An injection of IONIS-MAPTRx resulted in a 70 percent decrease in tau protein produced in the brains of non-human primates, researchers at Ionis Pharmaceuticals, the potential treatment’s maker, are reporting.
These positive pre-clinical findings helped in the design of a first clinical study, now underway and enrolling, that will assess IONIS-MAPTRx in people with mild Alzheimer’s disease.
The results are in the oral presentation “Design of the First-in-Human Study of IONIS-MAPTRx, a Tau-lowering Antisense Oligonucleotide, in Patients With Alzheimer Disease” set to be given April 22 at the 2018 American Academy of Neurology (AAN) Annual Meeting, which runs April 21—27 in Los Angeles.
In preclinical studies, in which Ionis researchers tested IONIS-MAPTRx’s safety, pharmacokinetic (the movement of the drug once inside the body) and pharmacodynamic (the therapy’s effects on the body) profiles in rodents and non-human primates.
IONIS-MAPTRx is an antisense oligonucleotide (ASO) that targets a messenger RNA molecule — called MAPT mRNA — that carries information coded by our DNA to ultimately produce a functional tau protein. As a result, IONIS-MAPTRx is designed to reduce production of the tau protein, whose accumulation and misfolding in the brain is a hallmark of neurodegenerative diseases known as tauopathies, including Alzheimer’s disease.
In non-human primates, an intrathecal injection (directly into the spinal canal) of IONIS-MAPTRx resulted in a reduction of 77% and 74% of MAPT mRNA in the brain’s frontal cortex and hippocampus, respectively. Importantly, researchers found no evidence of dose-limiting side effects.
The frontal cortex is the brain area responsible for controlling cognitive behavior, personality expression, decision-making abilities, and moderating social behavior.
The hippocampus, embedded deep in the brain, is important for learning and memory, and is also part of the limbic system, which is associated with the functions of feeling and reacting.
The trial, which will take place in at sites in Canada and five European countries, will be a three-month randomized, placebo-controlled, dose-escalation study. It will cover the safety, characteristics and behavior of IONIS-MAPTRx, and patients’ ability to tolerate it. About 44 patients are expected to take part in the trial; enrollment information is available here.
IONIS-MAPTRx will be injected once a month into participants’ cerebral spinal fluid. Researchers will also measure the therapy’s effect in cerebrospinal fluid biomarkers, neuroimaging, and patients’ clinical outcomes.
The study’s estimated completion date is February 2020.