Top 10 ALS Stories of 2019
As a reminder of what mattered most to you in 2019, here are the top 10 most-read articles of last year with a brief description of what made them interesting and relevant to the ALS community.
We look forward to reporting more news to patients, family members, and caregivers dealing with ALS during 2020.
A tale of two preclinical studies showed that a gene therapy candidate targeting a key ALS mutation in the C9orf72 gene was able to lessen the buildup of toxic RNA clumps and reduce the activity of the mutated gene in cells collected from a patient with frontotemporal dementia (FTD) and a mouse model of ALS.
Developed by uniQure, the therapy is designed to silence the disease-causing gene. It works by delivering microRNAs (miRNAs) — RNA molecules that regulate gene expression — that target the mutated C9orf72‘s RNA for degradation. The results supported the continuation of uniQure’s gene therapy program in ALS and FTD, the company said.
In the summer, a small study discovered an altered composition of gut microbes in people with ALS, which could drive digestive problems in those with the disease.
Using genetics, a research team in China found that fecal samples of people with ALS have an increase in harmful microbes of the phylum Firmicutes and a decrease in beneficial microorganisms called Bacteroidetes. The resulting poor gastrointestinal health may lead to a decline in the gut’s digestion and metabolism functions.
At the beginning of the year, U.S. biopharmaceutical MediciNova received a notice of allowance stating that its request for a patent covering a combination of its investigational therapy ibudilast (MN-166) plus Rilutek (riluzole) was being considered by the U.S. Patent and Trademark Office.
Ibudilast is a small molecule that reduces the activity of immune cells in the brain while supporting the growth of motor neurons, those lost in people with ALS. In a Phase 2 trial (NCT02238626), the treatment was found to work well in combination with Sanofi‘s approved therapy Rilutek, improving patients’ functional activity, quality of life, and muscle strength.
The notice of allowance was the final step toward patent registration. Such registration will provide patent protection until November 2035 to the combination, for use in treating ALS and other neurodegenerative diseases.
In June, MediciNova launched a Phase 2b/3 clinical trial to continue studying ibudilast as an add-on therapy to Rilutek. The multicenter, double-blind study (NCT04057898) will recruit approximately 230 participants, who will be randomly selected to receive either ibudilast plus Rilutek or a placebo plus Rilutek for 12 months.
The trial’s main goal is to study ibudilast’s impact on ALS progression and functional disability by determining changes in the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score between the beginning and end of the treatment period. Secondary objectives include changes in patients’ muscle strength, quality of life, and respiratory function. The study also will evaluate the safety and tolerability profile of ibudilast.
Just a few months earlier, MediciNova had received approval from the U.S. Food and Drug Administration (FDA) to initiate this trial. Eligible patients must have had the disease for no more than 18 months and present just mild disability.
During the trial, patients will receive Rilutek for at least 30 days before starting a regimen of either 100 mg per day of ibudilast or a placebo for a period of 12 months. Participants may then enter an extension phase in which they will be offered the ibudilast combination for an additional six months. Top-line data is expected by December 2021.
The Phase 3 trial evaluating BrainStorm Cell Therapeutics‘s cell therapy candidate NurOwn completed patient enrollment in October. The 200 participants will receive three administrations of NurOwn, or a placebo, into the spinal canal every two months. The primary goals are to demonstrate the therapy’s safety and its ability to slow disease progression.
A cell-based therapy, NurOwn works by removing specific stem cells from patients and converting them to cells that produce molecules that promote nerve tissue growth and survival. The modified cells are then returned to the patient to stimulate nerve tissue growth. NurOwn aims to safely improve abilities like swallowing, speech, handwriting, and walking in people with ALS.
A long-term Phase 2/3 study examining vitamin B12 as a treatment for ALS found that ultra-high doses of methylcobalamin, the physiologically active form of this vitamin, may extend survival and slow the decline in functional capacity, compared with a placebo.
The study included 373 patients, diagnosed fewer than three years earlier, across 51 sites in Japan. However, the benefits were only seen in patients diagnosed less than one year before taking the supplements, and only a trend was observed.
Results from a Phase 1 clinical trial (NCT02870634) showed that CuATSM — a small molecule able to selectively deliver copper to cells with damaged mitochondria — slowed disease progression and improved the respiratory and cognitive function of people with ALS.
Damaged mitochondria are considered a hallmark of several neurodegenerative diseases, including ALS, and delivering copper is thought to restore the health of these organelles. Developer Collaborative Medicinal Development (CMD) began testing CuATSM in patients with sporadic and familial ALS in 2016. CMD is now planning to launch a randomized, placebo-controlled clinical trial for CuATSM to confirm these results.
In March, a study discovered several species of bacteria and fungi living in the central nervous system (CNS) of people with ALS, suggesting that patients have coexisting bacterial and fungal infections.
The study built on prior research suggesting that ALS might be caused by a fungal infection. Researchers then examined frozen CNS tissue from 11 ALS patients to assess whether bacterial infections accompany fungal infections. Bacterial DNA was found in different regions of the CNS and the presence of bacteria was confirmed in neural tissue samples.
Our most-read article of 2019 reported that small nerve damage may serve as an ALS trigger. Such damage may accelerate motor symptoms in rats carrying a mutation in the SOD1 gene, one of the 40 genes associated with ALS development in humans.
While rats without the mutation completely recovered leg function four weeks after induced damage to the sciatic nerve, located in the leg, SOD1-mutated animals were unable to fully recover. These rats also lost function in the uninjured leg, likely as a consequence of sustained immune activation and more severe neurodegeneration.
The induced nerve damage mimics head injury and trauma in human patients, which could explain the higher prevalence of the disease among war veterans and professional athletes.
At ALS News Today, we hope these stories and our regular reporting throughout 2020 contribute to informing and improving the lives of everyone affected by ALS.
We wish all our readers a happy 2020.