In PHASE 2 – Ezogabine, Mexiletine, Gilenya, Rasagiline, AT-1501, Pimozide, BLZ945, RNS60, Inosine, Reldesemtiv, Zilucoplan, CNM-Au8, Nurtec, Colchicine, DNL747, Amx0035, Biotin, BIIB078

• Gilenya traps the immune cells in the lymph nodes and thus reduced unnecessary neuroinflammation.
• Preclinical trials in mouse models of ALS demonstrated that Gilenya is able to significantly extend survival and improve symptoms.
• A Phase 2a clinical trial (NCT01786174) investigating the safety and tolerability of Gilenya compared to a placebo in patient with ALS has been completed.

• Pimozide is a FDA approved neuroleptic drug used to treat psychosis, Tourette syndrome, and resistant tics.
• Enhances communication in NMJ.
• Phase I study showed that after only six weeks of treatment, patients were able to retain the control of the thenar muscles.

• Induces reduction of microglia.
• Increased oligodendrocytes and astrogliogenesis.
• Induces brain region – specific enhancement of neuronal remyelination.

• Rationale: increase urate levels by administering precursor inosine.
• A small pilot study with 25 ALS patients over 12 weeks of follow up reported that inosine is safe.
• Several markers of oxidative stress favourably changed from baseline levels.
• An ongoing phase 2 trial is testing its efficacy (NCT03168711).

• A small peptide that binds to key players of the complement cascade with high affinity and specificity (C5 and C5b).
• Complement inhibition addresses tissue damage in generalized myasthenia gravis.

• It is a beta2 adrenergic agonist.
• It has an anabolic effect on skeletal muscles.
• It also stimulates the beta adrenoreceptors in the CNS leading to increase Neurotrophic growth factor (NGF).
• It has shown neuroprotective effect on animal models.

• New formulation of Riluzole.
• Sublingual treatment: It is placed under the tongue, where it will dissolve and be absorbed quickly.
• More predictable treatment levels in the body.

• Enhances the expression of HSPB8 and of several autophagy players.
• Blocks TDP – 43 accumulation in neurons.
• Has an anti – inflammatory effect.

• Overactive RIPK1 protein is involved in excess inflammation and cell death in the brain.
• DNL747 inhibits RIPK1 protein.

• Low biotin levels cause oligodendrocyte and axonal degeneration.
• Treatment with Biotin prevents motor neuron degeneration by preserving oligodendrocytes.
• Pilot study results show that Biotin is safe.

• Studies suspended due to increased incidence of pneumonia among ALS patients receiving H.P. Acthar Gel.

• Monoamine oxidase B inhibitor, mitochondrial stabilizer already approved for the treatment of Parkinson’s Disease.

Results: The average 12 months ALSFRS-R slope between rasagiline and the mixed placebo and historical control cohorts did not show any differences. Urine and blood biomarkers did not show any benefits. Rasagiline was well tolerated and no serious adverse events noted.

• NP001 was an injected therapy that was being developed by Neuraltus to slow or stop the progression of ALS.
• The molecule was designed to calm down immune cells of the CNS- microglia – and turn them into anti-inflammatory code

Study suspended due to failed trial results

• Lowers the accumulation of toxic RNA clumps.
• Reduces the activity of this mutated gene.