Top 10 FA news stories of 2024
Of most interest to readers were updates on Friedreich's ataxia treatments
Throughout 2024, Friedreich’s Ataxia News brought readers detailed coverage of the latest clinical research related to Friedreich’s ataxia (FA), as well as updates on scientific breakthroughs and developments in treatment.
Here are the top 10 most-read stories of last year, each with a brief description. We’re excited to continue serving the FA community in 2025.
No. 10 — PTC announced plans to seek FDA approval of vatiquinone for FA
In October, PTC Therapeutics announced its plan to file, by the end of the year, for U.S. Food and Drug Administration (FDA) approval of oral vatiquinone as a treatment for FA. That request was to be largely based on the overall positive results of the company’s Phase 2/3 MOVE-FA clinical trial. Although the therapy failed to outperform a placebo in slowing disease progression at 18 months, as measured by the modified Friedreich Ataxia Rating Scale (mFARS), it slowed the decline in subscales of upright stability and bulbar symptoms — those affecting the face and neck. Moreover, almost three years of data from the trial’s extension study showed that vatiquinone slowed total mFARS scores by about 50% compared with untreated patients.
No. 9 — Vatiquinone shown to extend walking ability among FA patients in trial
Data from the MOVE-FA trial showed that treatment with vatiquinone delayed the loss of walking ability by about nine months among children and young adults with FA. While the trial didn’t achieve its overall goal of slowing mFARS progression, it did demonstrate a significant benefit relative to the placebo regarding fatigue reduction and function in the upright stability subscale of the mFARS. According to researchers, evaluating upright stability is a more sensitive measure to capture meaningful changes that predict the loss or preservation of walking ability.
No. 8 — Voyager selects gene therapy candidate for FA for future clinical trials
Using its TRACER capsid discovery platform, Voyager Therapeutics early last year selected a new adeno-associated virus (AAV) shell, or capsid, that it would test in clinical trials in FA. The capsid can access the brain and deliver a healthy copy of the FXN gene, which is defective in people with Friedreich’s ataxia. The company aims to target brain areas that are difficult to reach with other therapies following an infusion into the bloodstream. In partnership with Neurocrine Biosciences, the companies expect to begin clinical testing this year.
No. 7 — Mitochondria function in FA cells restored by immune protein activator
In a cell-based model of FA, exposure to a small molecule called honokiol restored the function of mitochondria, the energy-producing structures within cells that are impaired in FA. Like resveratrol, the naturally occurring honokiol, a SirT3 activator thought to have antioxidant activity, also reduced the number of harmful reactive oxygen species in mitochondria and increased energy production in lab-grown FA nerve cells. The researchers, from Spain, suggested that the molecule could be a strategic therapy for the inherited, progressive disease.
No. 6 — Long-term extension study doses first FA patient with nomlabofusp
In March, a long-term, open-label extension (OLE) of a Phase 2 clinical trial testing nomlabofusp — an investigational therapy for FA formerly known as CTI-1601 — dosed its first patient. Data from the Phase 2 study had shown that daily injections of nomlabofusb, administered subcutaneously, or under the skin, led to dose-dependent increases in levels of frataxin, the protein deficient in FA patients. Larimar Therapeutics, the therapy’s developer, said it will use data from the OLE and completed clinical trials to support an application seeking the therapy’s accelerated approval in the U.S.
No. 5 — Frataxin levels boosted by vitamin D supplement in small trial
In a small clinical trial, a low dose of calcitriol, an activated form of vitamin D, significantly increased frataxin protein levels among people with FA. While the trial participants didn’t report any notable changes in neurological and motor symptoms, frataxin levels — measured in platelets cell fragments that help blood clot — demonstrated a small but statistically significant increase after a year on calcitriol. Based on these findings, the researchers called for future studies with more patients, higher doses of calcitriol, and longer follow-up times.
No. 4 — New FA treatment candidate DT-216P2 may start clinical testing in 2025
In August, Design Therapeutics announced that it would begin clinical testing of DT-216P2, a novel experimental treatment for FA, in 2025. Developed using molecules called GeneTACs, the company’s new candidate therapy is designed to activate the faulty FXN gene in FA patients. It aims to restore frataxin production, thus slowing disease progression and easing FA symptoms. A first-generation molecule called DT-216 had been shown to work as intended in a Phase 1 study. Still, participants developed reactions to some ingredients in the formulation, prompting Design to rework the therapy to avoid these side effects.
No. 3 — FDA grants orphan drug status to FA cell therapy PPL-001
The FDA in September awarded orphan drug designation to PPL-001, Papillon Therapeutics‘ cell therapy for FA. The regulatory agency grants this status to treatments with the potential to improve medical care for rare diseases, or those affecting fewer than 200,000 people in the U.S. The designation encourages pharmaceutical companies to develop such treatments by giving them regulatory and financial advantages. The use of PPL-001 involves removing hematopoietic stem and progenitor cells, which give rise to several types of blood and immune cells, from an FA patient. The FXN genetic defect is corrected via gene editing, and the cells are reinfused into the same patient.
No. 2 — Normal FA cell function restored with gene-editing therapy
In April, researchers published a study demonstrating how a gene-editing therapy — the one developed into PPL-001 by Papillon — reversed several FA-related features in patient-derived nerve cells. These features included nerve cell structural changes, increased cell death markers, mitochondria dysfunction, and oxidative stress, which is a type of cellular damage associated with FA. The gene therapy also restored the normal function of a cellular compartment called the endoplasmic reticulum, which might play a role in driving nerve cell death in FA.
No. 1 — Gene therapy reverses severe FA-related heart defects in mice
In a mouse model of severe FA, a new gene therapy reversed heart problems, lowered blood markers for heart muscle damage, and extended survival. The FA mouse model, designed to lack frataxin in heart and skeletal muscles, showed progressive weight loss and heart problems, leading to death at about 2.5 months of age. Mice received treatment with a full-length FXN gene, delivered to cells using a harmless viral vector at six weeks, when heart problems already existed. All FA mice treated with the gene therapy were alive at 2.5 months, and echocardiography, or ultrasound, for heart function, and blood tests for a biomarker of heart muscle damage, showed no notable differences between treated FA mice and healthy mice.
At Friedreich’s Ataxia News, we hope our stories and reporting throughout 2024 positively impacted the lives of those with FA. We are seeking to provide ongoing support and information to the FA community in 2025.
A very happy new year to all our readers!
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