An unusual news today: Alchemab Therapeutics, a UK biopharmaceutical company, announced it has entered a collaboration with Lilly to discover novel therapeutic candidates to treat amyotrophic lateral sclerosis (ALS). There are a few similar announcements, so it means that Lilly knows that Alchemab's drug has a good chance of developing into a commercial drug. A similar partnership in the ALS field was Ionis with Biogen, which at the end provided Tofersen (Qalsody), which helped some ALS patients.
Alchemab's approach is data-oriented. Instead of trying to find molecules that are causative of a disease and to deactivate them, they search individuals with unusually slow rates of disease progression, or at risk of developing a disease but still healthy, to identify antibodies associated with resilience. Such individuals could be patients with years of survival with typically untreatable cancer, very long-lived, healthy individuals without chronic diseases, or patients with susceptibility to neurodegenerative disease that do not progress (it happens). If you want to know more about their methods, here is a link: https://www.mlsb.io/papers_2023/Enhancing_Antibody_Language_Models_with_Structural_Information.pdf
Alchemab believes these antibodies, which are not found in disease progressors, could present therapeutic opportunities. This is complicated reasoning. Why would antibodies be useful in non-transmissible diseases in general? Why not an approach like those of Ionis, which uses ASO to prevent proteins from being produced by the cell in the first place? And this is too simplistic to my taste, but apparently Lilly thinks otherwise. Alchemab deliberately uses agnostic approaches because it is not tainted by bias or misunderstanding of underlying biology.
Once data-driven approaches find an antibody candidate, it must be modified to be stable and safe for the host. Then it must be tested in pre-clinical studies on animal models, and if successful, in clinical trials involving humans.
Alchemab already has several candidate drugs in its pipeline, and there is one for ALS. The drug is named ATLX-1282, and it targets the protein UNC5C. This protein belongs to the UNC-5 family of netrin receptors. The UNC-5 family of receptors mediate the repellent response to netrin. Netrins are secreted proteins that direct axon extension and cell migration during neural development. They are bifunctional proteins that act as attractants for some cell types and as repellents for others, and these opposite actions are thought to be mediated by two classes of receptors.
So, at least there is some logical connection between the drug and the disease; this is not the case for most drugs (unsuccessfully) tested against ALS. Yet there are thousands of molecules associated with ALS, and it is not disclosed what makes UNC5C a good target in ALS. In addition, netrins apparently act during neural development, yet most ALS patients are at the opposite end of the life span.
Here are some publications on the relation between axon guidance and ALS, but it's not because some scientific publications assert something that it is necessarily true or useful.
https://pubmed.ncbi.nlm.nih.gov/24918638/
https://pubmed.ncbi.nlm.nih.gov/25177267/
https://pmc.ncbi.nlm.nih.gov/articles/PMC2175528/
The only publication I found by Alchemab about ALS and UNC5C is this one: https://www.alchemab.com/wp-content/uploads/2023/12/Society-for-Neuroscience-Posters.pdf I am not sure it proves anything about a link between ALS and UNC5C or even netrins.