Delaying early-stage ALS with microbiota transplants

summary: Fecal microbiota transplantation from healthy individuals can help slow the progression of early ALS by altering the patient’s microbiota and intervening in the inflammatory process.

sauce: European Society for Clinical Microbiology and Infectious Diseases

In a randomized clinical trial, fecal microbiota transplantation (FMT) from healthy donors to adults with early-stage amyotrophic lateral sclerosis (ALS – one of the most common forms of motor neuron disease) We are investigating whether it can modulate the immune response during the characteristic inflammatory response. The aim is to investigate the relationship between specific gut bacteria and their effects on immune system cells.

Preliminary findings by Dr. Alessandra Guarnaccia of Columbus-Gemelli University Hospital IRCCS (Rome, Italy) and colleagues will be presented at this year’s European Conference on Clinical Microbiology and Infectious Diseases (ECCMID) in Copenhagen, Denmark (15-18 April). day) will be announced.

ALS is a devastating condition in which motor neurons in the spinal cord and brain degenerate, causing progressive paralysis, worsening disability, and eventual death within an average of 2-5 years.

ALS is the most common form of motor neuron disease, with an average incidence of 2.8 per 100,000 in Europe and 1.8 per 100,000 in North America.

About 5-10% of people with ALS have various genetic causes that can be passed on in families, but 90% are known as “sporadic” disease because the cause is unknown. I have a thing This makes it difficult to find one treatment that works for all her ALS patients.

Recent findings suggest that oxidative stress (imbalance between free radical chemicals and antioxidants in the body), neuronal damage or death (exotoxicity), and activation of pro-inflammatory pathways are key to this disease. suggesting that it is a trigger factor.

Given the role of regulatory T cells (Treg) in regulating or suppressing the immune system, increasing or activating cell populations in ALS patients is thought to have therapeutic benefits.

It has long been known that alterations in the composition of the gut microbiota may be associated with many neurological diseases through the ‘gut-brain axis’. Indeed, specific gut microbiota populations (proteobacteria) crosstalk with the immune system and promote activation of pro-inflammatory pathways following loss of Treg numbers and suppressive function.

Moreover, previous mouse models have shown severe impairment of the gut microbial population during the early stages of ALS, pointing to a possible role of the gut microbiota in the development of ALS.

FMT is already used in clinical practice to restore the gut microbiota balance and modulate recurrent gut and systemic immunity. Clostridioides difficile Infection.

The trial randomized 42 ALS patients (ages 18-70) who had symptoms within 18 months to receive either FMT (28 patients) or placebo (14 controls). . At the beginning of the study and 6 months later, researchers inject gut microbes from healthy donors into patients in the intervention group, while patients in the control group do not.

On the day of each procedure, researchers will collect stool, saliva and blood samples to assess how the transplant affected gut microbiota, immune cells and inflammatory status. This may shed light on the early processes that can lead to the degenerative ALS course.

Each patient will also undergo three endoscopies (at the start of the study and at months 6 and 12) to perform intestinal biopsies.

The primary outcome was a significant change in Treg numbers from study entry to 6 months between FMT-treated patients and controls.

FMT has been shown to be a safe treatment for these patients, and no adverse events have been reported to date.

Preliminary results outlining the gut microbiota profile of six patients at the start of the study showed the relative abundance of Proteobacteria, a large group of microbes with surface proteins that can readily activate the immune system. was found to be much higher (15% on average). This activation alerts the body to disease and causes the release of molecules that cause inflammation.

“There is a huge unmet need for the treatment of ALS and our research is opening up an entirely new pathology that can be addressed,” says Dr. Guarnaccia. “It is hoped that FMT will increase the number of Tregs, switch the immune system surrounding motor neurons to an anti-inflammatory, neuroprotective state, and slow the progression of ALS.”

Professor Luca Masucci, author of the Catholic University of the Sacred Heart in Rome, Italy, adds: In 2024, we hope to be able to analyze all data from this trial. ”

ALS can affect anyone regardless of race, ethnicity, or socioeconomic background. In general, symptoms often develop between the ages of 40 and 70, with an average age of 55 at diagnosis.

Many prominent British sportsmen, including rugby league’s Rob Barrow, rugby union’s Dodi Weir and footballer Stephen Darby, have shared their experiences with motor neuron disease in recent years.

Professor Stephen Hawking, who also had the disease, lived 55 years from diagnosis to his death in 2018 at the age of 76.

About this ALS Research News

author: Simone Bruderli
sauce: European Society for Clinical Microbiology and Infectious Diseases
contact: Simone Brüderli – European Society for Clinical Microbiology and Infectious Diseases
image: image is public domain

Original research: Findings will be presented at ECCMID 2023