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Mintaka Medical Research Foundation

Mintaka's mission

Mintaka is a not-for-profit foundation which seeks to identify medical problems of the developing world for which high technology research can lead to simple and inexpensive solutions. The Foundation is currently involved in three projects, one connected with preventing infection of women and girls in developing countries by HIV/AIDS, one with the treatment of children with AIDS and one with trying to improve the treatment of uncontrolled, fatal bleeding of mothers after childbirth.   

Substances and devices developed under the Foundation’s sponsorship must be made available to the populations of developing countries without royalties, and where possible they should be manufactured in developing countries themselves. Safety testing of substances must however be carried out under government supervision, initially in the developed world.

1. Empowering women in the developing world to protect themselves from infection by HIV/AIDS

More than 50% of the current annual total of ca. 5 million infections by HIV in the developing world take place among women and young girls [1]. For many reasons, few are protected by condom use. To prevent infection, substances (wrongly but universally called ‘microbicides’) are urgently needed in the form of a cream or foam to be applied to the genital mucosa before sex. In what is currently its principal project, Mintaka is supporting the development of protein microbicides. The work is based on the molecule, developed by Mintaka's founders and their colleagues, known as PSC-RANTES [2, 3]. In brief:

• PSC-RANTES is among the most potent anti-HIV substances known.

• It is the only potential microbicide so far tested in the standard macaque model able, on its own, to protect every animal from infection [2, 4].

• Probably because of the unusual mechanism of action of PSC-RANTES, HIV seems to be almost uniquely prevented from  developing mutant strains that escape its action, unless they lose the characteristics normally essential for person-to-person infection [5].

• PSC-RANTES has some non-natural structures and can only be made by total chemical synthesis or semi-synthesis, which would make it too expensive for distribution in the developing world. However, our newer molecules in this series, found by a specially adapted variant of the method known as phage display [6], have all natural residues, and can be made by ordinary fermentation procedures. Calculation shows that that such proteins might possibly be made in multi-ton lots to so-called "food-grade GMP" standards for a few US cents a dose.

2. There are few children in rich countries infected by HIV and so there are no suitable drug formulations for the millions of infected children in poor countries

In conjunction with the School of Engineering in Geneva and the Connaught Clinic, Harare, Zimbabwe, Mintaka also has a pilot study addressing a problem in the administration of conventional tri-therapy drugs to children. So few children in the developing world have HIV/AIDS that Western companies have not put much effort into developing pediatric formulations. On the other hand there are over 2,000,000 children in the developing world currently living with HIV/AIDS. Millions more are already dead, including approximately half a million in 2005. Simple methods are being devised to fractionate adult anti-HIV drugs in ways that make it safe to administer them to children. Properly carried out, the effects on children with AIDS are dramatic.

Although she fits on a baby-weighing scale, this little girl is 3 years old! She will gain 2 kg per month if she can receive antiviral drugs at the correct doses. [Photo R. Lüthy, Connaught Clinic]

3. Bleeding after childbirth is the largest single cause of death of the mother

Finally, Mintaka is studying a possible need to create heat-stable forms of the hormone oxytocin for the management of severe haemorrhage after childbirth, the largest cause of maternal mortality worldwide [7]. Even leaving aside the fact that in tropical countries some labour and delivery rooms reach temperatures around 45°C, the need for a cold, or cool, chain is a handicap for oxytocin treatment and favours the use of small-molecule drugs which might otherwise be less appropriate.

1. Lederman, M.M., Offord, R.E. and Hartley, O. Microbicides and other topical strategies to prevent vaginal transmission of HIV. Nature Reviews Immunology 2006 (in press) and references cited therein.

2. Lederman, M.M., Veazey, R.S. Offord,. R.E., Mosier, D.M., Dufour, J., Mefford, M., Piatak, M., Lifson, J.D., Salkowitz, J.R., Rodriguez, B., Blauvelt, A, and Hartley, O. Prevention of vaginal SHIV transmission in rhesus macaques through inhibition of CCR5. Science 2004 306 485-487

3. Hartley O, Gaertner H, Wilken J, Thompson D, Fish R, Offord R et al. Medicinal chemistry applied to a synthetic protein: Development of highly potent HIV entry inhibitors. Proc. Natl Acad Sci USA 2004 101, 16460-16465

4. Lederman M.M., et al. abstract for the meeting ‘Microbicides 2006’ Cape Town April 23-26, 2006

5. Mosier, D. et al. abstract for the meeting ‘Microbicides 2006’ Cape Town April 23-26, 2006

6. Hartley, O., Dorgham, K., Cerini, F., Gaertner, H., Offord, R. E., Gorochov, G et al. Human immunodeficiency virus type 1 entry inhibitors selected on living cells from a library of phage chemokines J Virol 2003 77, 6637-6644

7. World Health Organization: Making Pregnancy Safer (December 2000). Available at http://www.who.int/gb/ebwha/pdf_files/EB107/ee26.pdf  [6 pages]. Accessed March 11, 2006.