RO7105705 (also known as MTAU9937A and RG6100) is an experimental immunotherapy being developed by Genentech (a subsidiary of Roche), in collaboration with AC Immune, to treat Alzheimer’s disease. The potential therapy, an antibody, is designed to target harmful forms of a protein called tau and stop its spread in the brain.
How RO7105705 works
Alzheimer’s disease is a progressive neurological disorder and the most common form of dementia. It is characterized by changes in the brain that include the formation of plaques, which are clumps of a protein called beta-amyloid that accumulate between nerve cells in the brain, and tangles, which are twisted strands of tau protein that builds up within these nerve cells.
Tau normally helps stabilize microtubules, which are cellular structures involved in molecular transport. In Alzheimer’s disease, tau proteins clump together rather than sticking to the microtubule.
Scientists do not fully understand how these plaques and tangles lead to Alzheimer’s disease, but think their formation damages brain cells and interferes with signaling between them.
Recent research indicates that the harmful tau protein tangles may spread from one part of the brain to another, suggesting that preventing the spread of tau tangles might slow disease progression.
RO7105705 is an antibody that recognizes abnormal forms of tau, and aims to block their spread from one cell to the other. Antibodies occur naturally in the body and play a role in identifying foreign objects such as bacteria and targeting them for destruction by immune cells.
Scientists are able to engineer antibodies to recognize specific targets of their choice for use in research or treatment of disease.
RO7105705 in clinical trials
A Phase 1 clinical trial (NCT02820896) tested the safety and tolerability of RO7105705, as well as its pharmacokinetics, or evaluates how a drug is processed in the body.
The double-blind study, completed in 2017, enrolled 74 people in a mix of healthy volunteers and patients with mild-to-moderate Alzheimer’s disease. They were randomized to receive one or multiple doses of RO7105705, or a placebo, either intravenously (injected into a vein) or subcutaneously (injected under the skin).
The primary outcomes were adverse events and changes in suicidal thoughts. In Alzheimer’s patients, researchers also looked for changes in cognitive function and clinical dementia scores. Levels of the RO7105705 antibody in the blood were also measured.
Trial results have not been published, but Genentech presented initial safety findings at conferences in 2017. These showed that there were no serious adverse events, with minor side effects that included bruising and pain at the injection site.
Based on these findings, Genentech began a Phase 2 clinical trial called TAURIEL (NCT03289143) in 2017. The study, expected to fully conclude in September 2022, is being conducted at 74 centers in the U.S., Australia, Canada, France, and Germany. It aimed to enroll about 360 people with mild or prodromal Alzheimer’s, a very early stage of the disease in which memory begins to decline.
RO7105705 in three different doses or a placebo is being administered intravenously in this double-blind study. Participants are being assessed for changes in dementia severity, cognitive function, and the ability to perform activities of daily living. Brain tissue health is being examined through positron emission tomography (PET) imaging.
People who complete the main study have the option of receiving RO7105705 in a 96-week, open-label extension of this trial.
Genentech opened a new Phase 2 randomized, double-blind, and placebo-controlled trial (NCT03828747) in 2019. This study is now recruiting up to 260 participants with moderate Alzheimer’s disease, confirmed either through evidence of amyloid in the cerebrospinal fluid (CSF) or a positive amyloid PET scan, at sites across the U.S., France, Poland and Spain.
This study will measure changes from baseline (study start) in functional and cognitive abilities after 49 weeks of treatment, and compare changes recorded in patients given RO7105705 to those in the placebo group. The trial is expected to be finish in September 2021, and participants have the option of continuing or starting treatment in an open-label extension study.
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