Buntanetap for Parkinson’s disease
Last updated April 3, 2025, by Lindsey Shapiro, PhD
Fact-checked by Ana de Barros, PhD
What is buntanetap for Parkinson’s disease?
Buntanetap is an investigational oral therapy being evaluated in clinical trials as a possible treatment for Parkinson’s disease.
The therapy, previously known as posiphen or ANVS-401, is being developed by Annovis Bio. A Phase 3 trial testing buntanetap in Parkinson’s disease has been completed, and Annovis indicated plans to meet with U.S. regulators to discuss the regulatory path forward for the experimental treatment.
The company is similarly testing buntanetap for other neurodegenerative diseases, including Alzheimer’s disease and Lewy body dementia.
Therapy snapshot
| Treatment name: | Buntanetap |
| Administration: | Being tested as oral capsules |
| Clinical testing: | Phase 3 trial in Parkinson’s disease complete |
How does buntanetap work in Parkinson’s disease?
A hallmark of Parkinson’s disease is the toxic accumulation in the brain of certain proteins, especially alpha-synuclein, which contributes to nerve cell damage and degeneration.
Buntanetap is a small molecule that works to lower production of neurotoxic proteins by blocking their translation, or the process through which cells “read” a genetic template molecule called messenger RNA (mRNA) to produce a protein.
Translation of neurotoxic proteins is usually inhibited by iron regulatory protein 1 (IRP1), which binds to mRNA and stops cells’ protein-making machinery from being able to access it. However, in states of injury or disease, like Parkinson’s, cellular iron levels rise, which causes IRP1 to release the mRNA and allow neurotoxic protein production. Buntanetap aims to boost IRP1’s binding to the mRNA, thereby increasing its ability to block neurotoxic protein translation.
In doing so, the therapy is expected to help protect nerve cells from the damaging effects of alpha-synuclein, ultimately easing Parkinson’s symptoms and slowing disease progression. Because buntanetap is expected to broadly inhibit neurotoxic protein translation, Annovis also anticipates it will be of benefit for other neurodegenerative diseases where proteins harmfully accumulate.
How will buntanetap be administered in Parkinson’s disease?
In Parkinson’s disease clinical trials, buntanetap has been administered as daily oral capsules at a range of dose levels. In a Phase 3 trial, it was given at a dose of 10 mg or 20 mg, taken once daily.
Buntanetap in Parkinson’s disease clinical trials
The first study to evaluate buntanetap in people with Parkinson’s disease was a Phase 1/2 clinical trial (NCT04524351) involving 54 people with early Parkinson’s and 15 with early Alzheimer’s, all ages 45 and older. Across two study parts, Parkinson’s participants were randomly assigned to receive oral buntanetap at a dose of 5, 10, 20, 40, or 80 mg — or a placebo — once daily for 25 days, or a little under a month.
Results showed that the treatment was well tolerated. Buntanetap was generally associated with improvements in cognitive processing speeds and motor function relative to the placebo. The greatest benefits were observed at daily doses of 10 mg and 20 mg, per Annovis. Buntanetap also tended to be associated with reductions in disease-related biomarkers, including neurotoxic protein accumulation, inflammatory markers, and markers of nerve damage.
Phase 3 trial
A Phase 3 trial (NCT05357989) then enrolled 523 people with early-stage Parkinson’s, ages 40-85. A small proportion of participants (12%) exhibited cognitive impairments at the time of study enrollment. Participants were randomly assigned to receive buntanetap (10 or 20 mg), or a placebo, once daily for six months on top of standard Parkinson’s treatments.
The study’s main goal was to evaluate the changes in scores on Part II of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), which evaluates the effects of motor symptoms on daily living, when off of other Parkinson’s medications.
Results showed that patients who had been diagnosed within the last three years had minimal deficits in MDS-UPDRS Part II, making it difficult to assess treatment efficacy.
But in patients who had been diagnosed with Parkinson’s more than three years prior to study enrollment, buntanetap at its 20 mg dose led to significant improvements in MDS-UPDRS Part II scores relative to the placebo. Total MDS-UPDRS scores, reflective of overall disease severity, as well as scores on MDS-UPDRS Part III (motor symptoms) and Part IV (motor complications), also significantly favored buntanetap in that patient group.
Gains across MDS-UPDRS assessments were particularly notable in participants with postural instability and gait problems, a subgroup known to have faster disease progression.
Study data also showed that buntanetap at either dose was associated with a preservation of cognitive abilities, in contrast to deterioration observed in the placebo group.
Common side effects of buntanetap
Buntanetap is still being evaluated in clinical trials, and its safety profile in people with Parkinson’s disease is not fully established. Annovis reported that in a Phase 3 trial, buntanetap had a strong safety profile, with no serious side effects considered related to the treatment.
In early clinical studies, some side effects that could be related to buntanetap included:
- headache
- skin redness
- muscle spasms and movement problems.
Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
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