summary: Researchers have made a major advance in ALS treatment using a new gene therapy, significantly slowing disease progression in patients with aggressive ALS. Patients who have been treated since early 2020 have maintained many of their physical and social abilities and are exceeding typical life expectancy and functional expectations for their condition.
This treatment targets the SOD1 gene mutation, reducing levels of the harmful protein and stabilizing the patient’s condition. This discovery offers hope for future advances in ALS treatment and broader applications of gene therapy.
Important facts:
- effective gene therapy: This treatment significantly reduces the levels of the SOD1 protein associated with ALS, thereby slowing the progression of the disease.
- Outstanding patient outcomes: Four years after diagnosis, patients continue to perform daily activities independently, a rare accomplishment for patients with advanced ALS.
- FDA and EMA approval: This drug has been approved by the FDA and recommended by the EMA for use in patients with SOD1 gene mutations, demonstrating its efficacy and potential.
sauce: Umeå University
A breakthrough has been made in research into the disease amyotrophic lateral sclerosis (ALS).
Scientists at Umeå University report that the use of a new gene therapy has significantly slowed the progression of the disease in patients with particularly aggressive forms of ALS.
After 4 years of medication, patients are still able to climb stairs, get up from chairs, eat well, talk well, and lead an active and socially fulfilling life.
“We believe this is a breakthrough in the research we have been conducting here at Umeå University and Northern Sweden University Hospital for over 30 years. “I have never seen such a good result,” says Peter Andersen, a neurologist and professor at the Faculty of Clinical Sciences at Umeå University.
“The key finding is that we were able to significantly reduce the levels of the disease-causing SOD1 protein and at the same time measure a clear suppressive effect on further progression of the disease.
“When we diagnosed the patient in the neurology ward in early spring of 2020, the patient’s prognosis was at most 1.5 to 2 years of survival. The patient far exceeded expectations.”
The patient comes from a family in southern Sweden with a particularly aggressive form of ALS disease caused by mutations in the SOD1 gene. When a relative of hers was diagnosed with ALS, the patient left a blood sample with her ALS research team at Umeå University for research purposes, but chose not to learn about the results of the genetic test.
However, the patient carries the gene for the disease and realized he too had the disease after experiencing muscle weakness four years ago. The patient was immediately admitted to the medical team at Northern Sweden University Hospital and diagnosed with early stage ALS disease.
Since summer 2020, the patient has been participating in a Phase III study evaluating a new gene therapy developed for patients with SOD1 mutations that cause the SOD1 protein to misfold and aggregate in motor neurons.
Patients received the experimental treatment every four weeks at a university hospital in Copenhagen, Denmark.
Biomarkers reduced by almost 90%
At the time of diagnosis in 2020, the patient had extremely high levels of a substance called neurofilament L, a biomarker that indicates nerve cell destruction. Now, four years later, that level has fallen by almost 90%.
“When the patient was diagnosed at a university hospital in northern Sweden in April 2020, we measured neurofilament L levels, which were as high as 11,000 nanograms per liter, one of the highest in ALS patients.
“In the latest samples, after 50 injections of the new drug, the levels dropped from 1,200 to 1,290, which is a significant drop in disease indicators,” says Peter Andersen.
“The normal level for someone in the patient’s age group is below 560. The level of neurofilaments in the blood has returned to normal levels and was down to 12 at the most recent visit.” The normal level is below 13. ”
The patient’s level of functioning, measured using the ALSFRSR scale, has decreased compared to healthy individuals (48 points), but has remained at approximately the same level (approximately 35-37 points) over the past 18 months . This means that the patient’s level of functioning is reduced. This is approximately 26% lower than in healthy people.
Patients with this progressive type of ALS gene mutation typically lose 1 to 1.5 points per month. This means that without treatment, the expected disease progression would have been very rapid, resulting in significant disability within 6 to 12 months and possibly leading to the patient’s death in 2021.
“It’s kind of a miracle that this patient is still able to climb stairs, more or less without any problems, four years after the onset of symptoms,” said Dr. Peter Andersen, a neurologist and researcher in the Department of Clinical Sciences. says Dr. Karin Forsberg. He has been researching SOD1 and ALS for over 20 years.
“Such success with drug treatment is a great success and inspiring. But it by no means means the work is done. This is just the beginning.
“It’s also important to remember that while the drug in question is not a curative cure, it appears to be able to put a brake on the progression of the disease. This gives great hope for further development of drug treatments for ALS patients.” will give you.”
Although there are many types of ALS disease, only 2% to 6% of ALS diseases are caused by mutations in the SOD1 gene. Although the disease is mostly familial, mutations in SOD1 have also been found in so-called sporadic ALS cases.
“It is currently unknown whether this drug has a similar effect on other types of ALS disease. Much more research is needed on this topic,” says Peter Andersen.
Patients can still do almost everything they were able to do when they first entered the study in the summer of 2020. His language is unaffected and he is able to do everything on his own, including mowing the lawn, shopping, and taking care of children. The kids. I feel much better mentally, mainly because I now feel more hopeful.
‘This is just the beginning’
The study in which this patient is participating will conclude this summer. The drug is not yet available in Sweden, but it has been approved by the US Food and Drug Administration (FDA), and on February 23, 2024, the European Medicines Agency (EMA) will ban the use of the drug in patients carrying the SOD1 gene. Recommended. Variations within the European Union.
However, Sweden’s Council for New Therapies has asked local health care providers not to prescribe the drug until a health economic evaluation is carried out by the Dental and Pharmaceutical Benefits Agency.
“Our next step is to study the outcomes of patients who received this drug. While it worked for some, not everyone experienced the same positive effects. It may be a matter of dosage or the stage of the disease at which treatment is started.
“Could additional drugs be needed to completely stop the process? These are the questions we must now challenge and answer. This is just the beginning” Karin Fors Berg says.
She envisions a future where treatment is based on the type of ALS disease a patient has, perhaps requiring a combination of drugs.
She said a lot of research is being done in Sweden and internationally to find new drug targets so that comparable drugs can be developed for other types of ALS patient groups, and that will become a reality. He emphasized that he is looking forward to it.
“From samples taken from patients, we can measure that disease progression is underway, but it appears that the patient’s body is able to compensate. Still four years later.
The Swedish Ethical Review Authority approved our participation in these studies, and now, several years later, we and ALS doctors from other participating countries have confirmed clear clinical effects in many treated patients. ” says Peter Andersen.
“The next step is to obtain approval from the Swedish Ethical Review Authority to study the compensatory mechanisms that treatment with this drug appears to activate. There may be opportunities to gain insight into how drugs work and develop new and better drugs.”
About this ALS and gene therapy research news
author: peter andersen
sauce: Umeå University
contact: Peter Andersen – Umeå University
Image: Image credited to Neuroscience News
Original research: The findings appear below e-life.
