Huntington’s Disease could originate in the heart says study

Research reinforces the thesis that the disorder is not purely neurological

By Fábio de Castro

Agência FAPESP – Huntington’s Disease, long considered to be a purely neurological problem, doesn’t originate only in the brain. And according to many recent studies, the illness can first appear in organs and peripheral tissues and even non-neuronal cells.

A new study released by scientists from the Universidade de São Paulo (USP) and in partnership with the Universidade Federal de São Paulo (Unifesp) strengthened the thesis of the non-cerebral and non-neuronal origin of the disease, showing that the protein that causes Huntington’s disease can be found in the heart.

The study was presented in September at the World Conference on Huntington’s Disease, held in Australia, and published in a special supplement of Clinical Genetics magazine exclusively dedicated to the event.
According to the authors, the new perspective of a non-cerebral, non-neural origin of the disease suggests a new line of scientific research aimed toward finding early biomarkers of the disease to make early diagnosis possible along with more effective treatment and longer lifespans for patients.

The study comprises the doctoral thesis currently being written by Fernando Vagner Lobo Ladd at Unifesp as a FAPESP fellow. At the beginning of his research in 2009, Ladd already received the Prêmio José Carlos Prates, awarded by Unifesp for the best studies presented during the 12th Congress of the Post-graduate Morphology Program.

The thesis is being overseen by professor Antonio Augusto Coppi, head of the Stochastic Stereology and Chemical Anatomy Laboratory (LSSCA) in the Surgical Department of USP’s School of Veterinary Medicine and Zootechny (FMVZ), where the research is effectively being carried out.

According to Coppi, Huntington’s Disease can no longer be treated as a purely neurological disorder as it effects and even originates in many organs and peripheral tissues like the heart—as shown in the study—striated skeletal muscle fibers, bones, testicles, the pancreas, the immune system, the enteric nervous system and the cardiac system.

“There is a dogma among neurologists considering the brain to be the only place that this type of disease originates. But we know that 30% of patients with Huntington’s Disease die of heart problems and not neurological problems. This is why we’ve been doing studies to understand the chronology of the evolution of the disease and how it affects the heart,” Coppi told Agência FAPESP.

The study, performed on two-month old male mice, showed that huntingtin, the protein associated with the disease, can be found in non-nervous cells in the heart and is therefore not specific to neurons.

“In the animals studied, the illness caused hypertrophy in the heart and dysfunction in the sympathetic innervation of the organ. We believe that hypertrophy occurs in order to compensate for innervation failure. All this can lead to cardiac problems, explaining the high percentage of patients with the disease that die from heart problems as opposed to neurological ones,” he said.

Aside from debasing the dogma of an exclusively cerebral origin, Coppi says the new studies have shown that the illness arises not only in neurons, but also in non-neuronal cells.

“There are neurons in innumerous organs outside the brain, including the heart, intestine, pancreas, trachea, bladder and liver. But often the disease appears in non-neural cells but rather muscular fibers of the myocardium, testicular cells and bone marrow. This can cause patients to develop heart problems, testicular atrophy and osteoporosis, for example,” he explained.

In seeking out new biological markers that could anticipate diagnosis of the diseases, researchers are clearing the path for new treatments that could slow the manifestation of early symptoms or prolong patients’ lifespans. There is still no perspective of a cure for Huntington’s Disease.

According to Coppi, the most recent studies show that when a patient presents muscular or testicular atrophy along with progressive weight loss, these problems are rarely associated with the onset of a neurological disease.  

“Like cancer, Huntington’s Disease has a silent phase. The advantage of knowing if the problem could start in other organs is that we could be able to already reveal it in the silent phase. The sooner it is discovered, the greater the chance of treatment,” said Coppi.

The article Haemodynamic and design-based stereological assessment of the heart in 3-NP-induced mice, by Fernando Ladd and Antonio Augusto Coppi, can be read by subscribers of Clinical Genetics at http://onlinelibrary.wiley.com.