Alpha-synuclein is a protein naturally found mainly in brain cells (neurons) where it regulates the release of neurotransmitters such as dopamine, allowing communication between the neurons.

In Parkinson's disease, this protein sticks together into toxic clumps that cause nerve cell death and leads to patients suffering from symptoms such as tremors, difficulties moving and muscle stiffness. Whilst there are treatments available to relieve symptoms, there is currently no cure.

Normally, alpha-synuclein's natural or "native state" is like a flexible strand, but when active it shapes itself into a helix, which is critical for its function in binding and transporting parcels of dopamine.

The team engineered a peptide fragment that locks alpha-synuclein into its healthy shape, blocking its conversion into the toxic clumps that cause nerve cell death.

Laboratory tests showed the peptide is stable, penetrates brain-like cells, and restores movement while reducing protein deposits in a worm model of Parkinson's.

This breakthrough, published in the journal JACS Au, demonstrates the potential of rational peptide design to transform large, unstable proteins into compact drug-like molecules.

The findings mark a significant step towards developing new peptide-based treatments for currently untreatable neurodegenerative conditions. Professor Jody Mason, from the Department of Life Sciences at the University of Bath, said: "Our work shows that it is possible to rationally design small peptides that not only prevent harmful protein aggregation but also function inside living systems.

"This opens an exciting path towards new therapies for Parkinson's and related diseases, where treatment options remain extremely limited."

Dr Julia Dudley, Head of Research at Alzheimer's Research UK, which funded the research, said:

"Dementia isn't an inevitable part of ageing; it's caused by diseases like Alzheimer's. To make progress towards a cure for all forms of dementia, we need research focused on developing a broad range of treatments that can slow, stop and ultimately reverse these diseases.

"Although this is early research in an animal model, it's exciting to see that this new molecule can prevent the build-up of misfolded alpha-synuclein.

"By stabilizing alpha-synuclein in its healthy form, this could open the door to a new class of treatments that could slow progression in diseases like Parkinson's and dementia with Lewy bodies. We look forward to seeing this research taken to the next stage, potentially exploring how it would work in people.

"We're delighted to see such promising advances from Alzheimer's Research UK funded work opening up new avenues for treatments of the future, and the potential to change the lives of those affected by neurodegenerative diseases."

Further research is needed, but the team hopes that continued progress will enable these and similar molecules to advance towards clinical testing in the coming years.

• Results from the FigHTN Phase 2 clinical trial showed baxdrostat, a new medication that inhibits the production of the hormone aldosterone, lowered systolic blood pressure by about 5% when added to the existing medications taken by people with chronic kidney disease and who also have uncontrolled high blood pressure.
• The analysis also found that baxdrostat lowered the loss of albumin in the urine, which is a marker of kidney and cardiovascular risk, by 55% compared to placebo, suggesting that this medication may help delay the progression of kidney disease .
• These findings suggest the potential for baxdrostat to improve longer-term health outcomes like kidney and cardiovascular conditions and reduce the need for higher-cost care for people with uncontrolled high blood pressure and chronic kidney disease.

Adding the novel medication baxdrostat to standard care may help manage high blood pressure and delay the progression of kidney disease in people with chronic kidney disease and uncontrolled high blood pressure , according to preliminary research presented at the American Heart Association's Hypertension Scientific Sessions 2025. This study was simultaneously published in the Journal of the American Society of Nephrology.

Chronic kidney disease and high blood pressure are closely linked and, when not managed appropriately, can lead to serious outcomes such as heart attack, stroke, heart failure and progression to kidney failure. Aldosterone, a hormone produced by the adrenal glands, can play a role in both high blood pressure and chronic kidney disease. Aldosterone causes sodium to be retained, which increases water retention and blood pressure. Over time, an excess of the hormone can lead to stiffening and thickening of blood vessels, which can contribute to heart damage and cause scarring in the kidneys, thereby playing a role in both high blood pressure and chronic kidney disease.

"These findings are encouraging for people living with chronic kidney disease and high blood pressure, two conditions that often go hand-in-hand and create a dangerous cycle," said lead study author Jamie P. Dwyer, M.D., a professor of medicine in the division of nephrology and hypertension at University of Utah Health in Salt Lake City. "High blood pressure can worsen kidney function and declining kidney function can further elevate blood pressure, and these outcomes can be life-altering for patients."

The study was designed to find whether adding baxdrostat to standard care is safe and could help lower blood pressure in people who have both chronic kidney disease (serious enough that they are likely to develop kidney failure or require a transplant during their lifetime) and uncontrolled high blood pressure. Their blood pressure has remained high despite already taking either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), two medications that work on a group of hormones that act together to regulate blood pressure.

