ALS: There is a new therapy for patients with specific genetic mutations

A therapy capable of reducing the progression of a specific form of amyotrophic lateral sclerosis (or ALS): this is what emerges from a phase 3 clinical study recently published in the New England Journal of Medicine, which involved several international research centers, including the Molinette hospital in Turin. The drug protagonist of the study is called Tofersenis produced by the biotech company Biogen and consists of a molecule capable of selectively block the gene responsible for a genetic form of ALS. According to the article, the patients who underwent the treatment showed a slowdown in the decline of functions clinical, respiratory, muscle strength and quality of life typical of ALS.

What is ALS

Also known as Lou Gehring’s disease, Charcot’s disease or motor neuron disease, ALS is a disease neurodegenerative affecting motor neuronsthe cells of the nervous system contained in the brain and spinal cord that transmit motor signals and allow the movements of voluntary muscles, leading to a progressive deterioration in the ability to control muscles. Symptoms of ALS vary greatly from person to person, but the disease typically starts with one poor muscle strengthwhich worsens over time: neurodegeneration often begins in the motor neurons of the limbs and then it spreads to other parts of the body; as the disease progresses and nerve cells are destroyed, the muscles they get weaker and weaker, to the point of compromising walking, chewing, swallowing, speaking and breathing. The average life expectancy for people with ALS is three to five years from the onset of symptoms and, at present, there is no cure for this disease.

According to the Italian Amyotrophic Sclerosis Association (Aisla), in Western countries there are 10 sick people per 100,000 inhabitants and in Italy there are about 6,000 people with ALS. Despite the efforts of scientific research, the causes of the disease are mostly unknownalthough in recent years the role of genetics in the onset of the disease, both as a predisposing factor together with other environmental factors, and as a primary cause in some genetic forms of ALS. Numerous studies have found mutations in more than forty genes associated with the disease, but the most frequent are those related to Sod1 gene, responsible for the production of an antioxidant enzyme, essential for the body. In particular, the mutations in the Sod1 gene are responsible for about 2% of all ALS cases globally.

I study

In fact, Tofersen’s goal is Sod1, in particular the form of the gene that carries the mutation associated with the neurodegenerative disease. The drug, in fact, is a antisense oligonucleotide, that is a molecule that binds in a specific way to the messenger RNA (the molecule that has the purpose of carrying the instructions for the production of the enzyme) of Sod1, blocking it and guiding its degradation. In this way, the drug would prevent the production and accumulation of the protein associated with this form of ALS. To evaluate whether this mechanism could show beneficial effects at a clinical level, researchers from different centers selected 108 patients with ALS due to the Sod1 mutation, of which 72 received the drug through lumbar puncture and the remaining the drug placebo, and then studied the effects. at 28 and 52 weeks of dosing.

Although, as stated in the article, the drug did not reach the primary objective of the study (a change, at the twenty-eighth week, of the score of the Als Functional Rating Scale-Revised, the most used functional evaluation scale in the therapeutic protocols of the Sla), i resultsespecially one year after administration, they look promising: the researchers found one reduction in the amount of enzyme defective in the cerebrospinal fluid, a reduction in the level of molecules indicating neurodegeneration and slowing the decline in patients’ clinical function, respiratory function, muscle strength and quality of life.