In February 2022, Chinese Journal of New Drugs and Clinical Remedies published a single-case study by Hu Xiuxiu, Zhan Zhen, et al. from Nanjing Brain Hospital Affiliated to Nanjing Medical University, introducing a case of behavioral variant frontotemporal dementia that was treated with sodium oligomannate in combination with memantine.

Frontotemporal dementia (FTD) refers to a group of dementia syndromes associated with frontotemporal lobar degeneration (FTLD), with the pathogenesis still remaining unclear. Its pathological feature is progressive frontotemporal atrophy that’s also selective, and no drug has ever been approved for treating FTD so far.

The pharmacological treatment of FTLD mainly focuses on the symptomatic treatment of behavioral, motor and cognitive impairments. Studies have confirmed that central and peripheral inflammation is involved in the pathogenesis of FTD, and targeting neuroinflammation may be one of the treatment directions.

At present, there are few drugs available in the market that target neuroinflammation. Sodium oligomannate (marketed as “GV-971”), China’s novel drug for treating Alzheimer's disease (AD) launched at the end of 2019, regulates peripheral and central inflammatory responses by targeting the gut-brain axis to improve cognitive function. For the first time, the case study reports a patient with probable behavioral variant FTD (bvFTD) that was treated with sodium oligomannate in combination with memantine, which provides a reference for the clinical treatment of FTD.

CASE REPORT

With an onset age of less than 65 years old, the patient had psychological abnormalities as the main symptoms, and exhibited apathy, decreased empathy, behavioral disinhibition, obsessive-compulsive or stereotypic behaviors, decreased hobbies and interests, and changes in eating habits in the early stage. However, the patient’s visuospatial functions were retained. Later, the overall cognitive function declined gradually, and the disease progressed rapidly – the neuropsychological test result was “severe dementia”, and head MRI showed frontotemporal atrophy; 18F-FDG-PET-CT imaging showed lower perfusion and lower metabolism of the frontal lobe/anterior temporal lobe; and PIB-PET-CT imaging showed retention of radioactivity in the bilateral parietal, temporal and occipital cortex. Considering indications such as PIB positivity, the patient met the clinical diagnostic criteria of probable bvFTD.

At the time of hospital admission, the patient had a MMSE (Mini-Mental State Examination) score of 1 and a MoCA (Montreal Cognitive Assessment) score of 0, and was classified as “severe dementia”. The patient’s activities of daily living were severely impaired, including bladder and bowel incontinence. Since donepezil combined with memantine was unable to control disease progression, the patient’s treatment plan was modified to memantine combined with sodium oligomannate after hospital admission. After two weeks of treatment, the patient's cognitive function, psychological symptoms, and stereotypic behaviors were improved, indicating that memantine combined with sodium oligomannate had better curative effects on the patient than memantine combined with donepezil.

After more than one year of follow-up, the overall cognitive function of the patient was not significantly decreased, along with improved activities of daily living and affective responses. Given the patient’s long-lasting course of treatment, it is expected that through long-term follow-up observations, the degree of improvement in clinical symptoms and neuropsychological scales will be further evaluated.

DISCUSSION

The etiology and pathogenesis of FTD still remain unclear. In terms of pathogenesis, neuroinflammation is involved in the pathological process of FTD, including cortical inflammation, microglia activation, astrogliosis, and overexpression of peripheral inflammation-related proteins. Gut microbiota dysbiosis is involved in the process of psychiatric disorders such as mood disorders and autism, and regulating gut microbiota dysbiosis may be a potential therapeutic target for treating such diseases.

Basic research shows that sodium oligomannate can reduce neuroinflammation by targeting the gut-brain axis, reducing the infiltration of Th1 cells into the brain, and reducing the activation of microglia. After more than one year of treatment with sodium oligomannate, the patient's cognitive function and activities of daily living were all improved to a certain extent, the mechanism of action of which may also be related to the reduction of neuroinflammation in the brain.

In conclusion, the bvFTD patient’s psychological symptoms, activities of daily living, and emotional reactions were all improved after treatment with sodium oligomannate, suggesting that sodium oligomannate can be used for treating patients with bvFTD, although further clinical trials are still needed to verify the efficacy.

Link：http://qikan.cqvip.com/Qikan/Article/Detail?id=7106781675