The first International Ataxia Research Conference, in 2015, was a milestone in the quest to find cures for the world’s 40 ataxias, diseases whose hallmark is the loss of muscular coordination.
Held in Windsor, England, it was the largest global convention yet to bring together patients, doctors, patient advocacy groups, researchers, pharmaceutical companies, regulators and others interested in the diseases.
Now a second IARC, set for Sept. 27-30 in Pisa, Italy, is generating excitement as well. One reason is that its organizers are trying to make it bigger and better than the first. Another is that it comes amid a backdrop of a lot of promising developments in ataxia research.
Scientists have identified more genes linked to ataxias, created additional tools for studying the diseases, are pursuing new gene therapy and gene editing approaches, are sending more therapies into clinical trials, and are stepping up efforts to adapt already approved drugs to ataxia, said three leaders of groups working on behalf of ataxia patients.
More companies are also working on treatments, according to the three: Jennifer Farmer, executive director of the Friedreich’s Ataxia Research Alliance (FARA); Jane Larkindale, FARA’s vice president of research and development; and Julie Vallortigara, Ataxia UK’s research projects manager. They recently spoke with Friedreich’s Ataxia News Today about the convention.
Largely because of increased industry interest in ataxia, 19 presentations at the conference will cover new treatments. Additional therapies will be covered in poster sessions.
FARA, Ataxia UK, and GoFAR are the main organizers of the upcoming conference, which is expected to attract about 350 participants, Farmer said. It’s fitting that the event is in Italy, because Italian researchers are active not only in ataxia research but in neurological disease research in general, Larkindale and Vallortigara added.
One of the conference highlights will be a roundtable at which five patients and caregivers discuss what they would like clinical trials to evaluate. The hope is that therapy developers use their perspectives in designing trials, Farmer said.
“Patients are the experts in their diseases,” Larkindale said. “We want patients to be engaged in what’s going on in the research world.”
“If you’re a scientist, a drug developer, the FDA (U.S. Food and Drug Administration) or the EMA (European Medicines Agency), you want a drug that treats symptoms that are important,” Farmer said. You also want to know what side effects patients are willing to endure to obtain symptom relief.
And “you also want to have a good understanding of what the burden of the disease is,” Farmer added. “There’s no way that researchers or people in the companies will be able to learn this if we don’t provide these kinds of opportunities for everyone to talk.”
Perspectives that patients offer can be eye-opening, she said. When patients share an often disheartening story of the hoops they went through to obtain their ataxia diagnosis, listeners “understand that ‘Oh my gosh, you had to go to four or five different specialists before you got to the right one?,’” Farmer said.
The “real learning” that occurs when patients share their stories may help “improve that diagnostic journey,” she said.
The convention will focus more on inherited ataxias rather than those stemming from head trauma or environmental causes because genetic ataxias are the most numerous, Larkindale said. And as Friedreich’s ataxia is the most common inherited form, many of the presentations will deal with it.
Scientists continue to identify genes whose mutations are linked to ataxias, Vallortigara said. Ataxia screening in the United Kingdom now covers more than 100 genes.
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One of the hottest topics at the convention will be using gene therapy to combat ataxias, an approach that essentially involves replacing faulty genes that cause a disease with healthy ones that restore normal function.
“Gene therapy has just made leaps and bounds in the last couple of years,” Larkindale said. “There’s going to be a lot of discussion about that because it’s a big, exciting new area.”
Within this field, a topic expected to be given considerable attention is a rapidly evolving type of gene editing known as CRISPR, which allows permanent modification of a gene. Gene editing basically involves making changes in DNA, the building blocks of genes.
CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, allows scientists working on therapies to quickly create models to test hypotheses, Larkindale said. Scientists have also begun thinking of it as a way to treat some diseases, she added.
New approaches like gene editing, plus new cell and mouse models of ataxias, have helped scientists learn more about the gene mutation that generates the faulty frataxin protein involved in Friedreich’s ataxia, Larkindale said. Some of this work “couldn’t be done a few years ago,” she said.
“We’re beginning to get more understanding of how the epigenetic silencing of the frataxin gene is occurring,” she said. That will open exciting new therapy possibilities, as “we can now get to therapies that really get at the basis of the disease,” Larkindale said.
Gene therapy, gene editing, new cell and mouse ataxia models, and orphan drugs acts in the United States and Europe have prompted a number of pharmaceutical companies to jump into ataxia therapy development in the past few years, Farmer said. The drug acts give companies financial and other incentives to work on treatments for rare diseases.
The growing industry interest will be reflected at this year’s conference, with about 24 companies expected to attend, versus 14 to 16 at the initial IARC convention two years ago, Larkindale said.
One reason some are getting involved is that they have drugs approved for other diseases that they may be able to adapt to ataxia, Farmer said.
These crossover possibilities include approved treatments for such neurological diseases as muscular dystrophy, Huntington’s disease and Parkinson’s disease, Larkindale added.
“A lot of these ataxias involve various organs involved in other diseases,” she said.
In addition to homing in on specific research, conference presentations will include overviews that Larkindale believes offer important perspectives on disease understanding and therapy development.
For example, Dr. Francesco Sacca will discuss what’s been happening in clinical trials of ataxia therapies and what new trials will be covering. “I think that’s going to be a really interesting summary of where we are,” Larkindale said.
Presentations set for the conference include:
The rapid progress in next-generation genetics of ataxias: insights, challenges, and next steps.
Overview of the natural history of Friedreich’s ataxia.
Long-term quality of life, depression and activities of daily living in the most common spinocerebellar ataxias (SCA1, SCA2, SCA3, SCA6).
CCFS: a quantitative score of cerebellar dysfunction and evolution in Freidreich’s ataxia.
Exercise stress testing on adaptive equipment is feasible and reliable in Friedreich’s ataxia.
Auditory dysfunction and its remediation in individuals with spinocerebellar ataxia.
Summary and lessons learned from Friedreich’s ataxia clinical trials.
Innovative trial designs for rare diseases, with focus on use of innovative endpoints and potential use of registry data.
Safety, efficacy and pharmacodynamics of omaveloxolone in Friedreich’s ataxia patients (MOXie Trial): Part 1 results.
Overview of viral gene therapy approaches for genetic diseases.
Gene therapy for Friedreich’s ataxia.
TALEN and CRISPR gene editing for treatment of Machado-Joseph disease.
Roundtables and other events will consist of:
Roundtable discussion on patient perspective on clinical trials and studies.
Roundtable discussion on clinical trial designs for ataxias.
Mentoring session for young investigators.
More than 200 poster sessions.
Speaking of the key role that GoFAR plays in organizing the conference, Larkindale noted that Italians are making important contributions to ataxia research.
In fact, she said, “Italy has a history of good research in a lot of rare diseases.” Added Farmer, “there are a lot of Italians in neurosciences in general.”
Although the convention will be a place where the ataxia community can soak up information, Farmer, Larkindale and Vallortigara said such meetings are also crucial to getting researchers fired up and in facilitating collaboration. “There’s no better way to do that than real-time, face-to-face,” Farmer said. “New information is communicated more efficiently and more quickly than waiting for someone’s research publication to come out.”
As for the enthusiasm a convention builds, Larkindale said she hopes that researchers “feel excited and want to work extra hard and collaborate” with others they’ve “just met who have great ideas.”
Farmer agreed. There’s no better way of “pulling the scientific community together” on the ataxia challenged than a conference like IARC, she said.
Friedreich’s Ataxia News will be covering the IARC meeting, offering its readers daily summaries of the latest advances and discoveries in ataxia research.