Drug found efficient in incurable muscle disease

Huntington's disease is a severe muscle disease that slowly degenerates muscles and cognitive functions over time. There is no cure, but a study with an existing drug performed by the University of Texas shows that we might be able to slow the disease down, and protect the brain cells that are involved with the disease. While the compound has not yet been tested on humans, patients may be given more years with good life quality when it eventually finds its way to the clinic.

Experiments
When a drug called dantrolene, a muscle relaxant, was used in a mouse model of huntington's, the researchers found it slowed down the progression of the disease. Mice seemed to keep control over their muscles when treated with the drug. While other drugs are able to alleviate some of the uncontrolled muscle movements typical for huntington's, it does not provide protection against the progressive damaging of brain cells, which are called neurons. Dantrolene was found to protect neurons from damage, which indicates it may be more effective at slowing down the progression of the disease. None of the currently used drugs can protect the neurons from dying, while reducing the symptoms.

The drug
Dantrolene works by decreasing the amount of calcium inside the cell. Calcium ions are needed to generate excitation, which in the case of neurons is used to produce a signal. The neuronal function depends on where the signal is going to. When calcium signalling is overactivated, which just happens to a characteristic of Huntington's, then this can cause damage, knowns as excitotoxicity. By keeping the calcium levels down, this overexcitation does not occur, or is at least slowed down. In muscles, calcium works as an agent to induce contraction, which explains dantrolene's original function as a muscle relaxant.

Structural formula of dantrolene.

Pathology of huntington's

The striatum.

In Huntington's, a specific group of neurons is being targeted for degeneration: the so-called medium spiny neurons, located in a brain area called the striatum. They are involved with coordinating movement, which explains the symptoms. It all starts with a mutation in the huntingtin gene, which codes for a protein with the same name. The dysfunctional protein will eventually start causing the aforementioned problems, generally around middle age. While the complete mechanism is not fully understood, it is thought that huntingtin can act as an anti-apoptotic agent. That basically means the protein prevents the cell from killing itself.

Outlook
By showing that dantrolene can improve typical huntington's symptoms in mice, we may soon have a new treatment for this severe muscle disease. However, it all depends on how actual human patients will respond to the treatment. Regardless, the mechanism of dantrolene's function reveals that we can try similar drugs that also stabilize intracellular calcium levels. This method of action could be key to developing an actual cure in the future, that prevents neurons from getting damaged. Earlier, it was found that melatonin, what the body uses to make us sleepy, can also play a role in treating huntington's. It functions by a different mode of action, which may work synergistically when combined with dantrolene.