Summary: A diagnostic test has revealed that Ambroxol, a typical cough medicine in Europe, may help slow mental decline in people with Parkinson’s condition memory. The 12-month investigation found that the drug stabilized medical signs, protected against mind damage, and even improved consciousness in physically at-risk participants.
Ambroxol boosts an enzyme called GCase, which is often lacking in Parkinson’s people, contributing to mental cell damage. While hardly yet approved for use in North America, the drug’s health status and first rewards make it a compelling candidate for further investigation.
Important Information:
- Stabilized Symptoms: Ambroxol halted clinical reduction seen in the sham party.
- Biological Benefit: Thinking improved in those with GBA1 protein varieties.
- Brain Protection: GFAP, a symbol of head injury, remained steady on Ambroxol.
Origin: Lawson Research Institute
Dementia poses a major health problem with no healthy, affordable therapies to slow its growth.
Researchers at Lawson Research Institute ( Lawson ), the research arm of St. Joseph’s Health Care London, are investigating whether Ambroxol – a wheeze treatments used properly for years in Europe – may slow dementia in individuals with Parkinson’s condition.
Published now in the prestigious JAMA Neurology, this 12-month clinical trial involving 55 participants with Parkinson’s disease dementia ( PDD ) monitored memory, psychiatric symptoms and GFAP, a blood marker linked to brain damage.
Parkinson’s condition memory causes memory loss, confusion, illusions and mood changes. About half of those diagnosed with Parkinson’s develop memory within 10 times, deeply affecting individuals, communities and the health care system.
Led by Cognitive Neurologist Dr. Stephen Pasternak, the investigation gave one party regular Ambroxol while the other party received a placebo.
“Our goal was to change the course of Parkinson’s dementia, ” says Pasternak. “This first trial offers hope and provides a solid base for larger research. ”
Key results from the scientific trial include:
• Ambroxol was healthy, well-tolerated and reached medical levels in the mind
• Psychiatric symptoms worsened in the sham party but remained firm in those taking Ambroxol.
• Individuals with high-risk GBA1 gene variations showed improved mental performance on Ambroxol
• A marker of brain cell damage ( GFAP ) increased in the placebo group but stayed stable with Ambroxol, suggesting potential brain protection.
Although Ambroxol is approved in Europe for treating breathing problems and has a long-standing health history – including use at higher dosages and during childbirth – it is not approved for any use in Canada or the U. S.
“Current treatment for Parkinson’s disease and memory address symptoms but do not prevent the actual condition, ” explains Pasternak.
“These results suggest Ambroxol may shield mental function, especially in those physically at risk. It offers a promising new care street where few now exist. ”
Ambroxol supports a key enzyme called glucocerebrosidase ( GCase ), which is produced by the GBA1 gene. In persons with Parkinson’s condition, GCase rates are usually lower. When this enzyme does n’t work correctly, waste builds up in brain cells, leading to damage.
Pasternak learned about Ambroxol during a fellowship at The Hospital for Sick Children ( SickKids ) in Toronto, where it was identified as a treatment for Gaucher disease – a rare genetic disorder in children caused by a deficiency of GCase.
He is presently applying that study to investigate whether boosting GCase with Ambroxol may help protect the head in Parkinson’s-related illnesses.
“This research is vital because Parkinson’s memory profoundly affects patients and families, ” says Pasternak. “If a substance like Ambroxol you help, it may offer real hope and enhance lives. ”
Funded by the Weston Foundation, this review is an important step toward developing innovative solutions for Parkinson’s illness and other mental disorders, including memory with Lewy body. Pasternak and his team plan to start a follow-up medical test focused exclusively on thinking later this year.
About this neuropharmacology and Parkinson’s condition analysis reports
Author: Debora Flaherty
Source: Lawson Research Institute
Contact: Debora Flaherty – Lawson Research Institute
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Ambroxol as a Treatment for Parkinson Disease Dementia A Randomized Clinical Trial” by Stephen Pasternak et al. JAMA Neurology
Abstract
Ambroxol as a Treatment for Parkinson Disease Dementia A Randomized Clinical Trial
Importance
Carrying a variation in the gene for β-glucocerebrosidase is a major risk factor for Parkinson disease dementia ( PDD), and raising β-glucocerebrosidase levels lowers α-synuclein in cell and animals. Ambroxol is a chaperone for β-glucocerebrosidase, which increases the levels of β-glucocerebrosidase.
Objective
To examine the safety and tolerability of ambroxol in PDD, test the efficacy of ambroxol in improving or slowing the progression of cognitive deficits, and acquire pharmacological data.
Design, Setting, and Participants
This was a 52-week, phase 2, double-blind, placebo-controlled, randomized clinical trial conducted from February 2015 to June 2023. The study took place at a single center and was referral based. Included were patients with PDD who were older than 50 years, had Parkinson disease for at least 1 year before cognitive impairment, had mild to moderate dementia, were taking stable medications, and had a study partner.
Interventions
Ambroxol low dose ( 525 mg per day ), high dose ( 1050 mg per day ), or placebo.
Main Outcomes and Measures
Safety and tolerability outcomes were adverse events. Primary efficacy outcomes were the Alzheimer Disease Assessment Scale–cognitive subscale, version 13 ( ADAS-Cog-13 ) and Clinician’s Global Impression of Change ( CGIC ).
Results
A total of 75 patients were screened, and 55 were randomized. Thirty-one individuals received ambroxol, with 8 patients ( mean [SD] age, 78. 8 [3. 4] years, all male ) in the low-dose group and 22 patients ( mean [SD] age, 70. 7 [7. 6]; 19 male [86. 4 % ] ) in the high-dose group. One patient was excluded from the high-dose group due to a diagnosis of progressive supranuclear palsy.
A total of 24 patients ( mean [SD] age, 72. 7 [6. 3] years; 19 male [79. 2 % ] ) were included in the placebo group. Participants receiving ambroxol ( 23 of 193 adverse events [12 % ] ) showed more gastrointestinal adverse events than those receiving placebo ( 9 of 172 adverse events [5 % ] ). Statistical analyses compared ambroxol high dose vs placebo.
There was no evidence to suggest differences between groups on primary or secondary outcomes. Mean ( SD ) ambroxol high-dose concentrations were 7. 48μM (3. 17μM; 95 % CI, 6. 08-8. 87μM ) in plasma and 0. 73μM ( 0. 07μM; 95 % CI, 0. 64-0. 81μM ) in cerebrospinal fluid at the end of titration.
Mean ( SD ) β-glucocerebrosidase levels were higher at week 26 (ambroxol, 12. 45 [1. 97] nmol/h/mg; 91 % CI, 11. 54-13. 36 nmol/h/mg ); placebo, 8. 50 [1. 96] nmol/h/mg; 91 % CI, 7. 65-9. 34 nmol/h/mg; P =. 05 ) in the ambroxol group compared with placebo.
Conclusions and Relevance
Results of this randomized clinical trial reveal that ambroxol was safe, well-tolerated, and demonstrated target engagement. However, the effect of ambroxol on cognition was not confirmed.
Trial Registration
ClinicalTrials. gov Identifier : NCT02914366
