Background:
Opportunistic Infections (OIs) caused by pathogenic microorganisms such as
Cryptococcus neoformans, Candida albicans and Aspergillus fumigatus are growing
medical concerns for immuno-compromised patients such as those with AIDS,
diabetes, organ transplant patients, patients on cancer chemotherapy, and several
others. The burden imposed by these infections is staggering, both in terms of
economic loss and human suffering. In sub-Saharan Africa for example, 15-30% of all
patients with AIDS develop cryptococcal disease and cryptococcal meningitis occurs
in 30% of these individuals. If not properly treated, these OIs are often fatal.
Statement of Problem:
1.3 million people in the US are living with HIV, with 20% unaware of their status. With
their immune systems compromised, up to 90% will experience an OI episode. The
medications available for treating OIs are limited because they were not important
prior to the AIDS epidemic. Unfortunately, even the limited numbers are further limited
by resistance development, drug interactions and toxicity. Amphotericin B, the gold
standard for OI treatment produces nephrotoxicity in patients on the drug.
Potential Solution:
Our invention comprises the discovery and in vivo validation of the efficacy of
natural product?derived agents with potent, less toxic and overall better therapeutic
profiles than Amphotericin B. For example, one of the discoveries decreased brain
C. neoformans infections 50% more than Amphotericin B in animal models of the
infection. Because they have different mechanisms of action, these compounds will
be complementary to those currently on the market and might be useful in
treatment?resistant cases especially. Another exciting aspect is that unlike the drugs
on the market, external application of the new compounds would have limited
capacity to cause systemic toxicity.
The Benefits:
? The new drugs are effective against a broad spectrum of opportunistic infections
? They will treat opportunistic infections without nephrotoxicity.
? These drugs should be complementary to the drugs currently available and thus
might be useful in treatment-resistant cases.
Commercialization Status:
Indoloquinolinium salts and their derivatives are currently in the pre-clinical
development stage. This research has been funded by the National Institutes of
Health, NIAID/NCRR. Validation of the observed activities in larger animal models is
planned along with additional pharmacokinetic studies. We seek venture capitalists
and partners or licensees with interest in small molecule drug development in the
Biotechnology and/or Pharmaceutical Industries.
Brochure
