Snowdon

Therapeutic Area: Infectious Diseases

Parasitic Diseases

The parasites known as Apicomplexans cause some of the most serious and, in some cases, deadly diseases in humans and animals. Notable among these diseases are Malaria, Toxoplasmosis, Cryptosporidiosis, Cyclosporiasis, Babesiosis, and Isosporiasis in humans and Neosporosis, Coccidiosis, Eimeria and Theileria in domestic animals.

Cryptosporidium, Cyclosporiasis, and Toxoplasmosis are listed as Category B biodefense pathogens by the NIH-NIAID.

The medical, social, and economic impact of these pathogens on a global scale is enormous. Despite major efforts to control these parasites, progress to date has been inadequate. Many of these parasites are resistant to common disinfectants such as bleach and iodine solutions. The development of parasitic resistance to existing drugs and insecticides, and the lack of efficacious vaccines against any of these diseases, has made the discovery and development of new drugs a matter of extreme urgency.

To address this significant medical and public health issue, Snowdon has discovered a family of highly potent small-molecule compounds that kill the parasite by inhibiting its vulnerable invasive machinery. Our inhibitor molecules were computationally designed to block a key protein-protein interaction that is indispensable for these parasites to move and to invade the host’s cells. This particular interaction is unique to these parasites, consequently our inhibitor molecules should be safe for humans and other mammals. Furthermore, the ability of these parasites to acquire resistance to our inhibitor molecules is highly unlikely.

Malaria, caused by the parasite known as Plasmodium, is perhaps the world’s most devastating human infectious disease. There are over 600 million people in the world with this disease, and each year about 2 million people (mostly children) die from its effects. There are four parasitic species that cause human malaria; namely Plasmodium (P.) falciparum, P. vivax, P. ovale, and P. malariae. While P. vivax and P. falciparum are the most widely distributed species, P. falciparum alone is responsible for the most severe clinical cases and 95% of the 2 million worldwide deaths resulting annually from malarial infection. The economic and social impact of malaria is alarming, and traditional chemotherapy agents are failing due to growing parasitic resistance. Snowdon’s inhibitor molecules have shown an extraordinary ability to kill the parasite without toxicity in mice.

Toxoplasmosis is the leading cause of severe congenital neurological defects in humans, and is a frequent cause of still births and spontaneous abortions. Toxoplasmosis is found throughout the world, and nearly one-third of all adults in the USA and Europe are infected with this parasite. In pregnant women, Toxoplasmosis can cause severe birth defects (brain and eye damage) or miscarriage of the fetus. It is estimated that approximately 3,000 children in the USA are born infected with Toxoplasmosis every year. Although the majority of infected infants show no symptoms of Toxoplasmosis at birth, many are likely to develop signs of infection later in life.

Toxoplasmosis is also a very serious opportunistic infection that can cause blindness or life-threatening meningitis in immunocompromised individuals such as HIV/AIDS patients, in people receiving cancer chemotherapy, and in organ transplant recipients. Although infected cats are well recognized as a source of Toxoplasmosis, most infections in the USA and Europe among adults are probably acquired from undercooked meat. Therapeutic agents have been sorely lacking, and maintenance therapy has become necessary. In contrast, Snowdon’s therapeutic agents target the underlying cause – not just the symptoms – of this dread parasitic disease.

Cryptosporidiosis, commonly known as “Crypto”, is now recognized as one of the most common causes of waterborne disease within humans in the USA and worldwide. It causes chronic diarrhea that is especially serious and sometimes fatal in immunocompromised individuals. Recent evidence suggests that Crypto is responsible for 250-500 million cases of diarrhea annually. Crypto-associated diarrhea is also a widespread problem in the cattle industry.

Over 10 serious outbreaks of Crypto were reported in the USA during the past decade. A massive outbreak occurred in 1993 when over 400,000 people in Milwaukee became seriously infected and several died. Crypto can occur by drinking contaminated water or eating contaminated food. Several outbreaks of Crypto have been traced to swallowing contaminated water while swimming. Crypto is not killed by the amount of chlorine normally used in swimming pools and water parks. The parasite can remain alive in salt water for several days, so swimming in polluted ocean water may also be unsafe. Moreover, the parasite can survive outside the body for long periods of time and is highly resistant to disinfectants such as chlorine bleach and iodine. Currently there is no known effective therapy for human cryptosporidiosis.

Cyclosporiasis, which causes prolonged and recurring bouts of diarrhea and other gastrointestinal problems in humans, is especially severe and sometimes life threatening in immunocompromised individuals such as HIV/AIDS patients. Although therapeutic treatments currently exist, many of them are contraindicated for pregnant women, the elderly, and in people with hepatic and renal impairment. Many existing treatments, such as sulfa drugs, can cause adverse side effects which limit their utility. Snowdon’s molecules work by inhibiting an essential mechanism unique to these parasites, thereby greatly reducing the likelihood for adverse drug effects.

Babesiosis is a tick-borne illness that infects a wide variety of wild and domestic animals throughout the world, including humans. Human infections in the U.S. are prevalent along the northeastern costal region, giving rise to the name ‘Nantucket fever’. Infections in Europe are less frequent but more serious. Most of these infections have been associated with individuals who have frequent contact with cattle. Babesiosis is particularly severe, and can be life-threatening, in splenectomized, elderly, and immunocompromised individuals. Approximately 25% of patients with Babesiosis are co-infected with Lyme disease. There are no drugs recognized as effective against Babesiosis.

Isosporiasis, caused by the Isospora belli parasite, infects both humans and animals. Infection causes acute debilitating diarrhea which can last for weeks. Outbreaks are more frequent, and more severe, in institutionalized settings in the USA. In immunocompromised patients, and in infants and children, the diarrhea can be severe and sometimes life-threatening.

Neosporosis infects a wide variety of mammals including dogs, cats, cattle, horses, rodents, sheep, and deer. It is a major cause of abortions and stillbirth in cattle worldwide. The economic impact of Neosporosis infection of cattle is staggering. Incredibly, no drugs or vaccines have been shown effective to reduce or prevent infection.

Coccidiosis is a generic name given to a host of highly contagious animal-specific intestinal diseases caused by the coccidia parasite. Susceptible animals range from household pets like cats and dogs, to entire herds of cattle, and even large flocks of birds and poultry. Infected animals generally experience diarrhea, vomiting, and dehydration which can be fatal.

Eimeria and Theileria mainly infect domestic animals and livestock (e.g., cattle, sheep, pig, chicken), causing massive economic damage along with loss of life and livelihood.

Therapeutic Areas: Cancer | Acute and Chronic Pain | Infectious Diseases | Neurological Diseases