Novel drug proves effective against neglected tropical diseases

Researchers have developed a novel drug with the potential to kill a bacterium causing two of the most neglected tropical diseases that lead to blindness and severe disability and affect over 157 million people globally. River blindness is a disease caused by a parasitic worm -- Onchocerca volvulus -- that affects the skin and eyes of people leading generally to blindness, while elephantiasis refers to a parasitic infection that causes extreme swelling in the arms and legs.

The team showed that the drug called AWZ1066S is based on a molecule and is effective in killing Wolbachia the bacterium, which is behind the diseases.

Elephantiasis is caused by a Wolbachia-dependent parasitic worm similar to the one that causes river blindness. Thus, a cure for one could result in a cure for the other.

The new drug which can be taken orally does not upset the gut biome and also shortened the time-scale of treatment from weeks to days, as against antibiotics which is a long treatment process, lasting up to six weeks, the researchers said.

"Our team has already shown that removing the bacteria with antibiotics results in the death of the worm, but until now we were unaware of how the bacteria protected the parasite in the first instance," said a lecturer.

The team found that Wolbachia bacteria inside the worm acts as a "disguise" for the parasite, resulting in the immune system reacting to it in an ineffective way.

The bacteria protect the worm from the body's natural defences, but once the bacteria are removed with antibiotics, the immune system responds appropriately, releasing cells, called eosinophils, that kill the worm.

The findings showed that AWZ1066S has a faster kill rate compared with other known antibiotics tested against Wolbachia in vitro.

It can achieve maximum reduction of Wolbachia just after a day of drug exposure compared with the other antibiotics tested. Currently, there is no vaccine for river blindness, but if a candidate could be identified this may help boost the immune system ahead of antibiotic treatment and reduce the length of time patients have to take the drug, the lecturer said.

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Novel drug may help treat hair loss

Lab studies showed that the drug had dramatic stimulatory effect on human hair follicles

For people with receding hairlines, help may soon be on the way, as scientists have identified a drug — originally designed as a treatment for osteoporosis — that can stimulate hair growth.

In a study published , researchers  showed that the drug has a dramatic stimulatory effect on human hair follicles donated by patients undergoing hair transplantation surgery.

Currently only two drugs — minoxidil and finasteride — are available for treatment of male-pattern balding (androgenetic alopecia). However, both agents have moderate side effects and often produce disappointing hair regrowth results. The only other option available to patients is hair transplantation surgery.

Genetic analysis

Researchers sought to develop new ways to promote human hair growth with the hope of finding novel, well-tolerated agents for treating androgenetic alopecia. The approach was to first identify the molecular mechanisms of an old immunosuppressive drug, Cyclosporine A (CsA). Cyclosporine A has been commonly used since the 1980s as a crucial drug that suppresses transplant rejection and autoimmune diseases. However, it often has severe side-effects, the least serious - but most interesting - of which is that it enhances cosmetically unwanted hair growth.

The team carried out a full gene expression analysis of isolated human scalp hair follicles treated with CsA. This revealed that CsA reduces the expression of SFRP1, a protein that inhibits the development and growth of many tissues, including hair follicles. This identifies a completely novel mechanism of action of this old and widely used immunosuppressant.

The research also explains why CsA so often induces undesired hair growth in patients as it removes an inbuilt and potent molecular brake on human hair growth. The inhibitory mechanism is completely unrelated to CsA’s immunosuppressive activities, making SFRP1 a new and highly promising therapeutic target for anti-hair loss strategies.

Researchers found that a compound originally developed to treat osteoporosis, called WAY-316606, targets the same mechanism as CsA by specifically antagonising SFRP1. When they then treated hair follicles with WAY-316606, the unrelated agent also effectively enhanced human hair growth like CsA.

The external application of WAY-316606 or similar compounds to balding human scalp, he argued, may promote hair growth to the same magnitude as CsA or even better, but without its side effects.

New hopes

“We were able to conduct our experiments with scalp hair follicles that had generously been donated by over 40 patients and were then tested in organ cultures,” said the author. “This makes our research clinically very relevant, as many hair research studies only use cell culture. When the hair growth-promoting effects of CsA were previously studied in mice, a very different molecular mechanism of action was suggested; had we relied on these mouse research concepts, we would have been barking up the wrong tree,” he said.

“The fact this new agent, which had never even been considered in a hair loss context, promotes human hair growth is exciting because of its transitional potential: it could one day make a real difference to people who suffer from hair loss. Clearly though, a clinical trial is required next to tell us whether this drug or similar compounds are both effective and safe in hair loss patients” he added.

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