Hope on the horizon for treatment of neurodegenerative disease

Dr. Ruben Dagda responds to Huntington’s disease breakthrough, discusses Parkinson’s and Alzheimer’s research

Huntington's disease

Exciting news recently emerged from the UK announcing a new treatment for Huntington's disease.

Huntington's disease (HD) is an inherited genetic disease, and according to the National Institute of Neurological Disorders and Stroke (NINDS), more than 30,000 Americans have it.

The disease is caused by a mutation on the huntingtin gene (HTT), a protein found in many of the body's tissues with the highest levels of activity in the brain, including nerve cells. Individuals with the mutation will absolutely develop HD in their lifetimes, typically between the ages of 30 and 50, although a juvenile version of the disease occurs under age 20. Additionally, since the disease is caused by a single genetic mutation, children with one parent who has HD have a 50 percent chance of inheriting the genetic defect.

The huntingtin genetic mutation causes the DNA building blocks-cytosine, adenine and guanine (CAG)-to repeat more than normal, leading to symptoms that get progressively worse, including uncontrolled movements (chorea), impaired coordination, slurred speech, difficulty eating and swallowing, as well as changes in behavior, emotion, judgement and cognition. With no current cure or effective treatment at slowing or reversing the disease, patients usually die 15 to 20 years following diagnosis-a long, terrible struggle with each day a bit worse than the last.

But there is hope.

A research team out of the University College London has developed an experimental drug, which is injected into the spinal fluid and uses a gene silencing technique to lower the levels of huntingtin in the brain. Simply put, the drug kills the messenger within the DNA code (mRNA) to prevent creation of the damaged huntingtin proteins.

Researchers, including UNR Med Assistant Professor of Pharmacology Ruben Dagda, Ph.D., are calling this study a breakthrough in neurodegenerative diseases:

"I would say this is very promising. The particular drug, termed IONIS-HTTRx, shuts down the expression of all forms of mutant huntingtin without affecting normal huntingtin. This form of gene therapy should also work for treating other degenerative disease caused by a mutation in one gene, including many forms of spinocerebellar ataxia."

Is it possible that a cure is on the horizon for HD? Dr. Dagda is cautiously optimistic, emphasizing that long-term information is still needed before it can be claimed that a cure has been found.

"The jury is still out on whether it will reverse all or some of the symptoms of HD. Also, keep in mind this is not necessarily a cure, but a form of treatment for a chronic, degenerative disease. Even with this treatment, the patient will always express the mutant huntingtin gene. We will definitely know if this form of gene therapy can reverse symptoms in HD patients within five or six more years."

What about other neurodegenerative diseases such as Parkinson's (PD) and Alzheimer's (AD)? Would it be possible, as some UK researchers suggest, to use this technique on those as well?

"It's much more complicated for Parkinson's and Alzheimer's disease as the majority of cases have no known cause and are not caused by a mutation in a single gene. Unlike Huntington's disease, brain degeneration observed in AD and PD are caused by several proteins that aggregate."

However, Dr. Dagda's team is striving to better understand and, potentially, develop therapies for these debilitating diseases.

"For more than 14 years, my research has focused on understanding why neurons lose their neuronal connections, energy and ultimately die in patients with Parkinson's and Alzheimer's disease. My research group uses cell culture models, animal models of PD and AD, and analyzes the molecule signatures that are altered in postmortem human brain tissue. We have identified different compounds that can reverse the loss of neuronal connections and energy in neurons in chemical and animal models of PD."

Much like the research on Huntington's disease, Dr. Dagda's goal is to translate his team's work to clinical research within a few years and develop a disease-modifying treatment for Parkinson's disease in the future.  

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The University of Nevada, Reno School of Medicine is a community-based, research-intensive medical school with a statewide vision that has served Nevada for 50 years. The state's first public medical school, UNR Med fosters a healthy Nevada through excellence in medical education, medical care, research and community engagement, within a culture of respect, compassion and inclusion. Through targeted growth and investment in research, clinical services, education and outreach, UNR Med is improving the future of health care. For more information, visit our 50th anniversary website.