💉 New drug slows ALS

• The drug Tofersen shows good results for patients with ALS caused by mutations in the SOD1 gene, which accounts for 5-6 percent of all ALS cases.
• Several patients have experienced significant slowing of disease progression, and in some cases the disease has stabilized at the same level.
• A preventive study called ATLAS is ongoing at Umeå University for healthy individuals who carry SOD1 mutations with a high risk of developing ALS.

How Tofersen works

Tofersen is a medication administered through monthly injections directly into the spinal fluid. It works by reducing the production of the disease-causing SOD1 protein.

"Tofersen works by attaching like a padlock to the gene and preventing the disease-causing protein from forming," explains Peter Andersen, senior physician in neurology and professor at the Department of Clinical Science at Umeå University.

Brain Foundation donors have supported Andersen's research since 1998, including co-financing the clinical trials of Tofersen in Sweden.

Different mutations cause different disease progression

There are 16 different locations on the SOD1 gene where mutations can cause various types of ALS disease. Research is ongoing to determine if Tofersen is effective against all these variants.

A Swedish patient named Niklas, whose ALS has been halted by Tofersen, carries the A4S mutation variant, which typically leads to rapid disease progression.

"When he contacted us in January 2020 with early symptoms, it was very important that we could conduct a quick investigation and include him in the phase III study of Tofersen, the VALOR study. We knew from the phase II study that it seems to have the best effect when introduced early," says Andersen.

According to Andersen, Tofersen has also been tested on patients who have had ALS for several years with demonstrable effect. No patient in Sweden has been cured by the medication, but many have experienced a significant slowing of the disease. In several patients, the disease has stabilized at approximately the same level.

Mapping genetic factors

A large part of Andersen's work involves building a biobank with blood samples from 17,000 patients and their relatives. Through this mapping, researchers can study how the disease progresses and how strongly the disease-causing gene manifests.

Some mutations in the SOD1 gene, such as D109Y, can be carried without the person becoming ill. Others, like the A4S that Niklas carries, lead with 100 percent certainty to the carrier developing ALS. Some gene variants lead to an aggressive disease course with death within one to two years, while others, like the most common variant D90A, involve a slower disease progression over several years.

Preventive treatment under development

The ATLAS study, conducted in Umeå, is the first study in the world aimed at preventing the onset of ALS. Healthy individuals who are carriers of SOD1 with a 100 percent risk of developing ALS can participate if they qualify, and receive Tofersen as a preventive measure. The study is co-financed by the Swedish Brain Foundation.

Tofersen belongs to a category of drugs called antisense oligonucleotides (ASO). These are synthetic DNA or RNA strands that bind to mRNA to block protein production or affect gene expression. Researchers are now working to develop similar substances that can target other known ALS genes.

The results from the Tofersen studies show that it is possible to treat ALS. Researchers can directly measure the drug's effect on SOD1 in the spinal fluid and monitor the patient's muscle strength, respiratory capacity, and well-being. This success is driving the development of new drugs for SOD1-ALS and other types of ALS diseases.

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