Prof. Anna Potulska-Chromik on treatment and hopes for patients with Friedreich's ataxia

What is Friedreich's ataxia? Are we able to determine which group of patients it affects, in terms of numbers but also in terms of structure?

Friedreich's Ataxia is a genetically determined, neurodegenerative, progressive disease. It primarily affects the musculoskeletal system. A patient with Friedreich's ataxia develops the so-called ataxia symptom, which we can translate as motor awkwardness. As a result, the patient has difficulty walking, exercising or participating in physical education classes. These symptoms unfortunately progress. There is trembling in the upper extremities, a high amplitude of movement, making it a problem even for the patient to make himself a sandwich, prepare any food or pour water into a glass. As in most genetic diseases, we also have other systems involved and somewhat less typical symptoms with which the disease can begin in some patients. This would be scoliosis, cardiomyopathy or optic nerve atrophy, hearing damage. With time, speech disorders also appear. This is a derivative of ataxia. Just as we need fluidity of movement when walking or preparing food for ourselves using our hands, we also need some fluidity in language, laryngeal muscles and vocalization. Our patients, unfortunately, are also beginning to speak less and less clearly. What's more, they may develop swallowing disorders that pose a danger when eating. This can lead to unpleasant consequences, such as choking. And this is already a life-threatening condition. This disease unfortunately progresses and ends in premature death. Patients generally pass away in the fourth or fifth decade of life.

What is the diagnosis and what can be offered in treatment?

Since this is a genetic disease, we need to do a genetic test. Nowadays we are all very enthusiastic about new methods, next-generation sequencing, or so-called NGS, hoping to trace all the genes. In Friedreich's ataxia, we have the difficulty that here the mutation is a so-called dynamic one, which is that we have too much of the correct genetic material. These modern methods, primarily geared towards error detection, are not good methods that will detect to us that there is too much of something. The thing about genes is that sometimes where there are too many nucleotides, there is also a critical error that leads to disease. Another genetic disease involving the central nervous system, fairly well known and also with this kind of dynamic mutation specificity, is Huntington's disease. In these diseases, the money spent by the parents and patients themselves on state-of-the-art testing will be lost if Friedreich's ataxia is not thought of first. We can detect dynamic mutations with the fairly well-known and relatively inexpensive PCR method. But it must be performed in an experienced center. The specialist must ask a specific question: can the patient be diagnosed with Friedreich's ataxia? We ask a specific question, and not, as in the case of whole exome sequencing, we give some features that we see in the patient, we do not type any gene. The test takes a short time, and the patient should receive the result in a fairly short time.

What is the issue of treatment and access to treatment? Here, something seems to have changed in recent years?

Yes. In the world and in Europe, treatment has changed. A new molecule has emerged - omaweloxolone. In a nutshell, it affects the mitochondrial mechanism that is disrupted in Fridreich's disease through a genetic error, leading to a lack of frataxin. This new molecule does not act on the gene itself, it is not a gene therapy, but it reverses the effects of the damage to frataxin, and supports the function of mitochondria, our cellular power plants. As a result, the progression of the disease definitely slows down and can be stopped. This is a molecule that is being researched all the time, although registration studies have already been completed. In the United States, the molecule was registered in 2023, and also by the EMA in February this year. We expect that in accordance with the reimbursement law, the drug will also be available to our patients in Poland within the next year. We estimate that there may be about 150 patients in Poland, maybe more, because it's always jet that when a treatment comes out, then there is increased awareness among doctors about the disease. Then we have a better chance to diagnose patients quickly and start treating them sooner.