IONIS-MAPTRx is aimed at reducing the production of tau protein, whose accumulation in the brain is a hallmark of the disease. The trial will evaluate the therapy in patients with mild forms of Alzheimer’s.
Therapies targeting clusters of a toxic form of tau could prove a valuable way to treat Alzheimer’s, according to a study published in February. The article, “Tau Reduction Prevents Neuronal Loss And Reverses Pathological Tau Deposition And Seeding In Mice With Tauopathy,” appeared in the journal Science Translational Medicine i
Tau misfolding leads to an accumulation of toxic tangles inside brain cells. The tangles are a key feature of neurodegenerative diseases known as tauopathies. They include Alzheimer’s and some forms of frontotemporal dementia, a rare early-onset disease that can result from neuronal damage to the brain’s frontal and temporal lobes.
“In contrast to amyloid plaques that may begin to deposit in the brain for up to 20 years before the onset of AD [Alzheimer’s], tau deposits are spatially and temporally associated with the brain regions where atrophy occurs and neurocognitive deficits originate,” C. Frank Bennett, Ionis’ senior vice president of research, said in a press release. “IONIS-MAPTRx is designed to reduce the production of all of the many forms of tau in all regions of the brain.”
The trial (NCT03186989) 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.
IONIS-MAPTRx will be injected once a month into participants’ cerebral spinal fluid.
“IONIS-MAPTRx is another exciting program within our strategic collaboration with Biogen,” said B. Lynne Parshall, Ionis’ chief operating officer. “Targeting MAPT [the gene that generates tau protein] represents a unique opportunity to address the unmet need in both rare and more prevalent tauopathies. The first clinical study with IONIS-MAPTRx is in patients with AD. However, in parallel, we also plan to develop IONIS-MAPTRx for patients with FTD, a rare disease population. This strategy has the potential to accelerate the drug’s path to market.”
The start of the trial led to Ionis receiving a $10 million milestone payment from its partner Biogen. The two are collaborating on neurological disorder therapies.
Spinraza (nusinersen) is the partnership’s biggest success so far. It is the first spinal muscular atrophy therapy to receive regulatory approval in the United States and other countries. It is administered similarly to IONIS-MAPTRx.
The partners are also working on a therapy called IONIS-SOD1Rx for amyotrophic lateral sclerosis, or ALS, and other treatments for neurodegenerative diseases.