Experimental Treatments for ALS

AstroRx is a stem cell therapy comprised of fully matured human astrocytes derived from human embryonic stem cells, given by intrathecal (into the fluid surrounding the spinal cord) injection to support damaged motor neurons. Treatment is aimed at compensating for the malfunctioning astrocytes and help to prevent the loss of motor neurons, slowing ALS progression. The potential therapy has completed a Phase 1/2 trial.

Cannabis-derived products are being evaluated for their potential in treating ALS in various clinical trials. The active ingredients in cannabis — tetrahydrocannabinol (THC) and cannabidiol (CBD) — are called cannabinoids. They are believed to work as antioxidants and as anti-inflammatory and neuroprotective agents and thus might be able to slow or prevent further damage to nerve cells in ALS.

CNM-Au8 is an experimental therapy being developed to treat patients with ALS, Parkinson’s disease, and multiple sclerosis. It contains a suspension of nanocrystalline gold that acts to support biological reactions within cells that generate energy, as well as help remove the destructive byproducts of cellular metabolism. Preclinical studies have demonstrated that CNM-Au8 is able to protect motor neurons from severe damage and death. It is being studied in Phase 2 trials.

CNS10-NPC-GDNF is an experimental stem cell-based therapy. It is a type of stem cell called a human neural progenitor cell that has been genetically engineered to produce GDNF. It is hoped that when transplanted into the spinal cord of the patients, the cells will grow into astrocytes and provide GDNF to motor neurons. This approach may increase the survival of motor neurons, improving motor function and delaying disease progression. It has completed a Phase 1 trial in ALS patients.

Engensis (VM202) is a DNA-based gene therapy carrying the instructions to produce more of a protein called hepatocyte growth factor (HGF), which aids in the formation of new blood vessels, prevents muscle atrophy (shrinkage), and participates in the growth and survival of nerve cells. By boosting HGF production, Engensis may help lessen the progressive loss of motor control that characterizes ALS. A Phase 2a trial is currently recruiting ALS patients.

GM6 is an artificially created peptide being developed for the treatment of ALS and other neurodegenerative diseases. In contrast to other therapies, GM6 does not have a distinct target, but rather affects multiple pathways to treat ALS and promote motor neuron survival by slowing degeneration through an unknown mechanism. It has completed Phase 2 trials in ALS patients. 

IPL344 is an experimental treatment being developed to slow ALS progression. IPL344 is a molecule that researchers designed to activate the Akt signaling pathway, which plays a role in the survival of cells. Studies have shown that the activity of the Akt pathway is reduced in patients with ALS. By activating the pathway, researchers think IPL344 may help protect nerve cells and slow the progression of the disease. A Phase 1 trial is currently recruiting ALS patients.

Masitinib is an experimental oral tyrosine kinase inhibitor that targets cells of the immune system called the mast cells and macrophages. It works by blocking the activation of proteins called tyrosine kinases, which play a role in inflammation and chronic inflammatory states. A Phase 3 trial testing masitinib as an add-on therapy is currently recruiting ALS patients.

MN-166 is a small molecule that inhibits the action of enzymes called phosphodiesterase -4 and -10 and that of macrophage migration inhibitory factor, which all play important roles in inflammation. MN-166 also blocks the activity of cell signaling molecules that play a role in inflammation, promoting the survival, development, and function of nerve cells. A Phase 2/3 trial is currently recruiting ALS patients. 

NSI-566 is an experimental stem cell-based therapy aimed at decreasing motor neuron loss and improving motor function in ALS patients. It consists of human spinal cord-derived neural stem cells, when injected into the spinal cord, differentiate into mature neurons. They surround and support the impaired motor neurons in ALS by integrating into the neural network and forming connections (synapses) with the patient’s own neurons. A Phase 3 trial is being planned.

NPT520-34 is an investigational oral small molecule that can penetrate the blood-brain barrier. It is able to reduce the production of proteins associated with astrocytes and microglia. In this way, the potential therapy may slow down ALS disease progression by reducing neuroinflammation. The potential therapy has completed a Phase 1 trial in healthy volunteers with positive results.

NT0502 is an experimental oral treatment being developed to reduce excessive salivation — drooling — a common problem in patients with ALS. The small molecule contained in NT0502 is an inhibitor that binds to the receptor to which acetylcholine would normally bind. By blocking this receptor (called a muscarinic receptor), NT0502 reduces the amount of saliva that is produced and secreted by the salivary glands. The potential therapy has completed a Phase 1 trial.

NurOwn is an investigational therapy that uses a mesenchymal stem cell (MSC) platform to treat ALS. Using MSCs harvested from the patients themselves, it is aimed at helping nerve cells survive by fighting the neurodegeneration process. NurOwn’s technology encourages MSCs to develop into cells that secrete neurotrophic factors, which promote the growth of nervous tissue and also can help nerve cells survive through their own neuroprotective function.

Pridopidine is an investigational sigma-1 receptor agonist for ALS treatment. It is a small molecule that binds to the sigma-1 receptor on nerve and glial cells, which are the cells that support nerve cells. Scientists think that the sigma-1 receptor may play a role in protecting the nervous system against neurodegenerative diseases, including ALS. A Phase 2/3 trial is currently enrolling by invitation.

Tegoprubart is an antibody-based therapy designed to suppress neuroinflammation by preventing the interaction of two molecules — the CD40 ligand (CD40L) and its receptor — at the surface of multiple types of immune cells. This pathway is overactive in ALS patients and can contribute to inflammatory nerve damage. A Phase 2 trial investigating tegoprubart is now complete.

Cell therapy using regulatory T-cells (Tregs) has shown promise in suppressing inflammation and slowing the progression of ALS. Scientists think there is an inverse link between levels of Tregs and the rate of ALS progression. This suggests that enhancing the Tregs level in people with ALS could delay the disease’s progression. The potential therapy is being investigated in a number of trials.

TUDCA (tauroursodeoxycholic acid) is a small molecule that may be able to decrease nerve cell death, a hallmark of ALS, through its ability to act as an antioxidant that prevents toxic reactive oxygen species from accumulating inside cells. The molecule also has the ability to control immune function. It is currently being studied as an add-on treatment in Phase 2 and 3 trials.

Ultomiris contains an antibody that is injected into the bloodstream and that inhibits a protein called C5, a member of the complement system, which is thought to be implicated in neurodegeneration in ALS. By inhibiting C5, Ultomiris interrupts the overreaction of the complement system, potentially slowing ALS progression. It is currently being tested in Phase 3 trials in ALS patients.