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Cryptococcosis

Due to the epidemiological concern and high morbidity and mortality associated with fungemia, Cryptococcosis is an infectious disease caused by a fungus that has gained significant attention from researchers. Our organization is fully prepared to meet your development needs for drugs and therapies related to Cryptococcosis.

Introduction to Cryptococcosis

This particular disease is caused by a fungal infection, primarily Cryptococcus neoformans or entering through the nasal cavity along with other respiratory pathogens like Cryptococcus gattii which may infect the lungs and central nervous system. This disease is one of the major health risks for immunocompromised persons, particularly cases of HIV/AIDS. Out of more than 65 million people infected with HIV worldwide, there are approximately 152,000 suffering from cryptococcal meningitis annually. Out of which, roughly 112,000 deaths occur, primarily in the sub-Saharan region of Africa due to undetected and untreated HIV/AIDS and lack of antiretroviral therapy.

Molecular Diagnosis Development of Cryptococcosis

Nucleic Acid Sequence-Based Amplification (NASBA): NASBA represents one of the more advanced molecular diagnostic techniques for the identification and detection of Cryptococcus infection. With NASBA technology, the time required to accomplish amplification is significantly reduced. NASBA has shown higher sensitivity than colloidal gold methods regarding the detection of Cryptococcus RNA in clinical materials, particularly blood samples.

Antifungal Agents and Their Cellular Targets

  • Polyenes: This class of drugs, like amphotericin B, targets and binds to ergosterol in the fungal cell membrane. This contributes to the disruption of membrane integrity leading to the outflow of cellular constituents and ultimately cell death.
  • Azoles: These drugs, such as fluconazole, inhibit fungal growth by disrupting the synthesis of ergosterol and compromising the structural integrity of the fungal cell membrane through the inhibition of the enzyme lanosterol 14α-demethylase (Erg11).
  • Echinocandins tend to target and inhibit Fks1, a β-1,3-glucan synthase which may result in the disruption of the fungal cell wall.
  • Pyrimidine Analogues: Such as flucytosine acts by disrupting the synthesis of DNA and RNA.
Mechanisms driving resistance to existing antifungal treatments in Cryptococcus species.

Fig. 1 Mechanisms governing resistance to current antifungal agents in Cryptococcus spp. (Iyer, K.R., et al., 2021)

Vaccine Development of Cryptococcosis

Type Vaccine Background Mechanism Development Stage
Whole cell vaccines (live-attenuated or killed cells) H99γ Live Cryptococcus neoformans strain expressing human IFN-γ T cell response Preclinical
Cda123 Live or heat-killed C.neoformans strain lacking Chitin deacetylase activity T cell response Preclinical
Znf2OE C.neoformans strain overexpressing transcription factor Znf2 T cell response Preclinical
Recombinant vaccines or subunit vaccines GXM-TT C.neoformans GXM conjugated with tetanus toxoid Antibody response Preclinical
Glucan particles Glucan particles packaged with C.neoformans alkaline extracts Antibody and Tcell responses Preclinical
Antibody-based vaccines GXM antibody 18B7 C.neoformans GXM monoclonal antibody Therapeutic antibody Phase1
P13 A peptide mimic of C.neoformans GXM Antibody response Preclinical
β-Glucan antibody β-Glucan monoclonal antibody Therapeutic antibody Preclinical

Our Services

Our company takes a partnership approach, working alongside clients to develop innovative and effective strategies for the therapeutic of Cryptococcosis. We assist at every stage of the development to guarantee optimal and effective results.

Platforms of Cryptococcosis Therapy Development

Animal Models of Cryptococcosis

We know how to construct and use animal models that closely reproduce the salient features of Cryptococcosis and its therapeutic responses. Such models allow for an accurate assessment of the safety and effectiveness of new medication candidates.

Non-Genetically Engineering Models
We provide an array of models designed to meet specific research requirements for Cryptococcosis. These models allow researchers to replicate and study the intricate biological processes associated with the disease.
Optional Models
  • Cryptococcus -Induced Cryptococcosis Model
Genetically Engineered Models
Our expertise in genetic engineering techniques, enables us to create precise and reliable models that replicate the genetic alterations seen in Cryptococcosis.
Optional Models
  • IFN-γ Knockout Mouse Model
  • CAP10 Mutant Model
Optional Species Mice, Rats, Non-human primates, Others

In addition, we offer a range of comprehensive animal model services that concentrate on specific signaling pathways and molecular targets.

If you are interested in our services, please contact us as soon as possible for more information.

References

  • Iyer, K.R., et al., "Treatment strategies for cryptococcal infection: challenges, advances and future outlook." Nat Rev Microbiol, (2021). 19(7): p. 454-466.
  • Wang, Y., et al., "Application and evaluation of nucleic acid sequence-based amplification, PCR and cryptococcal antigen test for diagnosis of cryptococcosis." BMC Infect Dis, (2021). 21(1): p. 1020.

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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