HIV AIDS

Fasting could slow the development of a common type of childhood leukaemia

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Fasting can slow the development of one of the most common forms of childhood leukaemia, new research has found.

Based on tests in mice, going without food on a regular schedule was enough to halt the progress of two types of acute lymphoblastic leukaemia (ALL), and there’s hope that the findings could be used to develop treatments for cancer in humans, too.

ALL is caused by the body overproducing immature white blood cells called lymphoblasts that gradually replace healthy ones – and while the cancer does occur in adults, it most commonly occurs in children.

But when mice with ALL were restricted in their eating patterns, researchers from the University of Texas Southwestern Medical Centre noticed a significant drop-off in the disease’s effects. 

“We found that in models of ALL, a regimen consisting of six cycles of one day of fasting followed by one day of feeding completely inhibited cancer development,” says lead researcher Chengcheng Zhang.

“Mice in the ALL model group that ate normally died within 59 days, while 75 percent of the fasted mice survived more than 120 days without signs of leukaemia.”

To test how fasting could be used to stop the disease, the researchers used fluorescent, coloured proteins to keep track of the cancer cells.

After seven weeks, virtually no cancerous cells were detected in the fasting mice, while an average of 68 percent of cells were found to be cancerous in the mice that hadn’t been fasting.

Part of the treatment’s success seems to be related to the hunger-inhibiting hormone leptin, which is created by fat tissue.

Previous research has shown that fasting can reduce leptin levels, and ALL patients often show weakened leptin receptor activity, so the researchers paid close attention to both factors during their study.

They found that intermittent fasting in mice increased leptin receptor activity, and they think this fact is significant in the success of their treatment.

“We found that fasting decreased the levels of leptin circulating in the bloodstream as well as decreased the leptin levels in the bone marrow,” explains Zhang. “These effects became more pronounced with repeated cycles of fasting.”

“After fasting, the rate at which the leptin levels recovered seemed to correspond to the rate at which the cancerous ALL cells were cleared from the blood,” he adds.

While fasting was capable of stopping the development of ALL, the technique wasn’t as effective against another type of blood cancer that’s more common in adults, called acute myeloid leukaemia (AML).

In tests with a mouse model of AML, the activity of leptin receptors was unaffected by fasting, which could explain why restricted eating doesn’t seem to help against this different form of leukaemia. 

Of course, these tests have so far only been run on mice, so there’s no guarantee that the same results would be seen in people.

But if scientists are able to develop a similar treatment for humans with ALL, there’s one big advantage to this approach – deliberately skipping meals doesn’t involve taking any drugs, so clinical trials can start sooner without any extensive testing of pharmaceuticals.

The researchers are now keen to test their findings further, with a view to ultimately figuring out how to simulate fasting mechanisms in the body, so that patients with the disease don’t have to give up food to get better.

“It will be important to determine whether ALL cells can become resistant to the effects of fasting,” says Zhang.

“It also will be interesting to investigate whether we can find alternative ways that mimic fasting to block ALL development.”

The research has been published in Nature Medicine.

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A new antibody therapy appears to have permanently blocked HIV infection in monkeys

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A new type of antibody therapy appears to have completely blocked the primate equivalent of HIV in infected monkeys.

More than two years after the treatment, the monkeys are now drug free, have no symptoms, and there are almost no traces of the virus in their systems. The results are so impressive that clinical trials have already begun with human patients in the US.

“We have good reasons to believe that the therapy will work similarly in humans,” said lead researcher Lutz Walter from the German Primate Centre in Göttingen. “It would be a breakthrough for the future treatment of HIV patients.”

In the trial, rhesus macaques infected with simian immunodeficiency virus (SIV) – the primate version of HIV – were given a standard antiretroviral drug for 90 days, before being treated with an antibody called Vedolizumab for 23 weeks.

After completing the therapy, all monkeys showed sustained control of the infection, and there were almost no traces of the virus in their blood or gastro-intestinal tissues.

Impressively, two years later, the “viral load remained low, the immune system intact, and the rhesus macaques healthy”, a press release explains. The monkeys, for now at least, are in “sustained remission“.

“This finding could become a blueprint for an alternative therapy for HIV, which could make it so someone would not need to continuously take antiretroviral drugs,” said one of the researchers, Aftab Ansari, from Emory University School of Medicine and Yerkes National Primate Research Centre in the US. “It could also help us craft more effective vaccines.”

Once HIV infects someone, it immediately hides in their gut, hijacking a group of immune cells called CD4+ T-cells and using them to replicate itself and spread around the body. 

Antiretroviral drugs are already the most common form of treatment for patients with HIV, and taken regularly, they can help to keep this infection under control for decades . But they never remove HIV from the body altogether, so they have be taken permanently, and often cause side effects such as chronic inflammation, poisoning symptoms, and accelerated ageing.

That’s why researchers are trying to combine this approach with the use of antibodies, to develop a treatment that’s longer lasting.

