How does ATA188 work?
MS is a neurodegenerative disorder characterized by the immune system mistakenly attacking the myelin sheath. The myelin sheath is the protective coating that surrounds the nerves. Without this protective coating, nerve cells become fragile and are easily damaged. This leads to neurodegeneration (death) of nerve cells.
One cause of MS may be the Epstein-Barr virus (EBV). This virus infects B-cells (a type of immune cell that produces antibodies). The antibodies that EBV-infected cells produce are much more likely to be autoreactive, meaning they erroneously attack the body’s own cells and tissues. Researchers think that people with MS also have fewer T-cells (another type of immune cell). This, in combination with an EBV infection, could contribute to the development of MS.
ATA188 consists of EBV T-cells that selectively identify and destroy EBV-infected cells. This could reduce the antibodies that those cells produce against the myelin sheath. Ultimately, it could slow or halt disease progression.
ATA188 in clinical trials
A Phase 1 clinical trial in Australia (ACTRN12615000422527) tested the safety and tolerability of ATA188 in patients with primary and secondary progressive MS. Of the 13 recruited patients, 10 received the full course of treatment with ATA188. Seven patients showed improvements. Six of them demonstrated both symptomatic and objective neurological improvements together with a reduction in fatigue and an improved quality of life. There was a reduction in autoantibodies in the fluid that surrounds the brain and spinal cord of three patients. There were no reports of serious side effects due to the treatment.
Ongoing clinical trials
A Phase 1a/1b clinical trial (NCT03283826) is recruiting patients with relapsing-remitting MS and progressive MS in the U.S. and Australia. The study consists of two parts. The first part aimed to determine the safety and tolerability of ATA188, as well as, the best dose to be used in part 2. In part 1, 25 patients received one of four doses of ATA188 — 5 million, 10 million, 20 million, or 40 million cells — to determine which had the best safety and effectiveness profile. Patients received two cycles with three intravenous (IV) injections in each. Researchers then evaluated them three, six, and 12 months after the last treatment. After this initial round of testing, patients have the option to continue receiving treatment once a year for four years.
Researchers presented the results of the first part of the trial at the MSVirtual2020 meeting. They showed that the participants in all dosage groups tolerated the treatment well. They also showed a dose-related increase in the number of patients who achieved sustained disability improvement (SDI) in each group (4% at the lowest dose, 17% at the next dose, and 42% at the second-highest dose). Data from the highest dose are not yet available.
The trial has begun recruiting up to another 72 patients for its second part. Researchers will randomize an initial group of 36 patients 5:4 to either receive a dose of 20 million cells or a placebo. Depending on the results, they may enroll the other 36 patients and randomize them 2:1 between treatment and placebo groups. Patients will receive two cycles of treatment or a placebo.
Researchers will follow them for 12 months after the first dose. In the second year of the study, patients who received a placebo in the first year will receive two cycles of treatment. Those who received treatment in the first year will receive one cycle of treatment and one cycle of placebo in random order. Patients who complete the second year of study can enroll in an open-label extension study for up to three more years.
Researchers expect to complete the study in 2026.
Last updated: Oct. 23, 2020
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