At the beginning of the study, participants had an average systolic (top number) blood pressure of 151 mm Hg despite treatment and evidence of kidney disease on laboratory testing. When the protein albumin was measured in the urine, the average level for participants was 714 mg/gm of creatinine; levels of 30 or higher may be a sign of chronic kidney disease. When a blood sample was used to measure the estimated glomerular filtration rate (eGFR, a key indicator of kidney function), the average level was 44mL/min/1.73. Levels that are persistently less than 60 suggest chronic kidney disease.

Of 195 initial study participants, 192 were randomized to begin treatment with low-dose (0.5 mg-1 mg) or high-dose baxdrostat (2 mg-4 mg) or a placebo in addition to standard care. Three people finished the study early due to adverse events, their own decision to leave the study or for other reasons.

After 26 weeks:

• The average systolic blood pressure had fallen 8.1 mm Hg more in participants receiving either dose of baxdrostat than in those receiving the placebo, a reduction of about 5%.
• High potassium levels in the blood, a known side effect of medications that block the renin-angiotensin-aldosterone system, occurred in 41% of participants on baxdrostat and 5% of those on placebo. Most cases were mild to moderate.
• There were no deaths or unanticipated adverse events during the trial, however, 9% of participants taking baxdrostat and 3% of those in the placebo group experienced a serious adverse event.

In an exploratory analysis, the researchers looked at the amount of albumin lost in the urine, a type of protein that when found in the urine in high amounts is a predictor of cardiovascular and kidney disease. They found the urine albumin level was 55% lower in those taking baxdrostat than in those taking a placebo, comparable to the reduction seen with medications that delay the progression of kidney disease.

"The reduction in urine albumin gives us hope that baxdrostat may also help delay kidney damage. This potential is now being tested in two large Phase 3 trials to determine if baxdrostat delays the progression of kidney disease," said Dwyer.

"These new findings are reassuring that this new class of antihypertensive medications are likely to have both kidney- and cardio-protective benefits and to be safe and effective for broad patient populations," said Jordana B. Cohen, M.D., M.S.C.E., immediate past chair of the American Heart Association's Hypertension and Kidney Cardiovascular Science Committee. "Patients with chronic kidney disease were historically often excluded from drug studies. It is particularly reassuring to know that patients with chronic kidney disease, who have very high rates of hypertension and elevated renin-angiotensin aldosterone activity, were represented in their own study, tolerated the medication well, and had both blood pressure and albuminuric benefits. This medication class could be a game changer in the management of hypertension in this patient group." Cohen, who was not involved in this study, is deputy director and associate professor of medicine and epidemiology in the Perelman School of Medicine at the University of Pennsylvania.

Study details, background and design:

• The study included 195 people with an average age of 66 years. Of the participants, 32% were women, 40% were non-Hispanic white and 80% had Type 2 diabetes. The study was conducted at 71 sites in the United States. Three participants were not randomized or included in the final analysis.
• All participants had uncontrolled high blood pressure (systolic blood pressure of 140 mm Hg or higher, or 130 mm Hg or higher for people with Type 2 diabetes ) despite taking the maximum tolerated dose of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker among their medications, with average systolic blood pressure of 151.2 mm Hg at the start of the study.
• All participants also had chronic kidney disease but were not in kidney failure (eGFR of 25-75 mL/min/1.73, average eGFR of 44 mL/min/1.73 at the start of the study; and urine albumin-creatinine ratio of 100 mg/g or higher, average of 713.8 at the start of the study).
• The 192 participants were randomized to one of the three treatment groups: low-dose baxdrostat (0.5 mg/day, increasing to 1 mg/day after two weeks); high-dose baxdrostat (2 mg/day, increasing to 4 mg/day after two weeks); or a placebo.
• After 26 weeks, blood pressure and kidney function tests were repeated, and the primary analysis compared changes in systolic blood pressure among the three groups. Adverse events were also reported for each of the three treatment groups.
• Baxdrostat is in a class of medications that inhibit the production of aldosterone and are being tested for their ability to treat conditions such as high blood pressure, chronic kidney disease and heart failure. Baxdrostat is not approved for any use by the U.S. Food and Drug Administration.

Co-authors and their disclosures and funding sources are listed in the abstract. The study was funded by AstraZeneca, developer of baxdrostat.

Note: The study featured in this news release is a research abstract. Abstracts presented at the American Heart Association's scientific meetings are not peer-reviewed, and the findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal.