November 13 is World Day of the Huntington’s disease, a neurodegenerative disease, caused by a hereditary genetic mutation, which causes cognitive impairment and motor and psychiatric problems. In Spain, it affects about four thousand people and, although it is a rare disease due to its incidence, it is the third most common neurodegenerative disease after Alzheimer’s and Parkinson’s.

Dr. José Manuel García Moreno, specialist in Neurology and expert in Movement Disorders, such as Parkinson’s or Huntington’s disease, we talks about this rare disease and how it affects the day to day of those who suffer from it.

In Spain there are about 4,000 affected by Huntington’s disease. Is it a rare disease, therefore?

Yes, it is considered a rare disease (ER). The problem is that there is no clear definition of ER. In general, we say that a disease is rare when it has a low prevalence in the population, but depending on the country they have different epidemiological definitions. Thus, in Europe, the disease that affects less than 1 person for every 2,000 inhabitants (50 / 100,000 inhabitants) is rare, but we believe that it is necessary for the different health systems and, especially the WHO, to give a consensual definition of what is understood by ER.

In the specific case of Huntington’s disease (HD), a prevalence of 5-10 cases / 100,000 inhabitants is estimated. This means, in effect, that in Spain it is very possible that there are at least 4000 cases. Worldwide, it is estimated that there may be between 350,000 and 700,000 people affected by the disease.

It is a disease caused by a genetic mutation. Do all people with that mutation develop the disease or does it just predispose?

No. Not everyone who inherits the mutation has HD. HD belongs to a group of genetic diseases called “trinucleotide expansion diseases.” These diseases are characterized because, although each member of the offspring has a 50% risk of inheriting the gene, whether the disease is triggered or not will depend on the size of that mutation.

In HD, a very small part of the HTT gene, called the CAG trinculeotide, repeats itself a greater number of times than in other healthy people and is what causes the mutation. In healthy people, CAG repeats itself in that gene 10 to 28 times. If a person has a number greater than 28 repeats, they will be a carrier of the mutation and can transmit it to their offspring. From that number 3 things can happen: If a person inherits only between 29 and 34 repetitions (the repetitions can increase from one generation to another), he will not suffer from the disease, but his descendants will have a greater risk of suffering from it. If what you inherit are between 35 and 39 CAG trinucleotide repeats, we know that some will suffer from it and others will not. Finally, patients who inherit a number greater than 40 repetitions will inherit and suffer the disease yes or yes.

What is Huntington’s disease: symptoms and possible treatments

What causes this mutation?

In the case of HD, the HTT gene is mutated, and this gene is responsible for the production of a protein called huntingtin, which is abnormal. This protein, which does not function well in neurons, causes these neurons to stop working properly and leads to the onset of HD.

Genetic tests to confirm if patients have the mutation. Is it easy to confuse it with other neurodegenerative diseases?

No. Today it is very difficult to confuse HD with another disease. If a patient presents compatible symptoms, and especially if he has a family history of a similar clinical picture, it is enough to do the genetic test to be able to diagnose it. No further tests are needed to diagnose the disease.

To date, there is no cure or effective treatment to stop cognitive decline, which causes death in 15-20 years. How is it treated then?

The early diagnosis of HD is very important because, although there is no curative treatment of the disease (as there is not for Alzheimer’s, nor for Parkinson’s, nor for many other diseases), there are numerous treatments to treat chorea (the movement disorder typical of the disease). There is also it to treat, the many psychiatric disorders that accompany the picture (depression, behavioral disorders, anxiety, insomnia, psychosis, obsessive compulsive disorder, impulse control disorder, etc.). An early treatment of the symptoms improves the quality of life of the patient and allows him to take care of himself as long as possible.

Locating the mutation before the disease develops, does it serve to slow or slow the disease?

No. It does not serve to delay the onset of the disease. The usefulness of the presymptomatic genetic diagnosis will depend greatly on the individual requesting it. Some people choose to get tested because it is preferable for them to know their genetic status because it will allow them to make informed decisions about their future. Others do it in order to make the determination as to whether or not to have children. Nowadays, what is called IVF with preimplantation diagnosis is possible, which allows to carry out in vitro fertilization with disease-free zygotes.

