Sugar for AIDS – A simple solution for a complex problem?

Study of a rare genetic disease has shown some promise for a safe and low-cost remedy for the HIV/AIDS problem. Scientists at Meharry Medical College School of Medicine has found that cells affected by Niemann-Pick Type C (NPC) are unable to release HIV, suggesting these cells would not spread the virus. Niemann-Pick Type C or NPC is a disease caused by hereditary incorrect genetic code that prevents transport of lipid molecules (such as cholesterol) across cell membrane thus leading to huge accumulation of fatty substances inside cell which ultimately damages organs like liver, spleen and brain causing death. This cholesterol withholding capacity is supposed to have stopped the virus from replicating and spreading out.

AIDS is a killer disease in the world today that is caused by Human Immunodeficiency Virus or HIV. According to an estimate by UNAIDS around 30.8 million adults and 2 million children were living with HIV at the end of 2007. During the same year the number of newly infected persons was 2.7 million and 2 million deaths from AIDS had been reported. The available treatment for AIDS patients is called antiretroviral (ARV) therapy and is said to increase life-expectancy of HIV+ people. But it is too costly – a report published in International Conference on AIDS, 1998 puts the global economic burden for ARV therapy at US$36.5 billion annually. Given that about 95% of global total of HIV infected persons are from developing countries we can easily understand the impact that this disease produces on the poor economies (Africa was estimated to bear 66% of the global cost). Hence any cost-effective solution to the problem will relieve the developing countries from huge economic stress thus allowing them to divert the resources to address other developmental issues.

But before getting into the detail of the promising remedy first let us have a broad idea about how HIV spreads inside a human body. HIV has three structural parts – a coat of fatty substance with seventy two protein spikes as outer envelop, a protein matrix inside the envelop and the viral core contained in the matrix. The viral core holds the genetic materials and the enzymes required for the replication. Like any other virus HIV is inanimate outside a cell, but sticks to a cell which has a certain protein (called CD4) on its surface. Once it is stuck to the membrane, through a chemical process it injects its genetic materials inside the cell where they take up the control of the molecular machinery from the native genetic materials and produce the substances required for its replication. These viral substances are transported to the cell membrane where they assemble to a new virus and bud off to infect a new cell. Research has found that for HIV assembly and budding it requires a huge supply of cholesterol within the cell and the delivery of the same to the assembly site on cell membrane. HIV ensures this supply and delivery by influencing the cellular process that controls cholesterol through its genetic materials (see also). This helps to explain higher risk of cardiovascular disease among the HIV+ patients. Scientists have also found that when HIV-infected cells were treated with an agent that increased cholesterol removal, infectivity of HIV was reduced by around 80% when compared with untreated cells. NPC afflicted cells, in the above case, stop spreading of HIV by preventing transportation of cholesterol to the cell membrane.

This gives stronger indication of the importance of cholesterol lowering drugs in the treatment of HIV+ people. Scientists have actually reported a decrease in viral levels and increase in T-cell counts among AIDS patients after using Statins on them, which are widely used to reduce the risk of heart disease. Probably the cheapest and most safe agent for cholesterol depletion from cells is a class of sugar molecules called cyclodextrins. Studies have been performed to understand its effectiveness in controlling cellular cholesterol content, but never has been prescribed or used as a medicine. However it finds wider application in medicine preparation, food preservation, etc. So when Ms. Hempel’s desperate search for a potential remedy for her NPC afflicted twin daughters (Addi and Cassi) led her to cyclodextrins she was quick to realize how important it was to bring different scientists, working with cyclodextrins for different cholesterol related diseases, within a single platform of collaboration. Until then research on remedial use of cyclodextrins was sparse and sporadic. During the same time Dr. James Hildreth at Meharry Medical College was tossing with an idea of testing cyclodextrin as a HIV preventive agent, basing his hypothesis on the finding that cholesterol is important for spreading of HIV. Together they teamed up and started networking to impart momentum to cyclodextrin research. They sought for FDA’s permission to give the girls cyclodextrin infusion and recently got the nod. The girls are reported to respond positively to the chemical and no side-effect has been observed as yet, but the scientific community is willing to maintain a vigilant eye on the case. In the meantime test results on laboratory animals and cultured cells are indicating strongly the effectiveness of cyclodextrins as a remedy for AIDS and NPC.

This is not the end of the story but only the start of the journey. As Ms. Hemple stated “We’re proving the safety of this compound…I definitely feel like Addi and Cassi are leading the way here, not only for NPC kids, but potentially for AIDS patients.” Hence, I believe, we can be hopeful of a safe and low-cost cure for the dreaded disease in a near future.