Antibodies are a specific type of protein that our bodies produce in response to a certain antigen. They’re the proteins used in vaccines that tell our immune systems “Hey, I recognise this virus and it’s not good” – and researchers have spent years actively trying to develop antibodies that take down HIV.

But although there have been impressive results in the past, they’ve all been short-lived, and required ongoing injections of antibodies, because HIV is a master at hiding and disguising itself in its hosts.

Which is why this new approach is so promising.

“The aim of the study was to find a new therapeutic approach for the treatment of infections with immunodeficiency viruses, which would permanently prevent the proliferation of the viruses even after only temporarily application,” said Walter.

To figure this out, the team took 18 rhesus macaques infected with SIV and gave all of them antiretrovirals for 90 days, before giving 11 of them Vedolizumab every three weeks, and seven of them a generic antibody to serve as a control group.

Three of the monkeys in the treatment group were discounted from the study because their immune system fought back against Vedolizumab, but the other eight went on to have the virus pretty much erased from their system – while still maintaining healthy levels of T-cells in the body. This means the drug wasn’t just wiping out the immune system.

Barton F. Haynes, a Duke University immunologist who wasn’t involved with the study, told the LA Times that the antibody “allowed animals to control the infection” on their own. “That’s what was tantalising and surprising.”

Even better, Vedolizumab is already used in humans in Europe and the US to treat inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis, so it doesn’t need to go through the extensive safety testing that most new drugs would need to.

The antibody works by attacking a specific receptor on T-cells that are known to be susceptible to HIV infection – in inflammatory bowel diseases this helps to calm down an over-active immune response. And in monkeys with SIV, it seems to wipe out all the T-cells that HIV is hiding in, while leaving healthy ones intact.

More research is needed to be done now to verify exactly what Vedolizumab is doing to infected T-cells, and extensive clinical trials will have to take place before we know whether this works in humans.

But so far, it’s looking pretty promising. And Phase I clinical trials testing the same combination of Vedolizumab and antiretrovirals in 15 HIV-infected humans have already begun in the US, with the researchers looking to extend them to more countries soon.

The research has been published in Science. 

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Union Cabinet approves amendments to HIV and AIDS (Prevention and Control) Bill, 2014

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The Union Cabinet under the chairmanship of Prime Minister Narendra Modi has given its approval to introduce official amendments to the HIV and AIDS (Prevention and Control) Bill, 2014 which has been drafted to safeguard the rights of people living with HIV and affected by HIV.

The Bill seeks to address HIV-related discrimination, strengthen the existing programme by bringing in legal accountability and establish formal mechanisms for inquiring into complaints and redressing grievances. The Bill seeks to prevent and control the spread of HIV and AIDS, prohibits discrimination against persons with HIV and AIDS, provides for informed consent and confidentiality with regard to their treatment, places obligations on establishments to safeguard rights of persons living with HIV and create mechanisms for redressing complaints. The Bill also aims to enhance access to health care services by ensuring informed consent and confidentiality for HIV-related testing, treatment and clinical research.

The Bill lists various grounds on which discrimination against HIV positive persons and those living with them is prohibited. These include the denial, termination, discontinuation or unfair treatment with regard to employment, educational establishments, health care services, residing or renting property, standing for public or private office, and provision of insurance (unless based on actuarial studies).  The requirement for HIV testing as a pre-requisite for obtaining employment or accessing health care or education is also prohibited.

Every HIV infected or affected person below the age of 18 years has the right to reside in a shared household and enjoy the facilities of the household. The Bill also prohibits any individual from publishing information or advocating feelings of hatred against HIV positive persons and those living with them. The Bill also provides for Guardianship for minors. A person between the age of 12 to 18 years who has sufficient maturity in understanding and managing the affairs of his HIV or AIDS affected family shall be competent to act as a guardian of another sibling below 18 years of age to be applicable in the matters relating to admission to educational establishments, operating bank accounts, managing property, care and treatment, amongst others.

The Bill requires that “No person shall be compelled to disclose his HIV status except with his informed consent, and if required by a court order”. Establishments keeping records of information of HIV positive persons shall adopt data protection measures. According to the Bill, the central and state governments shall take measures to prevent the spread of HIV or AIDS; provide anti-retroviral therapy and infection management for persons with HIV or AIDS; facilitate their access to welfare schemes especially for women and children; formulate HIV or AIDS education communication programmes that are age appropriate, gender sensitive, and non-stigmatizing; and lay guidelines for the care and treatment of children with HIV or AIDS. Every person in the care and custody of the state shall have right to HIV prevention, testing, treatment and counseling services. The Bill suggest that cases relating to HIV positive persons shall be disposed’ off by the court on a priority basis and duly ensuring the confidentiality.

There are no financial implications of the Bill. Most of the activities are being already undertaken or can be integrated within the existing systems of various Ministries under training, communication and data management, etc. The Bill makes provision for appointment of an ombudsman by state governments to inquire into complaints related to the violation of the Act and penal actions in case of non-compliance. The ombudsman need not be a separate entity, but any existing state government functionary can be deputed or given additional charge.

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