping patients” who have difficulty hearing when there is background noise, Greenfield said. The trial has suggested that the device can cut through the noise.
Another Pisa presentation whose research Ataxia UK has funded is the work of Spanish scientist Javier Diaz-Nido into the possibility of developing FA therapies around neurotropic factors. These molecules, which are small proteins and peptides — or portions of proteins — promote neuron survival. Scientists believe neuron death is the cause of most neurodegenerative diseases like ataxias.
An important tool for studying a disease, and creating treatments for it, are cell and animal models that mimic its characteristics in humans. The models help scientists develop therapies that can then be tested in clinical trials involving humans.
About 15 years ago, Ataxia UK supported British researcher Mark Pook’s development of a mouse model of FA that scientists worldwide now use in research today. The organization has also funded the development of induced pluripotent stem cell models of ataxia.
Scientists continue to develop models of ataxia that can improve researchers’ work, and the Pisa conference will include presentations on several new models.
Priority on collaboration and patients
Millman said Ataxia UK made facilitating collaboration on treatment and research a priority a decade ago, and conferences like IARC are important to generating and strengthening such collaboration.
Collaboration is crucial partly because ataxia is so complicated. Each of the 100 or so varieties of the inherited disease stems from different gene mutations.
“Ataxia UK firmly believes that no one charity, pharmaceutical company or laboratory is going to crack these ataxia conditions” by themselves, Millman said.
The three organizers of the Pisa conference — Ataxia UK, FARA and GoFAR — have already collaborated on a number of research projects, she pointed out.
Because Ataxia UK deals with all ataxias, it also works with other European ataxia patient advocate groups. In fact, it will be taking part in a Euroataxia symposium in Pisa in conjunction with the IARC conference. Euroataxia is made up of ataxia patient groups in several European countries and Israel.
A survey of participants at the first IARC in England showed how important such gatherings are to facilitating collaboration, Millman said. Of those who responded, 86 percent said they made new contacts at the event that they believed would enhance their work.
The Windsor conference, which was then the largest gathering of the ataxia community — about 350 people — also helped “many scientists get to meet patients” for the first time, Millman said, adding that many researchers “were talking to us about the fact that they were scientists and they never get to meet a patient.” The interaction was probably particularly beneficial to young researchers, she added.
Reasons for hope
Every day started with individual patients addressing participants.
These presentations, and patients’ and their families’ interaction with others at the event, underscored to the scientists that “it’s actually about patients,” Millman said. “It’s about patients getting worse, about patients living shorter and less fulfilling lives than they might otherwise.”
The underlying message was that “this isn’t any old research — it’s actually about people’s lives,” she said.
But the inspiration that emerged did not flow in one direction only. The scientists inspired patients and their families as well, by giving them hope, Millman said.
Those with ataxia and their families — particularly parents with young children — “are desperate to see some hope,” she said.
And the number of scientists who were there “is something that’s not forgotten” on patients and families, Greenfield said.
The Pisa conference will likely have about the same number of participants as the one in Windsor. Its organizers expect it to continue fostering collaboration in the ataxia community, inspiring scientists about the work they are doing, and generating new reasons for hope among patients and their families.