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Primary Amebic Meningoencephalitis (PAM)

Primary amoebic meningoencephalitis (PAM) is a rare infectious disease of the central nervous system caused by the single-celled organism Naegleria fowleri. Relying on advanced technology platforms and professional scientific research talents, our company can provide customized solutions and comprehensive support for PAM therapy development, thereby promoting your scientific research process.

Overview of PAM

PAM is considered an extremely rare disease, with an average of 3.7 cases reported globally each year. Acute amoebic meningoencephalitis is more common in children and adolescents who swim in contaminated ponds or swimming pools. This waterborne disease is characterized by rapid onset and extremely high mortality, with a case fatality rate as high as about 95%. The disease has a short incubation period, and PAM individuals usually develop symptoms within 3-5 days after infection and eventually die due to severe brain edema, leading to respiratory, circulatory, and central system failure.

The pathogenesis of PAM is mainly related to Naegleria fowleri infection. Naegleria fowleri lives in warm freshwater and soil around the world. After Naegleria fowleri invades the nasal mucosa, it enters the brain along the olfactory nerve through the cribriform plate, causing inflammation and hemorrhagic necrosis of the olfactory bulb and brain tissue.

Fig.1 Pathogenesis and therapeutic strategy of PAM.Fig.1 Pathogenesis and therapeutic strategy of PAM. (Güémez, et al., 2021)

Diagnostics Development of PAM

The early symptoms of PAM are similar to bacterial or viral meningitis, making it difficult to diagnose. At present, the diagnostic methods of PAM mainly include laboratory diagnosis and radiological diagnosis.

Laboratory Diagnosis

Laboratory diagnosis involves the examination of cerebrospinal fluid (CSF) samples. The characteristic appearance of Naegleria fowleri, namely a single nucleus and vacuolated cytoplasm, can be observed on cerebrospinal fluid smears or histological H&E-stained slides. In addition, advanced molecular techniques including PCR have been developed to identify Naegleria fowleri DNA present in CSF samples.

Radiological Diagnosis

Radiological imaging, particularly computed tomography (CT) and magnetic resonance imaging (MRI), plays a crucial role in the diagnosis and evaluation of PAM. These imaging techniques can reveal characteristic findings, such as brain edema, hydrocephalus, and necrotic changes in the brain tissue, helping to differentiate PAM from other central nervous system infections.

Therapeutics Development of PAM

  • Targets of PAM Therapy Development
Target Name Description
Naegleria Fowleri Developing drugs that can specifically target and eliminate the Naegleria fowleri from the central nervous system is essential. For example, amphotericin B and miltefosine are antibacterial agents that have shown some efficacy against Naegleria fowleri.
Inflammatory Response Pathways Anti-inflammatory drugs that target specific inflammatory pathways hold the promise of mitigating the damage caused by the immune response. Cyanomethylvinyl ether helps regulate the immune response by regulating the production and activity of pro-inflammatory cytokines, thereby reducing the inflammatory response of PAM.
  • Types of PAM Therapy Development

Immunomodulatory therapy holds promise for managing PAM. Monoclonal antibodies, immune checkpoint inhibitors, and adoptive cell therapies are being explored to enhance the host immune response against Naegleria fowleri. These therapies aim to harness the power of the immune system to specifically target and eliminate the amoeba.

Our Services

As a frontrunner in the field of biological research and CRO services, our company is dedicated to offering holistic solutions for the diagnostics development and therapy research of PAM. Through collaborations with industry experts, we have established an all-encompassing platform for rare diseases to facilitate PAM therapy development.

Platforms of PAM Therapy Development

Recognizing the significance of dependable animal models in PAM disease research, our company is committed to offering animal model development services that facilitate preclinical research and aid in drug discovery endeavors.

Animal Models of PAM

  • Rabbit model of amoeba infection
  • Mouse model of amoeba infection
  • Rat model of amoeba infection

With complete animal species resources, we can meet your diversified preclinical research including drug safety evaluation and pharmacokinetic analysis. If you are interested in our services, please feel free to contact us for more details and quotation information for related services.

References

  • Güémez, Andrea, and Elisa García. "Primary amoebic meningoencephalitis by Naegleria fowleri: pathogenesis and treatments." Biomolecules 11.9 (2021): 1320. 
  • Hall, Ashton D., et al. "Primary amebic meningoencephalitis: a review of Naegleria fowleri and analysis of successfully treated cases." Parasitology Research 123.1 (2024): 84.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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