Top 10 SMA news stories of 2024
Updates on symptoms, treatments, and diagnosis of most interest to readers
Throughout 2024, SMA News Today brought our readers daily coverage of the latest clinical research and scientific breakthroughs related to spinal muscular atrophy (SMA).
Here are the top 10 most-read stories we published last year, each with a brief description. We’re excited to continue serving the SMA community in 2025.
No. 10 — Spinraza benefits SMA children with poor Zolgensma response
For children with SMA who have a less than optimal response to the gene therapy Zolgensma (onasemnogene abeparvovec-xioi), further treatment with Spinraza (nusinersen) may improve motor function and reduce nerve damage. That’s according to the results of interim data from a Phase 4 study called RESPOND, which specifically enrolled young children — ranging in age from 2 months to 3 years — whose SMA symptoms were substantial despite the one-time Zolgensma treatment. Six months after starting Spinraza, nearly all of the children had experienced improved motor function. Similar benefits were seen regardless of whether patients started Spinraza before or after 9 months of age, the data showed.
No. 9 — New technique helps elderly man with SMA to swallow better
Vacuum swallowing, a maneuver intended to help move food through the throat, helped a 67-year-old man with SMA to swallow better, according to a case report that detailed the patient’s problems with eating by mouth. The man’s difficulty in swallowing, known as dysphagia, had resulted in the placement of a feeding tube. With this new technique, he was trained to inhale air with his mouth closed for five seconds — creating negative pressure in the chest cavity and forcing food downward during swallowing. After about a month of 10 daily sets of five repetitions of training, food passing through the throat increased, and his nutritional status and body weight improved, according to the researchers.
No. 8 — Developmental delays seen in longer-lived SMA children in study
Nearly half of children with early-onset SMA develop neurodevelopmental problems, according to an international survey of clinicians. Such issues, including speech delays, intellectual disabilities, or difficulties with social communication and interaction, are now being seen in young patients who are living longer due to better treatments. Despite ongoing treatment with SMA-targeted disease-modifying therapies (DMTs), the survey reported neurodevelopmental problems in 272 of 624 patients, or more than 40% of the children. All but two patients in the study had been diagnosed with SMA type 1.
No. 7 — Voyager is working with Novartis to advance SMA gene therapy
At the start of 2024, Voyager Therapeutics announced that it would collaborate with Novartis to discover and develop next-generation gene therapies for SMA and other neurologic conditions. As part of their agreement, Novartis will have a target-exclusive license to Voyager’s TRACER AAV-based capsids, which are designed to enhance gene therapy delivery to the brain and spinal cord. In preclinical studies, TRACER-generated capsids demonstrated widespread gene activity compared with conventional AAV capsids like AAV9, used in the gene therapy Zolgensma. Moreover, the new capsids had 100 times higher penetration than AAV9, with fewer effects on the liver. Novartis also is responsible for developing and commercializing a resulting SMA therapy.
No. 6 — Phase 1b/2a clinical trial of AJ201 in SBMA was fully enrolled
In January of last year, Avenue Therapeutics shared that its Phase 1b/2a clinical trial of AJ201, its therapy candidate for people with spinal and bulbar muscular atrophy (SBMA), had completed enrollment. SBMA is a rare type of SMA caused by mutations in the AR gene, which leads to protein clumping that disrupts the function of nerve and muscle cells. In the trial, AJ201, designed to clear out disease-causing protein clumps, was tested in 25 adults with SBMA, who were randomly assigned to receive the experimental therapy or a placebo for 12 weeks, or about three months. The study has since been completed, but top-line data have yet to be released. A previous Phase 1 study showed the therapy was generally well tolerated in healthy adults.
No. 5 — Combination therapy found to synergistically boost SMN production
When combined with a therapy like Spinraza, low-dose risdiplam — the active ingredient in Evrysdi, an approved disease-modifying treatment for SMA — boosted the production of SMN, the protein that’s deficient in SMA, beyond that of each treatment alone. The combination also minimized the risk of off-target effects that can cause side effects at higher doses. Despite the known benefits of both therapies for improving muscle function, some patients don’t reach certain motor milestones, and increasing doses may lead to harmful side effects. When low doses of risdiplam were combined with a Spinraza-like molecule, the defect in the SMN2 backup gene (that also encodes SMN, albeit in a poorly functional form) was almost completely corrected by more than a single low dose of each treatment.
No. 4 — Advocates unite for SMA Awareness Month
During August, the annual SMA Awareness Month, patients, caregivers, doctors, researchers, and other supporters came together to improve disease knowledge, patient advocacy, and research funding to help find a cure for SMA. The theme for 2024 was “Breakthroughs Begin with You,” and the month started with a candle-lighting event to remember those individuals who have died from SMA, and to honor those who make up the community. Additional activities throughout the month included fundraising walks, sharing stories, and showing off swag to boost awareness. Participants in SMA Awareness Month events were encouraged to share their photos on social media and tag @CureSMA using the hashtags #SMAwarenessmonth and #CureSMA.
No. 3 — Mortality risk in SMA drops with each month of age at onset
Survival outcomes in SMA are strongly influenced by age of onset, even among patients with the same type of the genetic disease, a study published in June reported. According to more than 30 years of data collected at a center in Thailand, the risk of mortality in children with SMA types 1 and 2 decreased significantly for every additional month at the age of onset. The study followed more than 100 children with SMA, most of whom had never received a DMT. As of the latest follow-up, about 4 of every 5 patients with type 2 were still alive, compared with 9 of 10 with type 3. Still, just 1 in 5 with SMA type 1 were alive. These data provided critical insights for genetic counseling, the researchers noted.
No. 2 — Woman in late 40s with unsteady walk diagnosed with SMA
A 47-year-old woman with a long history of muscle weakness was diagnosed with SMA when doctors noticed she walked unsteadily. The woman was seen for anemia — low numbers of red blood cells or of hemoglobin to carry oxygen to the body’s tissues — associated with chronic kidney disease, but medical records showed she had been treated with corticosteroids for many years for unspecified progressive muscle weakness. During one visit, the patient showed an unsteady walk, which prompted doctors to conduct a genetic test. That testing revealed an SMA-causing mutation in the SMN1 gene. The woman was referred for genetic counseling and informed about her condition and the risk of progression.
No. 1 — Fatty liver disease common in SMA children, adults
Fatty liver disease, the abnormal buildup of fat in the liver, was found to be common in a small group of adults and children with SMA — regardless of disease type or severity. Indeed, six of the eight SMA patients in the group showed signs of the condition. A team led by scientists in Singapore had examined clinical data from the five children and three adults, none of whom had a history of liver disease, after they had a liver ultrasound and blood tests for liver health. All were being treated or had been treated with at least one of SMA’s three approved DMTs. Ultrasound showed mild to moderate fat accumulation in the livers of six of these patients, with three showing elevated blood markers for liver damage. Patient-derived liver cells confirmed that such accumulation was caused by altered fat metabolism due to SMN1 mutations.
At SMA News Today, we hope our stories and reporting throughout 2024 positively impacted the lives of those with SMA. We wish a very happy new year to all our readers!
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