The director of the Global Centre for Excellence in ALS at the Montreal Neurological Institute, Dr. Angela Genge, has stressed that "it is important to have the genetic information of all patients" with amyotrophic lateral sclerosis "to guarantee access to clinical trials" and to have this data available "in case a new treatment targeting a specific genetic form appears."
"Even in cases where there is no family history, relevant genetic findings can occur that are useful for accessing trials or for knowing what to expect from the course of the disease," she indicated, while the biotechnology company Health in Code recalled that this "is a complex disease" in which "approximately 90 percent of cases are not hereditary and the specific cause is unknown."
However, the company specified that "it is known that in motor neurons essential cellular processes fail as a consequence of a combination of biological, genetic, and environmental factors." "Although hereditary cases are the least common, genetics gives us clues about the disease in many patients, as certain alterations are also present in cases without a family history," she added.
"In most cases of familial ALS, genetic variants associated with Mendelian forms are identified," stated the head of Neurology at this laboratory, Dr. Alba Navarro, who explained that this "accounts for 50-85 percent of patients with a family history." Even so, she remarked that "we also find these variants in 10-20 percent of cases without a family history."
Along these lines, Health in Code detailed that "for years, knowing whether an ALS patient presented genetic variants associated with the disease has served to confirm the diagnosis, guide patient follow-up, and offer family genetic counseling." "Now, genetic information also facilitates access to therapeutic options," they pointed out.
"Targeted therapies like tofersen, funded in Spain, have shown benefits in patients with variants in the SOD1 gene," they continued, highlighting that "between 2 and 3 percent of ALS patients present this genetic form of the disease associated with SOD1." "Although the percentage of patients who can benefit from this therapy is relatively low, the discovery of its effectiveness contributes greatly to research against ALS," they stated.
Determining which patients can access targeted therapies
For this company, what has been observed "is proof that it is possible to act on a specific molecular mechanism and slow down neuronal damage." In this way, "genetics no longer only helps to understand ALS, it begins to determine which patients can benefit from targeted therapies and clinical trials," they assured.
They also pointed out that "in the results of the 'VALOR' study, which support the authorization of tofersen ('Qalsody'), a functional and strength improvement has been observed in patients, as well as a reduction in neurofilaments, biomarkers that measure the level of neurodegeneration." "Now, the challenge is to transfer this process to other molecular mechanisms," they explained.
"In addition to the SOD1 gene, other clinical trials are underway to treat other genetic forms of ALS, such as that caused by the alteration of C9orf72, the most frequent, or FUS," they indicated, emphasizing that "these strategies represent a shift towards Precision Medicine in a disease until now without curative treatment."
In parallel, the International Alliance of ALS/MND Associations advocates that "all" patients should have the right to access "genetic testing, genetic counseling, and up-to-date information on clinical genetics in ALS." This is stated "in its declaration of fundamental rights of people with ALS," confirmed Health in Code, which added that "more and more international guidelines are moving in the same direction."
"Considering the existence of a targeted therapy funded in our country, as well as various ongoing clinical trials, experts recommend that genetic study be performed in all ALS patients, regardless of whether they have a family history," they reiterated, emphasizing that this analysis "allows identifying when there is a family risk and when there is not, in addition to guiding the study of other family members if necessary."