“Although there is no cure, early treatment improves the quality of life of the patient and allows him to be on his own for as long as possible”

As it is a disease that affects both movement and cognitive abilities, it must be multidisciplinary. What disciplines are involved?

The mainstay of HD treatment is pharmacological treatment, which is the one that has shown better control of the vast majority of the symptoms of the disease. Although the neurologist is the reference specialist in the disease, the collaboration of other professionals is always necessary, such as psychiatrists, clinical psychologists, speech therapists, physiotherapists, nutritionists, occupational therapists, neuropsychologists or geneticists.

How is the day to day of a Huntington patient?

The day to day will depend on many factors. On the one hand, being a carrier who has not developed the disease is not the same as being a carrier who has already developed it. It is not even the same to be a carrier of few repetitions, which may not develop the disease, to be a carrier of many repetitions, which you know you will surely develop. Then there are the patients who already have symptoms. It is not the same to be at the beginning of the disease than to have a highly evolved disease. Perhaps, if there is something that defines the day-to-day life of many patients, it is uncertainty and restlessness. The uncertainty of whether or not to have the genetic study done, the uncertainty of having or not having a partner, the uncertainty of whether or not to have offspring, the anxiety and unease of whether you will develop the disease and when that will happen, the unease of your uncertain future, the feeling of guilt of many patients for having transmitted the disease to their children, etc.

How is the coronavirus crisis affecting these patients?

The crisis generated by Covid-19 is affecting these patients in the same way as patients with Alzheimer’s, Parkinson’s or other neurodegenerative diseases, that is, through the deleterious effect of social isolation, fear and uncertainty, the closure of occupational therapy centers, patient associations, day centers, etc. Many of these patients, not being able to leave the house, having decreased their physical and mental activity, and not being able to interact with others, have significantly worsened. These are the collateral effects of the pandemic of which, today, we still do not have official data, but which, once all this happens, we will be able to assess in its proper measure.

Is there any promising treatment or research that gives hope to the sick and their families? What about gene therapies?

Yes, we are currently living a very hopeful moment, as gene therapies begin to be a reality. Specifically, in the case of HD, the most developed are a group of gene drugs called antisense oligonucleotides (ASO). What these drugs seek is to reduce the production of mutated huntingtin. An ASO is like a small DNA molecule that, by attaching itself to messenger RNA, prevents “the message of protein production carried by the DNA from being blocked” and with that, the cell will stop making the mutated protein. The hypothesis is that if we are able to reduce the amount of abnormal huntingtin in the brain, this may slow down the progression of HD. At the moment, we already know that both RG6042 (which is being studied by my team in the neurology service of the Virgen Macarena hospital) and WVE120102, which are the ASOs in the most advanced stage of research, reduce the amount of huntingtin in the brain of the patients. These are very recent data, since they have been published this year 2020. Now it remains to be known if the hypothesis is true and the reduction of mutated huntingtin in patients will mean a decrease in the progression of the disease.

“The ignorance of this disease and the absence of specialized centers or professionals makes patients feel ‘left out of the hand of God'”.

What are the main demands, both of those affected and of professionals, on this world day?

The problem with HD is that in most cases there are no specific health policies for it. These are diseases that, due to their rarity, do not have the social repercussion that others such as Alzheimer’s disease may have.

Many HD patients are not usually satisfied with the health care they receive and about 70% tend to feel that at least on one occasion they were not adequately treated by health personnel, mainly due to their ignorance of the disease. There are also no specialized centers where these patients can receive the support and care they need and many families report having difficulties accessing medicines.

Due to their disease, these patients often feel discriminated against not only in health care, but by society in general, as many patients suffer isolation and social distancing because their involuntary movements are mocked, they look at them on the street thinking that they are drunk… Many of these patients, in addition, lose job opportunities or have to leave work, at the moment of maximum maturity of the person, since this disease usually develops mainly around 40 years of age. Most of them have certificates of disability, but many of them have not been recognized the degree of disability that would correspond to the state of progression of the disease.

And the fact is that the ignorance that surrounds this disease and the absence of specialized centers or professionals, often makes these people and their families feel “left out of the hand of God”.