At the most basic level, a drug is defined as “a medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body.” There are many different substances that can be used in the treatment of diseases, from herbal remedies to synthesized chemicals to repurposed cells taken from a patient’s own body.

As an extremely complex, diverse, and still incompletely understood disease, researchers must try to treat ALS from many different angles, addressing many different potential drug targets. What follows is a basic guide to some of the more common types of drugs in the ALS pipeline today, as well as a guide to treatments currently in clinical trials for ALS in each category.

Small Molecules Drugs

A very common type of therapy in many different diseases, a small molecule drug simply describes an organic compound with a low molecular weight, often synthesized in a lab. These small compounds are often able to enter cells more easily than larger molecules. As these smaller molecules are often chemically simpler than larger, more complex compounds like biologics and peptides, they are often easier to synthesize and thus cheaper to produce. There are a large variety of small molecule drugs, with many different mechanisms of actions for many different diseases. The majority of drugs currently on the market for all conditions are represented by this category.

Small Molecule Drugs in ALS Trials: masitinib, oral edaravone, reldesemtiv, ibudilast

Large Molecule Drugs/Biologics and Peptides Drugs

Biologics are treatments that are derived from a living organism. They may be harvested directly from a living organism or grown in a laboratory. They are much more chemically complex that small molecule drugs – and thus are very difficult, or, at times, impossible, to produce synthetically. Vaccines, stem cell treatments, and monoclonal antibodies are all forms of biologics. Drugs that stimulate the body’s own immune responses to fight diseases, such as immunotherapies in cancer treatment, are also considered biologics. Peptides fall in between biologics and small molecule drugs – they are complex compounds, but are slightly smaller and simpler than biologics, and can sometime be synthesized in a lab. Insulin for diabetes is a common example of a peptide treatment.

Biologics/Peptides in ALS Trials: AT-1501 (tegoprubart), pegcetacoplan, ANX005, AP-101

Cellular Therapies

Also known as autologous cell therapies, cellular treatments involve taking a person’s own cells, processing them in some way, and reintroducing them to the body. In ALS, there are a number of treatments in various stages of development utilizing cells from the immune system and stem cells, the basic building blocks of the body that can be differentiated into many different kinds of cells.

Cellular Therapies in ALS Trials: Adipose-derived mesenchymal stem cells, Rapa-501

Antisense Oligonucleotides (ASO)

ASOs are small single-stranded molecules of DNA that are easily absorbed by cells, where they attach themselves to “messenger” mRNA strands. They can then, in effect, “turn down” a gene, disrupting the cell’s natural production of a particular protein. This is useful in treating genetic conditions, where mutations in DNA can cause cells to produce harmful proteins or prevent them from producing those that our body needs to function.

ASOs in in ALS Trials: BIIB105, WVE-004, BIIB067, ION363

Gene Therapy

Gene therapy is a therapeutic approach that seeks to modify or correct the underlying genetic causes behind a disease. Gene therapies can work in several different ways, including replacing a disease-causing gene in cells, “turning off” a disease-causing gene, or introducing a new gene into cells to help fight a disease. There are many different ways that gene therapies introduce or modify genes in the body, including through directly inserting DNA molecules into cells, using modified bacteria or viruses to introduce modified genes, or utilizing gene editing technologies such as CRISPR. ASOs and certain cellular treatments may also be considered types of gene therapies.

Gene therapies in ALS Trials: upcoming clinical trial APB-101

ALS TDI: The Drug Discovery Engine for ALS

There are many drugs of each type described in this article in varying stages of development across the ALS space. However, even though the ALS drug pipeline is more promising than ever before, it will likely still not be enough. Because of the disease’s complexity and heterogeneity, it will almost certainly take many different drugs, of many different types, to ultimately end the disease.

At the ALS Therapy Development Institute (ALS TDI), our mission is to be the Drug Discovery Engine for ALS. We do this by researching new treatments in our lab – the largest drug discovery lab in the world dedicated solely to ALS. We also conduct research to make all clinical trials faster and more efficient and validate the research of others in the industry to help move forward promising treatments. Most importantly, we will not stop until there are treatments for every person living with ALS.

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