THE CENTER FOR APPLIED TOXINOLOGY (CAT), A PLATFORM FOR DRUG DISCOVERY IN BRAZIL (PART I)

ANTONIO C. M. CAMARGO(1)

(1)CAT/CEPID–Fapesp at the Instituto Butantan

The Center for Applied Toxinology (CAT) is a multi-institutional research organization based at the Butantan Institute in São Paulo (Brazil), dedicated to the study of snake toxins and other poisonous organisms. CAT is one of 10 Centers for Research, Innovation and Dissemination (CEPID) (Portuguese: Centro de Pesquisa, Inovação e Difusão) created by a pioneering program of the Research Support Foundation of the State of São Paulo (FAPESP). The program was established to stimulate research, disseminate knowledge, and foster interaction between science and industry.

Nature’s Blockbusters

During evolution, poisonous animals became specialized in affecting vital functions of their prey. For instance, venom from Bothrops or Crotalus snakes harm, respectively, the cardiovascular system and the central nervous tissue of their prey. However, snake venoms never limit their action to a single target molecule in order to affect an important physiological function of their prey. Both Bothrops and Crotalus snakes  produce a number of toxins (mainly enzymes and peptides) that imbalance the physiological levels of hormones by disturbing the activity of critical enzymes, receptors or ion channels, thus disarranging the whole cardiovascular or nervous systems of their victims. Moreover, a toxin is frequently associated with a number of highly homologous molecules displaying distinct specificity toward the same target.

Venom glands can be seen as the R&D department of a natural pharmaceutical laboratory that helps the survival of species by mutating and selecting the most appropriate toxins to ensure that sufficient damage is caused to the prey’s physiological system.

Due to its high target-specificity, venom toxins have been used increasingly as pharmacological tools and prototypes for drug development. While pharmaceutical companies spend millions of dollars searching for pharmacological compounds through extensive screening of chemical libraries, venomous animals, along millions of years, have designed their own blockbuster drugs with the help of natural selection only.

THE CENTER FOR APPLIED TOXINOLOGY (CAT), A PLATFORM FOR DRUG DISCOVERY IN BRAZIL (PART II)

ANTONIO C. M. CAMARGO(1)

(1)CAT/CEPID–Fapesp at the Instituto Butantan

Nature’s Blockbusters (Cont…)

In general, toxins form the main compounds found in venoms, and secretions from a variety of animals, plants, and microbial sources. Toxins can be used for defensive purposes by damage of the cardiovascular or the nervous systems, causing a number of effects such as, blood clotting and fibrinolysis, cell migration, inflammatory processes, paralysis, etc.  At CAT, we take a multidisciplinary approach in the investigation of natural toxins that includes isolation and purification, studies of pharmacological actions, toxin structural determination and structure-function studies and its molecular and cell biology aspects. Several Brazilian institutions are involved with this endeavor that is centralized at the Butantan Institute. CAT also maintains active collaborations with foreign institutions in France, England, the USA, Germany, and Japan.

Technology Transfer

In Brazil, interaction between academia and industry often leaves much to be desired. There is little technological development outside of the Brazilian Universities, where an active, high quality basic scientific research environment trains qualified personnel, and stimulates brainpower in innovative thinking. A country may, if it so decides, build scientific and technical capabilities, but the maturation of such an effort requires time and continuity.

In order to reverse this picture, CAT has established a partnership with two Brazilian pharmaceutical enterprises. Within the scope of these partnerships, research findings obtained at CAT and evaluated for patent filing have been transferred to drug development in collaboration with some of the most important Brazilian pharmaceutical industries. A team of approximately 40 scientists and 25 graduated students and pos docs responsible for different tasks such as conducting animal trials, isolation and characterization of new compounds, molecular and cell biology, pharmacokinetic studies, among others, helped the early stage of drug development. Toxin-based drugs affecting blood clotting, the cardiovascular system, pain perception, anti-proliferate compounds and immune suppression are among those subjected to pre-clinical trials as a result of the partnership between CAT and Brazilian pharmaceutical industries.  

THE CENTER FOR APPLIED TOXINOLOGY (CAT), A PLATFORM FOR DRUG DISCOVERY IN BRAZIL (PART III)

ANTONIO C. M. CAMARGO

CAT/CEPID–Fapesp at the Instituto Butantan

Education

The educational activity at CAT aims at stimulating highly qualified professionals in the areas related to poisonous animals and their toxins so they can apply this knowledge to developing new pharmaceuticals and/or agrochemical products using biotechnological processes. Additionally, because we believe that scientific literacy is essential for a country economic development, together with Butantan, CAT has been actively involved with a toxin-related bioliteracy program that includes outreach programs and educational and cultural activities. “Museu Biológico”, for instance, exhibits both live and preserved specimens to about two hundred thousand visitors per year. The herpetological collection harbors some eighty thousand specimens of snakes and serves as a center for studies on distribution, taxonomy and evolution of snakes.

Together with Instituto Butantan, CAT has offered a variety of disciplines to some two thousand students a year.  For that, the CAT team relies on 19 senior investigators, students and on international collaborators invited to teach some specialized disciplines. Some disciplines offered at CAT include molecular biology in toxinology, biology of amphibians, laboratory animals, and others. The disciplines are grouped according to a field of application such as (i) education in R&D, (ii) accident prevention, (iii) biology of venomous animals, and (iv) systematic and evolution. Many disciplines are taught at different levels, for school children, teenagers and the general public, to undergraduate and graduate students, teachers and professionals. Additionally, CAT has published specialized books.

Through its partnerships and collaborations, the CAT initiative has opened new opportunities for innovation and for the young scientist interested in drug development. Indeed, when CAT was created 5 years ago, the Brazilian pharmaceutical industry was very skeptical about utilizing academic knowledge and technical-scientific know-how to generate prosperity and innovation. Today, the pharmaceutical companies have already hired some investigators and have shown interest in hiring an additional number of young PhDs.

At CAT, it is our earnest hope that our combined efforts will launch a new pharmaceutical R&D sector in Brazil.